Cancer

Immune checkpoint inhibitors (ICIs) are at least as effective in patients with advanced non–small cell lung cancer (NSCLC) and mild preexisting interstitial lung disease (ILD) as in those without ILD. However, the risk of checkpoint inhibitor pneumonitis (CIP) is higher in patients with the dual diagnoses and they need careful monitoring when introducing an ICI, a systematic review and meta-analysis indicated.

“Patients with preexisting ILD, especially symptomatic ILD, are frequently excluded from clinical trials so almost all the patients [we analyzed] were diagnosed with mild preexisting ILD,” said Yuan Cheng, MD, Peking University First Hospital, Beijing, China.

“At this stage, we think that mild ILD is not a contraindication to the use of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) treatment for patients with NSCLC but whether ICIs can be used in patients with moderate to severe ILD needs further study,” she added.

The study was published online Jan. 10 in the journal CHEST.
 

Ten studies

A total of 179 patients from 10 studies were included in the review and meta-analysis. Among these, six were retrospective case-control studies, one was a retrospective noncontrolled study and three were prospective, noncontrolled clinical trials. “All the included studies were from East Asian countries,” the authors noted.

Preexisting ILD was diagnosed by use of CT or high-resolution CT. The mean age of patients was 71 years (range, 33-85 years), 87% were male and 96% of the cohort had a history of smoking. Approximately one-quarter of patients with ILD had usual interstitial pneumonitis (UIP); about the same percentage had possible UIP; one-third were diagnosed with inconsistent UIP; 14% had nonspecific interstitial pneumonia (NSIP); and 6% had indeterminate UIP.

Patients received ICIs either as first-, second-, or third-line or higher therapy and all were treated with ICI monotherapy by way of either nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq). About 10% of patients had a PD-L1 tumor proportion score (TPS) of less than 1%, one-quarter had a PD-L1 TPS of 1%-49%, and approximately two-thirds had a TPS of 50% or greater.
 

Objective response rates

Some 35% of patients with both NSCLC and preexisting ILD achieved an objective response rate (ORR) to ICI therapy and almost two-thirds of patients achieved disease control. However, there was considerable heterogeneity in ORRs between the studies where it ranged from 5.9% to 70%, the authors cautioned.

On meta-analysis, the pooled ORR was 34% (95% confidence interval, 20%-47%) but again, with significant heterogeneity (I2 = 75.9%). However, on meta-analysis of eligible studies, patients with NSCLC who had preexisting ILD were 99% more likely to achieve an ORR compared to those without ILD (odds ratio, 1.99; 95% CI, 1.31-3.00), the investigators pointed out.

The disease control rate (DCR) also varied considerably between studies from a low of 33.3% to a high of 100%, they added. On meta-analysis, the pooled DCR was 66% (95% CI, 56%-75%). “Meanwhile, in patients without preexisting ILD, the crude ORR and pooled ORR were 24.3% and 24% (95% CI, 17%-31%), respectively” – again with significant heterogeneity between studies (I2 = 87.4%).

In contrast to the ORR, there was no difference in the DCR between the two groups, with no evidence of heterogeneity. There were no significant differences between the two groups in either median progression-free survival (PFS) or overall survival (OS). In patients with NSCLC and preexisting ILD, median PFS ranged from 1.4 to 8 months whereas median OS ranged from 15.6 to 27.8 months.

For those without preexisting ILD, the median PFS ranged from 2.3 to 8.1 months while median OS ranged from 17.4 to 25.5 months.
 

ICI safety

In patients with NSCLC and preexisting ILD, the incidence of immune-related adverse events (irAes) of any grade was 56.7%, whereas the incidence of irAEs grade 3 and higher was 27.7%. “Among the 179 patients included in the studies, 45 developed any grade of CIP, corresponding to a crude incidence of 25.1%,” the authors noted – very similar to the pooled incidence of 27% on meta-analysis.

The pooled incidence of grade 3 and higher CIP in the same group of patients was 15%. The median time from initiation of ICIs to the development of CIP ranged from 31 to 74 days, but 88% of patients who developed CIP improved with appropriate treatment. In patients with NSCLC who did not have ILD, the pooled incidence of CIP was 10% (95% CI, 6%-13%), again with significant heterogeneity between studies (I2 = 78.8%). “Generally, CIP can be managed through ICI discontinuation with or without steroid administration,” the authors noted.

However, even if most CIP can be easily managed, “the incidence of severe CIP is higher [in NSCLC patients with preexisting ILD] than in other populations,” Dr. Chen observed. “So patients with preexisting ILD should be closely monitored during ICI therapy,” she added.

Indeed, compared with patients without preexisting ILD, grade 3 or higher CIP in patients with the dual diagnosis was significantly higher at an OR of 3.23 (95%, 2.06-5.06), the investigators emphasized.

A limitation to the review and systematic meta-analysis included the fact that none of the studies analyzed were randomized clinical trials and most of the studies were retrospective and had several other shortcomings.
 

Umbrella diagnosis

Asked to comment on the review, Karthik Suresh, MD, associate professor of medicine, Johns Hopkins University, Baltimore, pointed out that ILD is really an “umbrella” diagnosis that a few hundred diseases fit under, so the first question he and members of his multidisciplinary team ask is: What is the nature of the ILD in this patient? What is the actual underlying etiology?

It could, for example, be that the patient has undergone prior chemotherapy or radiation therapy and has developed ILD as a result, as Dr. Suresh and his coauthor, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, pointed out in their paper on how to approach patients with preexisting lung disease to avoid ICI toxicities. “We’ll go back to their prior CT scans and can see the ILD has been there for years – it’s stable and the patient’s lung function is not changing,” Dr. Suresh related to this news organization.

“That’s a very different story from a [patients] whom there are new interstitial changes, who are progressing and who are symptomatic,” he noted. Essentially, what Dr. Suresh and his team members want to know is: What is the specific subdiagnosis of this disease, how severe is it, and is it progressing? Then they need to take the tumor itself into consideration.

“Some tumors have high PD-L1 expression, others have low PD-L1 expression so response to immunotherapy is usually very different based on tumor histology,” Dr. Suresh pointed out. Thus, the next question that needs to be addressed is: What is the expected response of the tumor to ICI therapy? If a tumor is exquisitely sensitive to immunotherapy, “that changes the game,” Dr. Suresh said, “whereas with other tumors, the oncologist might say there may be some benefit but it won’t be dramatic.”

The third risk factor for ICI toxicity that needs to be evaluated is the patient’s general cardiopulmonary status – for example, if a patient has mild, even moderate, ILD but is still walking 3 miles a day, has no heart problems, and is doing fine. Another patient with the same severity of disease in turn may have mild heart failure, be relatively debilitated, and sedentary: “Performance status also plays a big role in determining treatment,” Dr. Suresh emphasized.

The presence of other pulmonary conditions such as chronic obstructive pulmonary disease – common in patients with NSCLC – has to be taken into account, too. Lastly, clinicians need to ask themselves if there are any alternative therapies that might work just as well if not better than ICI therapy for this particular patient. If the patient has had genomic testing, results might indicate that the tumor has a mutation that may respond well to targeted therapies. “We put all these factors out on the table,” Dr. Suresh said.

“And you obviously have to involve the patient, too, so they understand the risks of ICI therapy and together we decide, ‘Yes, this patient with ILD should get immunotherapy or no, they should not,’ “ he said.  

The study had no specific funding. The study authors and Dr. Suresh have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors (ICIs) are at least as effective in patients with advanced non–small cell lung cancer (NSCLC) and mild preexisting interstitial lung disease (ILD) as in those without ILD. However, the risk of checkpoint inhibitor pneumonitis (CIP) is higher in patients with the dual diagnoses and they need careful monitoring when introducing an ICI, a systematic review and meta-analysis indicated.

“Patients with preexisting ILD, especially symptomatic ILD, are frequently excluded from clinical trials so almost all the patients [we analyzed] were diagnosed with mild preexisting ILD,” said Yuan Cheng, MD, Peking University First Hospital, Beijing, China.

“At this stage, we think that mild ILD is not a contraindication to the use of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) treatment for patients with NSCLC but whether ICIs can be used in patients with moderate to severe ILD needs further study,” she added.

The study was published online Jan. 10 in the journal CHEST.
 

Ten studies

A total of 179 patients from 10 studies were included in the review and meta-analysis. Among these, six were retrospective case-control studies, one was a retrospective noncontrolled study and three were prospective, noncontrolled clinical trials. “All the included studies were from East Asian countries,” the authors noted.

Preexisting ILD was diagnosed by use of CT or high-resolution CT. The mean age of patients was 71 years (range, 33-85 years), 87% were male and 96% of the cohort had a history of smoking. Approximately one-quarter of patients with ILD had usual interstitial pneumonitis (UIP); about the same percentage had possible UIP; one-third were diagnosed with inconsistent UIP; 14% had nonspecific interstitial pneumonia (NSIP); and 6% had indeterminate UIP.

Patients received ICIs either as first-, second-, or third-line or higher therapy and all were treated with ICI monotherapy by way of either nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq). About 10% of patients had a PD-L1 tumor proportion score (TPS) of less than 1%, one-quarter had a PD-L1 TPS of 1%-49%, and approximately two-thirds had a TPS of 50% or greater.
 

Objective response rates

Some 35% of patients with both NSCLC and preexisting ILD achieved an objective response rate (ORR) to ICI therapy and almost two-thirds of patients achieved disease control. However, there was considerable heterogeneity in ORRs between the studies where it ranged from 5.9% to 70%, the authors cautioned.

On meta-analysis, the pooled ORR was 34% (95% confidence interval, 20%-47%) but again, with significant heterogeneity (I2 = 75.9%). However, on meta-analysis of eligible studies, patients with NSCLC who had preexisting ILD were 99% more likely to achieve an ORR compared to those without ILD (odds ratio, 1.99; 95% CI, 1.31-3.00), the investigators pointed out.

The disease control rate (DCR) also varied considerably between studies from a low of 33.3% to a high of 100%, they added. On meta-analysis, the pooled DCR was 66% (95% CI, 56%-75%). “Meanwhile, in patients without preexisting ILD, the crude ORR and pooled ORR were 24.3% and 24% (95% CI, 17%-31%), respectively” – again with significant heterogeneity between studies (I2 = 87.4%).

In contrast to the ORR, there was no difference in the DCR between the two groups, with no evidence of heterogeneity. There were no significant differences between the two groups in either median progression-free survival (PFS) or overall survival (OS). In patients with NSCLC and preexisting ILD, median PFS ranged from 1.4 to 8 months whereas median OS ranged from 15.6 to 27.8 months.

For those without preexisting ILD, the median PFS ranged from 2.3 to 8.1 months while median OS ranged from 17.4 to 25.5 months.
 

ICI safety

In patients with NSCLC and preexisting ILD, the incidence of immune-related adverse events (irAes) of any grade was 56.7%, whereas the incidence of irAEs grade 3 and higher was 27.7%. “Among the 179 patients included in the studies, 45 developed any grade of CIP, corresponding to a crude incidence of 25.1%,” the authors noted – very similar to the pooled incidence of 27% on meta-analysis.

The pooled incidence of grade 3 and higher CIP in the same group of patients was 15%. The median time from initiation of ICIs to the development of CIP ranged from 31 to 74 days, but 88% of patients who developed CIP improved with appropriate treatment. In patients with NSCLC who did not have ILD, the pooled incidence of CIP was 10% (95% CI, 6%-13%), again with significant heterogeneity between studies (I2 = 78.8%). “Generally, CIP can be managed through ICI discontinuation with or without steroid administration,” the authors noted.

However, even if most CIP can be easily managed, “the incidence of severe CIP is higher [in NSCLC patients with preexisting ILD] than in other populations,” Dr. Chen observed. “So patients with preexisting ILD should be closely monitored during ICI therapy,” she added.

Indeed, compared with patients without preexisting ILD, grade 3 or higher CIP in patients with the dual diagnosis was significantly higher at an OR of 3.23 (95%, 2.06-5.06), the investigators emphasized.

A limitation to the review and systematic meta-analysis included the fact that none of the studies analyzed were randomized clinical trials and most of the studies were retrospective and had several other shortcomings.
 

Umbrella diagnosis

Asked to comment on the review, Karthik Suresh, MD, associate professor of medicine, Johns Hopkins University, Baltimore, pointed out that ILD is really an “umbrella” diagnosis that a few hundred diseases fit under, so the first question he and members of his multidisciplinary team ask is: What is the nature of the ILD in this patient? What is the actual underlying etiology?

It could, for example, be that the patient has undergone prior chemotherapy or radiation therapy and has developed ILD as a result, as Dr. Suresh and his coauthor, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, pointed out in their paper on how to approach patients with preexisting lung disease to avoid ICI toxicities. “We’ll go back to their prior CT scans and can see the ILD has been there for years – it’s stable and the patient’s lung function is not changing,” Dr. Suresh related to this news organization.

“That’s a very different story from a [patients] whom there are new interstitial changes, who are progressing and who are symptomatic,” he noted. Essentially, what Dr. Suresh and his team members want to know is: What is the specific subdiagnosis of this disease, how severe is it, and is it progressing? Then they need to take the tumor itself into consideration.

“Some tumors have high PD-L1 expression, others have low PD-L1 expression so response to immunotherapy is usually very different based on tumor histology,” Dr. Suresh pointed out. Thus, the next question that needs to be addressed is: What is the expected response of the tumor to ICI therapy? If a tumor is exquisitely sensitive to immunotherapy, “that changes the game,” Dr. Suresh said, “whereas with other tumors, the oncologist might say there may be some benefit but it won’t be dramatic.”

The third risk factor for ICI toxicity that needs to be evaluated is the patient’s general cardiopulmonary status – for example, if a patient has mild, even moderate, ILD but is still walking 3 miles a day, has no heart problems, and is doing fine. Another patient with the same severity of disease in turn may have mild heart failure, be relatively debilitated, and sedentary: “Performance status also plays a big role in determining treatment,” Dr. Suresh emphasized.

The presence of other pulmonary conditions such as chronic obstructive pulmonary disease – common in patients with NSCLC – has to be taken into account, too. Lastly, clinicians need to ask themselves if there are any alternative therapies that might work just as well if not better than ICI therapy for this particular patient. If the patient has had genomic testing, results might indicate that the tumor has a mutation that may respond well to targeted therapies. “We put all these factors out on the table,” Dr. Suresh said.

“And you obviously have to involve the patient, too, so they understand the risks of ICI therapy and together we decide, ‘Yes, this patient with ILD should get immunotherapy or no, they should not,’ “ he said.  

The study had no specific funding. The study authors and Dr. Suresh have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Immune checkpoint inhibitors (ICIs) are at least as effective in patients with advanced non–small cell lung cancer (NSCLC) and mild preexisting interstitial lung disease (ILD) as in those without ILD. However, the risk of checkpoint inhibitor pneumonitis (CIP) is higher in patients with the dual diagnoses and they need careful monitoring when introducing an ICI, a systematic review and meta-analysis indicated.

“Patients with preexisting ILD, especially symptomatic ILD, are frequently excluded from clinical trials so almost all the patients [we analyzed] were diagnosed with mild preexisting ILD,” said Yuan Cheng, MD, Peking University First Hospital, Beijing, China.

“At this stage, we think that mild ILD is not a contraindication to the use of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) treatment for patients with NSCLC but whether ICIs can be used in patients with moderate to severe ILD needs further study,” she added.

The study was published online Jan. 10 in the journal CHEST.
 

Ten studies

A total of 179 patients from 10 studies were included in the review and meta-analysis. Among these, six were retrospective case-control studies, one was a retrospective noncontrolled study and three were prospective, noncontrolled clinical trials. “All the included studies were from East Asian countries,” the authors noted.

Preexisting ILD was diagnosed by use of CT or high-resolution CT. The mean age of patients was 71 years (range, 33-85 years), 87% were male and 96% of the cohort had a history of smoking. Approximately one-quarter of patients with ILD had usual interstitial pneumonitis (UIP); about the same percentage had possible UIP; one-third were diagnosed with inconsistent UIP; 14% had nonspecific interstitial pneumonia (NSIP); and 6% had indeterminate UIP.

Patients received ICIs either as first-, second-, or third-line or higher therapy and all were treated with ICI monotherapy by way of either nivolumab (Opdivo), pembrolizumab (Keytruda), or atezolizumab (Tecentriq). About 10% of patients had a PD-L1 tumor proportion score (TPS) of less than 1%, one-quarter had a PD-L1 TPS of 1%-49%, and approximately two-thirds had a TPS of 50% or greater.
 

Objective response rates

Some 35% of patients with both NSCLC and preexisting ILD achieved an objective response rate (ORR) to ICI therapy and almost two-thirds of patients achieved disease control. However, there was considerable heterogeneity in ORRs between the studies where it ranged from 5.9% to 70%, the authors cautioned.

On meta-analysis, the pooled ORR was 34% (95% confidence interval, 20%-47%) but again, with significant heterogeneity (I2 = 75.9%). However, on meta-analysis of eligible studies, patients with NSCLC who had preexisting ILD were 99% more likely to achieve an ORR compared to those without ILD (odds ratio, 1.99; 95% CI, 1.31-3.00), the investigators pointed out.

The disease control rate (DCR) also varied considerably between studies from a low of 33.3% to a high of 100%, they added. On meta-analysis, the pooled DCR was 66% (95% CI, 56%-75%). “Meanwhile, in patients without preexisting ILD, the crude ORR and pooled ORR were 24.3% and 24% (95% CI, 17%-31%), respectively” – again with significant heterogeneity between studies (I2 = 87.4%).

In contrast to the ORR, there was no difference in the DCR between the two groups, with no evidence of heterogeneity. There were no significant differences between the two groups in either median progression-free survival (PFS) or overall survival (OS). In patients with NSCLC and preexisting ILD, median PFS ranged from 1.4 to 8 months whereas median OS ranged from 15.6 to 27.8 months.

For those without preexisting ILD, the median PFS ranged from 2.3 to 8.1 months while median OS ranged from 17.4 to 25.5 months.
 

ICI safety

In patients with NSCLC and preexisting ILD, the incidence of immune-related adverse events (irAes) of any grade was 56.7%, whereas the incidence of irAEs grade 3 and higher was 27.7%. “Among the 179 patients included in the studies, 45 developed any grade of CIP, corresponding to a crude incidence of 25.1%,” the authors noted – very similar to the pooled incidence of 27% on meta-analysis.

The pooled incidence of grade 3 and higher CIP in the same group of patients was 15%. The median time from initiation of ICIs to the development of CIP ranged from 31 to 74 days, but 88% of patients who developed CIP improved with appropriate treatment. In patients with NSCLC who did not have ILD, the pooled incidence of CIP was 10% (95% CI, 6%-13%), again with significant heterogeneity between studies (I2 = 78.8%). “Generally, CIP can be managed through ICI discontinuation with or without steroid administration,” the authors noted.

However, even if most CIP can be easily managed, “the incidence of severe CIP is higher [in NSCLC patients with preexisting ILD] than in other populations,” Dr. Chen observed. “So patients with preexisting ILD should be closely monitored during ICI therapy,” she added.

Indeed, compared with patients without preexisting ILD, grade 3 or higher CIP in patients with the dual diagnosis was significantly higher at an OR of 3.23 (95%, 2.06-5.06), the investigators emphasized.

A limitation to the review and systematic meta-analysis included the fact that none of the studies analyzed were randomized clinical trials and most of the studies were retrospective and had several other shortcomings.
 

Umbrella diagnosis

Asked to comment on the review, Karthik Suresh, MD, associate professor of medicine, Johns Hopkins University, Baltimore, pointed out that ILD is really an “umbrella” diagnosis that a few hundred diseases fit under, so the first question he and members of his multidisciplinary team ask is: What is the nature of the ILD in this patient? What is the actual underlying etiology?

It could, for example, be that the patient has undergone prior chemotherapy or radiation therapy and has developed ILD as a result, as Dr. Suresh and his coauthor, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, pointed out in their paper on how to approach patients with preexisting lung disease to avoid ICI toxicities. “We’ll go back to their prior CT scans and can see the ILD has been there for years – it’s stable and the patient’s lung function is not changing,” Dr. Suresh related to this news organization.

“That’s a very different story from a [patients] whom there are new interstitial changes, who are progressing and who are symptomatic,” he noted. Essentially, what Dr. Suresh and his team members want to know is: What is the specific subdiagnosis of this disease, how severe is it, and is it progressing? Then they need to take the tumor itself into consideration.

“Some tumors have high PD-L1 expression, others have low PD-L1 expression so response to immunotherapy is usually very different based on tumor histology,” Dr. Suresh pointed out. Thus, the next question that needs to be addressed is: What is the expected response of the tumor to ICI therapy? If a tumor is exquisitely sensitive to immunotherapy, “that changes the game,” Dr. Suresh said, “whereas with other tumors, the oncologist might say there may be some benefit but it won’t be dramatic.”

The third risk factor for ICI toxicity that needs to be evaluated is the patient’s general cardiopulmonary status – for example, if a patient has mild, even moderate, ILD but is still walking 3 miles a day, has no heart problems, and is doing fine. Another patient with the same severity of disease in turn may have mild heart failure, be relatively debilitated, and sedentary: “Performance status also plays a big role in determining treatment,” Dr. Suresh emphasized.

The presence of other pulmonary conditions such as chronic obstructive pulmonary disease – common in patients with NSCLC – has to be taken into account, too. Lastly, clinicians need to ask themselves if there are any alternative therapies that might work just as well if not better than ICI therapy for this particular patient. If the patient has had genomic testing, results might indicate that the tumor has a mutation that may respond well to targeted therapies. “We put all these factors out on the table,” Dr. Suresh said.

“And you obviously have to involve the patient, too, so they understand the risks of ICI therapy and together we decide, ‘Yes, this patient with ILD should get immunotherapy or no, they should not,’ “ he said.  

The study had no specific funding. The study authors and Dr. Suresh have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

It is indisputable that patients with newly diagnosed advanced non–small cell lung cancer (NSCLC) bearing mutations in the epidermal growth factor receptor (EGFR) pathway may benefit from targeted therapy with a tyrosine kinase inhibitor (TKI) directed against EGFR.

What’s less clear is whether monotherapy with an EGFR TKI or combination therapy with a TKI and chemotherapy, immunotherapy, monoclonal antibodies or other targeted agents is the preferred frontline strategy.

NSCLC guidelines from the National Comprehensive Cancer Network, for example, recommend that patients with EFGR mutations such as exon 19 deletion, discovered prior to first-line systemic therapy, should preferably received osimertinib (Tagrisso) or another TKI, such as erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) or dacomitinib (Vizimpro), or erlotinib with a VEGF inhibitor. For patients with EGFR mutations identified during first-line systemic therapy, NCCN recommends complete systemic therapy or interrupting it, followed by osimertinib as the preferred agent, or another TKI with or without a VEGF inhibitors.

Similarly, guidelines from the American Society of Clinical Oncology and Ontario Health recommend osimertinib monotherapy as a preferred first-line option for patients with L858R/exon 19 deletion EGFR mutations. Alternatives for patients for whom osimertinib is not available include gefitinib plus platinum/pemetrexed chemotherapy with maintenance pemetrexed, monotherapy with dacomitinib, or other targeted agents with or without VEGF inhibitors.

Combination or go it alone?

The guidelines are largely mute on the question of chemotherapy in this population, primarily because they have not caught up to clinical trial evidence, said Paul Wheatley-Price, MBChB, FRCP, MD, from the University of Ottawa Hospital Research Institute.

“There is recent data that looks quite promising on combining EGFR inhibitors with either chemotherapy or antiangiogenic drugs, but it’s too soon, I think, and while the trials are promising, there are still too many question marks over it to make it into the guidelines,” he said in an interview.

The question of frontline combinations vs. monotherapy in patients with advanced EGFR-mutated NSCLC was the subject of a recent “controversies in thoracic oncology” feature in the Journal of Thoracic Oncology, with Dr. Wheatley-Price and University of Ottawa colleague Sara Moore, MD, FRCPC, arguing that combining EGFR TKIs with either cytotoxic chemotherapy or antiangiogenic monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) receptor has been shown consistently to improve progression-free survival (PFS) and in some cases overall survival (OS).

“There is a consistent drop-off in patients who receive second-line therapy, highlighting the importance of using combination therapy in the first-line setting to ensure patients will be exposed to multiple available therapies that may prolong survival. Chemotherapy-based combinations lead to improved response rates which may be especially helpful in patients with a significant burden of disease,” they wrote.

The authors noted that, compared with patients with wild-type EGFR, patients with EGFR-mutated NSCLC had a doubling of response rates to chemotherapy with a platinum-based doublet in the IPASS trial, suggesting that EGFR-mutated tumors may be more chemosensitive.
 

Promising trials, old drug

“Chemotherapy and EGFR TKIs may have a synergistic effect through combined reduction in vascular endothelial growth factor (VEGF)–mediated angiogenesis, and with EGFR TKIs counteracting chemotherapy-induced up-regulation of downstream EGFR signaling,” they wrote.

The authors cited two studies, one from Japan, and one from India, both of which showed significant improvements in response rates, PFS, and OS with the combination of gefitinib plus carboplatin and pemetrexed chemotherapy with pemetrexed maintenance vs. carboplatin alone,

“Now of course we don’t use gefitinib as our first-line treatment. In Canada and the United States, we use osimertinib, so certainly the chemotherapy/TKI combination, while it looks quite promising, was compared to an old control arm,” Dr. Wheatley-Price said.

He noted that the phase 3 FLAURA2 trial, currently underway, will address the question of whether adding osimertinib to a chemotherapy doublet with pemetrexed plus either carboplatin or cisplatin can improve PFS in patients with EGFR-positive locally advanced or metastatic NSCLC, compared with osimertinib alone.

The authors acknowledged that chemotherapy adds toxicities, compared with the use of TKI monotherapy, but added that, “even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

VEGF plus EGFR

Adding a VEGF-targeted monoclonal antibody or TKI to and EGFR TKI has shown consistent PFS benefits in the NEJ026, ARTEMIS, RELAY, and ACTIVE trials, Dr. Moore and Dr. Wheatley-Price noted.

“In all four trials, resistance testing at the time of progression revealed similar rates of T790M mutation in both arms, highlighting the potential role of optimizing the sequence of therapy with use of second-line osimertinib among those with a T790M resistance mutation,” they wrote.

All four trials also showed higher rates of adverse events in the combination arms, but most, except for hypertension, were low grade, and in the RELAY trial the added toxicities did not significantly affect patient quality of life, they said.
 

Monotherapy advocated

Although in agreement that the combination of gefitinib and chemotherapy has both PFS and OS benefits compared with monotherapy alone, “these combinations are not applicable to real-life practice given their use of first-generation EGFR TKIs rather than third-generation EGFR TKI osimertinib,” wrote Sophie Stock-Martineau, MD, FRCPC from Hôpital Maisonneuve-Rosemont and the University of Montreal, and Frances A. Shepherd, MD, FRCPC from the Princess Margaret Cancer Centre in Toronto, in an article touting EGFR monotherapy.

They stated that until the results of FLAURA2 are available “osimertinib alone remains the current standard first-line therapy in metastatic EGFRm+ NSCLC.”

“The addition of an antiangiogenic agent to an EGFR TKI mildly prolongs PFS; however, it does not yet translate into survival benefit. Not only does it add more toxicity to patients, but it also adds cost, which is far from negligible,” they wrote.

Dr. Stock-Martineau and Dr. Shepherd also noted that two phase 2 trials comparing afatinib with the EGFR monoclonal antibody cetuximab (Erbitux) showed no PFS or OS benefits in patients with untreated EGFR-mutated NSCLC and were terminated for lack of efficacy.

In addition, clinical trials of combinations of EGFR TKIs with immune checkpoint inhibitors ­or MET inhibitors have failed to date to demonstrate survival benefits, the authors said.

“No trials have yet revealed PFS or OS benefit with osimertinib combinations. Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system. Combinations could potentially also worsen quality of life given their heightened toxicity profiles. Therefore, single-agent EGFR TKI, such as osimertinib, remains for now the standard of care in the first-line setting for advanced EGFRm+ NSCLC,” they concluded.

No funding sources for the articles were reported. All authors declared no conflicts of interest to disclose.

It is indisputable that patients with newly diagnosed advanced non–small cell lung cancer (NSCLC) bearing mutations in the epidermal growth factor receptor (EGFR) pathway may benefit from targeted therapy with a tyrosine kinase inhibitor (TKI) directed against EGFR.

What’s less clear is whether monotherapy with an EGFR TKI or combination therapy with a TKI and chemotherapy, immunotherapy, monoclonal antibodies or other targeted agents is the preferred frontline strategy.

NSCLC guidelines from the National Comprehensive Cancer Network, for example, recommend that patients with EFGR mutations such as exon 19 deletion, discovered prior to first-line systemic therapy, should preferably received osimertinib (Tagrisso) or another TKI, such as erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) or dacomitinib (Vizimpro), or erlotinib with a VEGF inhibitor. For patients with EGFR mutations identified during first-line systemic therapy, NCCN recommends complete systemic therapy or interrupting it, followed by osimertinib as the preferred agent, or another TKI with or without a VEGF inhibitors.

Similarly, guidelines from the American Society of Clinical Oncology and Ontario Health recommend osimertinib monotherapy as a preferred first-line option for patients with L858R/exon 19 deletion EGFR mutations. Alternatives for patients for whom osimertinib is not available include gefitinib plus platinum/pemetrexed chemotherapy with maintenance pemetrexed, monotherapy with dacomitinib, or other targeted agents with or without VEGF inhibitors.

Combination or go it alone?

The guidelines are largely mute on the question of chemotherapy in this population, primarily because they have not caught up to clinical trial evidence, said Paul Wheatley-Price, MBChB, FRCP, MD, from the University of Ottawa Hospital Research Institute.

“There is recent data that looks quite promising on combining EGFR inhibitors with either chemotherapy or antiangiogenic drugs, but it’s too soon, I think, and while the trials are promising, there are still too many question marks over it to make it into the guidelines,” he said in an interview.

The question of frontline combinations vs. monotherapy in patients with advanced EGFR-mutated NSCLC was the subject of a recent “controversies in thoracic oncology” feature in the Journal of Thoracic Oncology, with Dr. Wheatley-Price and University of Ottawa colleague Sara Moore, MD, FRCPC, arguing that combining EGFR TKIs with either cytotoxic chemotherapy or antiangiogenic monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) receptor has been shown consistently to improve progression-free survival (PFS) and in some cases overall survival (OS).

“There is a consistent drop-off in patients who receive second-line therapy, highlighting the importance of using combination therapy in the first-line setting to ensure patients will be exposed to multiple available therapies that may prolong survival. Chemotherapy-based combinations lead to improved response rates which may be especially helpful in patients with a significant burden of disease,” they wrote.

The authors noted that, compared with patients with wild-type EGFR, patients with EGFR-mutated NSCLC had a doubling of response rates to chemotherapy with a platinum-based doublet in the IPASS trial, suggesting that EGFR-mutated tumors may be more chemosensitive.
 

Promising trials, old drug

“Chemotherapy and EGFR TKIs may have a synergistic effect through combined reduction in vascular endothelial growth factor (VEGF)–mediated angiogenesis, and with EGFR TKIs counteracting chemotherapy-induced up-regulation of downstream EGFR signaling,” they wrote.

The authors cited two studies, one from Japan, and one from India, both of which showed significant improvements in response rates, PFS, and OS with the combination of gefitinib plus carboplatin and pemetrexed chemotherapy with pemetrexed maintenance vs. carboplatin alone,

“Now of course we don’t use gefitinib as our first-line treatment. In Canada and the United States, we use osimertinib, so certainly the chemotherapy/TKI combination, while it looks quite promising, was compared to an old control arm,” Dr. Wheatley-Price said.

He noted that the phase 3 FLAURA2 trial, currently underway, will address the question of whether adding osimertinib to a chemotherapy doublet with pemetrexed plus either carboplatin or cisplatin can improve PFS in patients with EGFR-positive locally advanced or metastatic NSCLC, compared with osimertinib alone.

The authors acknowledged that chemotherapy adds toxicities, compared with the use of TKI monotherapy, but added that, “even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

VEGF plus EGFR

Adding a VEGF-targeted monoclonal antibody or TKI to and EGFR TKI has shown consistent PFS benefits in the NEJ026, ARTEMIS, RELAY, and ACTIVE trials, Dr. Moore and Dr. Wheatley-Price noted.

“In all four trials, resistance testing at the time of progression revealed similar rates of T790M mutation in both arms, highlighting the potential role of optimizing the sequence of therapy with use of second-line osimertinib among those with a T790M resistance mutation,” they wrote.

All four trials also showed higher rates of adverse events in the combination arms, but most, except for hypertension, were low grade, and in the RELAY trial the added toxicities did not significantly affect patient quality of life, they said.
 

Monotherapy advocated

Although in agreement that the combination of gefitinib and chemotherapy has both PFS and OS benefits compared with monotherapy alone, “these combinations are not applicable to real-life practice given their use of first-generation EGFR TKIs rather than third-generation EGFR TKI osimertinib,” wrote Sophie Stock-Martineau, MD, FRCPC from Hôpital Maisonneuve-Rosemont and the University of Montreal, and Frances A. Shepherd, MD, FRCPC from the Princess Margaret Cancer Centre in Toronto, in an article touting EGFR monotherapy.

They stated that until the results of FLAURA2 are available “osimertinib alone remains the current standard first-line therapy in metastatic EGFRm+ NSCLC.”

“The addition of an antiangiogenic agent to an EGFR TKI mildly prolongs PFS; however, it does not yet translate into survival benefit. Not only does it add more toxicity to patients, but it also adds cost, which is far from negligible,” they wrote.

Dr. Stock-Martineau and Dr. Shepherd also noted that two phase 2 trials comparing afatinib with the EGFR monoclonal antibody cetuximab (Erbitux) showed no PFS or OS benefits in patients with untreated EGFR-mutated NSCLC and were terminated for lack of efficacy.

In addition, clinical trials of combinations of EGFR TKIs with immune checkpoint inhibitors ­or MET inhibitors have failed to date to demonstrate survival benefits, the authors said.

“No trials have yet revealed PFS or OS benefit with osimertinib combinations. Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system. Combinations could potentially also worsen quality of life given their heightened toxicity profiles. Therefore, single-agent EGFR TKI, such as osimertinib, remains for now the standard of care in the first-line setting for advanced EGFRm+ NSCLC,” they concluded.

No funding sources for the articles were reported. All authors declared no conflicts of interest to disclose.

It is indisputable that patients with newly diagnosed advanced non–small cell lung cancer (NSCLC) bearing mutations in the epidermal growth factor receptor (EGFR) pathway may benefit from targeted therapy with a tyrosine kinase inhibitor (TKI) directed against EGFR.

What’s less clear is whether monotherapy with an EGFR TKI or combination therapy with a TKI and chemotherapy, immunotherapy, monoclonal antibodies or other targeted agents is the preferred frontline strategy.

NSCLC guidelines from the National Comprehensive Cancer Network, for example, recommend that patients with EFGR mutations such as exon 19 deletion, discovered prior to first-line systemic therapy, should preferably received osimertinib (Tagrisso) or another TKI, such as erlotinib (Tarceva), afatinib (Gilotrif), gefitinib (Iressa) or dacomitinib (Vizimpro), or erlotinib with a VEGF inhibitor. For patients with EGFR mutations identified during first-line systemic therapy, NCCN recommends complete systemic therapy or interrupting it, followed by osimertinib as the preferred agent, or another TKI with or without a VEGF inhibitors.

Similarly, guidelines from the American Society of Clinical Oncology and Ontario Health recommend osimertinib monotherapy as a preferred first-line option for patients with L858R/exon 19 deletion EGFR mutations. Alternatives for patients for whom osimertinib is not available include gefitinib plus platinum/pemetrexed chemotherapy with maintenance pemetrexed, monotherapy with dacomitinib, or other targeted agents with or without VEGF inhibitors.

Combination or go it alone?

The guidelines are largely mute on the question of chemotherapy in this population, primarily because they have not caught up to clinical trial evidence, said Paul Wheatley-Price, MBChB, FRCP, MD, from the University of Ottawa Hospital Research Institute.

“There is recent data that looks quite promising on combining EGFR inhibitors with either chemotherapy or antiangiogenic drugs, but it’s too soon, I think, and while the trials are promising, there are still too many question marks over it to make it into the guidelines,” he said in an interview.

The question of frontline combinations vs. monotherapy in patients with advanced EGFR-mutated NSCLC was the subject of a recent “controversies in thoracic oncology” feature in the Journal of Thoracic Oncology, with Dr. Wheatley-Price and University of Ottawa colleague Sara Moore, MD, FRCPC, arguing that combining EGFR TKIs with either cytotoxic chemotherapy or antiangiogenic monoclonal antibodies targeting the vascular endothelial growth factor (VEGF) receptor has been shown consistently to improve progression-free survival (PFS) and in some cases overall survival (OS).

“There is a consistent drop-off in patients who receive second-line therapy, highlighting the importance of using combination therapy in the first-line setting to ensure patients will be exposed to multiple available therapies that may prolong survival. Chemotherapy-based combinations lead to improved response rates which may be especially helpful in patients with a significant burden of disease,” they wrote.

The authors noted that, compared with patients with wild-type EGFR, patients with EGFR-mutated NSCLC had a doubling of response rates to chemotherapy with a platinum-based doublet in the IPASS trial, suggesting that EGFR-mutated tumors may be more chemosensitive.
 

Promising trials, old drug

“Chemotherapy and EGFR TKIs may have a synergistic effect through combined reduction in vascular endothelial growth factor (VEGF)–mediated angiogenesis, and with EGFR TKIs counteracting chemotherapy-induced up-regulation of downstream EGFR signaling,” they wrote.

The authors cited two studies, one from Japan, and one from India, both of which showed significant improvements in response rates, PFS, and OS with the combination of gefitinib plus carboplatin and pemetrexed chemotherapy with pemetrexed maintenance vs. carboplatin alone,

“Now of course we don’t use gefitinib as our first-line treatment. In Canada and the United States, we use osimertinib, so certainly the chemotherapy/TKI combination, while it looks quite promising, was compared to an old control arm,” Dr. Wheatley-Price said.

He noted that the phase 3 FLAURA2 trial, currently underway, will address the question of whether adding osimertinib to a chemotherapy doublet with pemetrexed plus either carboplatin or cisplatin can improve PFS in patients with EGFR-positive locally advanced or metastatic NSCLC, compared with osimertinib alone.

The authors acknowledged that chemotherapy adds toxicities, compared with the use of TKI monotherapy, but added that, “even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

VEGF plus EGFR

Adding a VEGF-targeted monoclonal antibody or TKI to and EGFR TKI has shown consistent PFS benefits in the NEJ026, ARTEMIS, RELAY, and ACTIVE trials, Dr. Moore and Dr. Wheatley-Price noted.

“In all four trials, resistance testing at the time of progression revealed similar rates of T790M mutation in both arms, highlighting the potential role of optimizing the sequence of therapy with use of second-line osimertinib among those with a T790M resistance mutation,” they wrote.

All four trials also showed higher rates of adverse events in the combination arms, but most, except for hypertension, were low grade, and in the RELAY trial the added toxicities did not significantly affect patient quality of life, they said.
 

Monotherapy advocated

Although in agreement that the combination of gefitinib and chemotherapy has both PFS and OS benefits compared with monotherapy alone, “these combinations are not applicable to real-life practice given their use of first-generation EGFR TKIs rather than third-generation EGFR TKI osimertinib,” wrote Sophie Stock-Martineau, MD, FRCPC from Hôpital Maisonneuve-Rosemont and the University of Montreal, and Frances A. Shepherd, MD, FRCPC from the Princess Margaret Cancer Centre in Toronto, in an article touting EGFR monotherapy.

They stated that until the results of FLAURA2 are available “osimertinib alone remains the current standard first-line therapy in metastatic EGFRm+ NSCLC.”

“The addition of an antiangiogenic agent to an EGFR TKI mildly prolongs PFS; however, it does not yet translate into survival benefit. Not only does it add more toxicity to patients, but it also adds cost, which is far from negligible,” they wrote.

Dr. Stock-Martineau and Dr. Shepherd also noted that two phase 2 trials comparing afatinib with the EGFR monoclonal antibody cetuximab (Erbitux) showed no PFS or OS benefits in patients with untreated EGFR-mutated NSCLC and were terminated for lack of efficacy.

In addition, clinical trials of combinations of EGFR TKIs with immune checkpoint inhibitors ­or MET inhibitors have failed to date to demonstrate survival benefits, the authors said.

“No trials have yet revealed PFS or OS benefit with osimertinib combinations. Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system. Combinations could potentially also worsen quality of life given their heightened toxicity profiles. Therefore, single-agent EGFR TKI, such as osimertinib, remains for now the standard of care in the first-line setting for advanced EGFRm+ NSCLC,” they concluded.

No funding sources for the articles were reported. All authors declared no conflicts of interest to disclose.

Two expert analyses appearing in the same issue of the Journal of Thoracic Oncology arrive at opposite conclusions regarding the value for metastatic non–small cell lung cancer (mNSCLC) of combining first-generation endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with either chemotherapy or vascular EGF (VEGF) monoclonal antibodies. One affirms single-agent EGFR TKI treatment, such as with osimertinib, as the current standard of care for first-line advanced metastatic EGFR-positive mNSCLC, and the other affirms clear benefits for first-generation EGFR TKIs combined with either chemotherapy or VEGF monoclonal antibodies.

In the analysis supporting combination therapy for mNSCLC, Sara Moore, MD, and Paul Wheatley-Price MD, wrote that while targeted therapy with EGFR TKIs is highly effective initially, resistance inevitably develops.

Recent data, they stated, have demonstrated that combination strategies can delay development of resistance and improve outcomes for mNSCLC populations. Combining first-generation EGFR TKIs with either chemotherapy or VEGF monoclonal antibodies has led to consistent improvement in progression-free survival (PFS) and overall survival (OS) in some cases. In the NEJ009 trial, the combination of chemotherapy (carboplatin and pemetrexed, with pemetrexed maintenance) plus gefitinib versus gefitinib alone improved response rate (84% vs. 67%, P < 0.001), PFS (median, 20.9 months vs. 11.2 months; P < .001), and OS (median, 50.9 months vs. 38.8 months; P = .021). An increase in adverse events in the chemotherapy arm led to a decrease in quality of life.

Another clinical trial (by Noronha and colleagues) conducted in India of the same combination found benefit for combination therapy in response rate (75% vs. 63%), PFS (median, 16 months vs. 8 months), and OS (not reached vs. 17 months). Grade 3 or higher adverse event rates were higher with the combination (51% vs. 25%) with quality of life was not yet reported.

While both trials have been criticized owing to a lack of standard T790M resistance testing and low use of osimertinib in subsequent lines of therapy, Dr. Moore and Dr. Wheatley-Price pointed out: “Even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

The importance of using combination therapy in the first-line setting, they stated, is underscored by the consistent drop-off in patients who receive second-line combination therapy. In the phase 3 FLAURA trial of first-line osimertinib monotherapy, of the patients who discontinued osimertinib, the most common reason for not receiving subsequent therapy was death (60% went on to receive further systemic therapy). This highlights the need to use the most effective treatments up front, Dr. Moore and Dr. Wheatley-Price wrote.

The four large trials of VEGF-targeted therapy with either monoclonal antibodies or TKIs added to first-generation EGFR TKIs have consistently shown improved PFS. Increased toxicities led to discontinuation of VEGF-targeted therapy in 20%-30%.

In the RELAY trial, however, despite more toxicities, quality of life was not diminished. In general, the authors concluded that long-term detriments to quality of life have not been demonstrated. Ongoing studies of osimertinib in combination with VEGF inhibition include a phase 1/2 trial with bevacizumab in previously untreated patients showing an 80% response rate (median PFS, 18.4 months) with no unexpected toxicity.

Chemotherapy-based treatment for mNSCLC with third-generation EGFR TKIs, in appropriately selected patients, the authors concluded, “can offer an additional standard-of-care option as first-line treatment of EGFR-mutant lung cancer.”

Since the introduction of EGFR TKIs, Sophie Stock-Martineau, MD and Frances A. Shepherd, MD noted in their analysis, researchers have aimed to improve their efficacy through combining them with other agents. The authors review research on the addition of chemo- or immunotherapy and agents targeting major resistance mechanisms such as MET. Their review of the same NEJ009 trial focuses, however, on the 65.3% (EGFR TKI plus chemotherapy) versus 31.0% (gefitinib alone) grade 3 adverse event rate, and the 51% versus 25% grade 3 adverse event rate in a similar trial by Noronha and colleagues. The review by Dr. Stock-Martineau and Dr. Shepherd further found that, while adding antiangiogenic agents to an EGFR TKI “mildly” prolongs PFS, survival benefits have not been demonstrated. The added costs, not just in toxicity, were a “far from negligible” $120,000 above the cost of bevacizumab alone for 16 treatments. Data from trials of immune checkpoint inhibitors added to EGFR TKIs reveal heightened toxicities and limited efficacy. Trials of EGFR monoclonal antibodies with an EGFR TKI showed no PFS or OS benefit and were terminated early. Similarly, evidence to date shows no benefit beyond that shown for EGFR TKI monotherapy with the addition of a MET inhibitor.

“Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system,” Dr. Stock-Martineau and Dr. Shepherd concluded, further observing that combinations, given their heightened toxicity profiles, could potentially also worsen quality of life.

No conflicts of interest were reported by the authors of either study.

Two expert analyses appearing in the same issue of the Journal of Thoracic Oncology arrive at opposite conclusions regarding the value for metastatic non–small cell lung cancer (mNSCLC) of combining first-generation endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with either chemotherapy or vascular EGF (VEGF) monoclonal antibodies. One affirms single-agent EGFR TKI treatment, such as with osimertinib, as the current standard of care for first-line advanced metastatic EGFR-positive mNSCLC, and the other affirms clear benefits for first-generation EGFR TKIs combined with either chemotherapy or VEGF monoclonal antibodies.

In the analysis supporting combination therapy for mNSCLC, Sara Moore, MD, and Paul Wheatley-Price MD, wrote that while targeted therapy with EGFR TKIs is highly effective initially, resistance inevitably develops.

Recent data, they stated, have demonstrated that combination strategies can delay development of resistance and improve outcomes for mNSCLC populations. Combining first-generation EGFR TKIs with either chemotherapy or VEGF monoclonal antibodies has led to consistent improvement in progression-free survival (PFS) and overall survival (OS) in some cases. In the NEJ009 trial, the combination of chemotherapy (carboplatin and pemetrexed, with pemetrexed maintenance) plus gefitinib versus gefitinib alone improved response rate (84% vs. 67%, P < 0.001), PFS (median, 20.9 months vs. 11.2 months; P < .001), and OS (median, 50.9 months vs. 38.8 months; P = .021). An increase in adverse events in the chemotherapy arm led to a decrease in quality of life.

Another clinical trial (by Noronha and colleagues) conducted in India of the same combination found benefit for combination therapy in response rate (75% vs. 63%), PFS (median, 16 months vs. 8 months), and OS (not reached vs. 17 months). Grade 3 or higher adverse event rates were higher with the combination (51% vs. 25%) with quality of life was not yet reported.

While both trials have been criticized owing to a lack of standard T790M resistance testing and low use of osimertinib in subsequent lines of therapy, Dr. Moore and Dr. Wheatley-Price pointed out: “Even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

The importance of using combination therapy in the first-line setting, they stated, is underscored by the consistent drop-off in patients who receive second-line combination therapy. In the phase 3 FLAURA trial of first-line osimertinib monotherapy, of the patients who discontinued osimertinib, the most common reason for not receiving subsequent therapy was death (60% went on to receive further systemic therapy). This highlights the need to use the most effective treatments up front, Dr. Moore and Dr. Wheatley-Price wrote.

The four large trials of VEGF-targeted therapy with either monoclonal antibodies or TKIs added to first-generation EGFR TKIs have consistently shown improved PFS. Increased toxicities led to discontinuation of VEGF-targeted therapy in 20%-30%.

In the RELAY trial, however, despite more toxicities, quality of life was not diminished. In general, the authors concluded that long-term detriments to quality of life have not been demonstrated. Ongoing studies of osimertinib in combination with VEGF inhibition include a phase 1/2 trial with bevacizumab in previously untreated patients showing an 80% response rate (median PFS, 18.4 months) with no unexpected toxicity.

Chemotherapy-based treatment for mNSCLC with third-generation EGFR TKIs, in appropriately selected patients, the authors concluded, “can offer an additional standard-of-care option as first-line treatment of EGFR-mutant lung cancer.”

Since the introduction of EGFR TKIs, Sophie Stock-Martineau, MD and Frances A. Shepherd, MD noted in their analysis, researchers have aimed to improve their efficacy through combining them with other agents. The authors review research on the addition of chemo- or immunotherapy and agents targeting major resistance mechanisms such as MET. Their review of the same NEJ009 trial focuses, however, on the 65.3% (EGFR TKI plus chemotherapy) versus 31.0% (gefitinib alone) grade 3 adverse event rate, and the 51% versus 25% grade 3 adverse event rate in a similar trial by Noronha and colleagues. The review by Dr. Stock-Martineau and Dr. Shepherd further found that, while adding antiangiogenic agents to an EGFR TKI “mildly” prolongs PFS, survival benefits have not been demonstrated. The added costs, not just in toxicity, were a “far from negligible” $120,000 above the cost of bevacizumab alone for 16 treatments. Data from trials of immune checkpoint inhibitors added to EGFR TKIs reveal heightened toxicities and limited efficacy. Trials of EGFR monoclonal antibodies with an EGFR TKI showed no PFS or OS benefit and were terminated early. Similarly, evidence to date shows no benefit beyond that shown for EGFR TKI monotherapy with the addition of a MET inhibitor.

“Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system,” Dr. Stock-Martineau and Dr. Shepherd concluded, further observing that combinations, given their heightened toxicity profiles, could potentially also worsen quality of life.

No conflicts of interest were reported by the authors of either study.

Two expert analyses appearing in the same issue of the Journal of Thoracic Oncology arrive at opposite conclusions regarding the value for metastatic non–small cell lung cancer (mNSCLC) of combining first-generation endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with either chemotherapy or vascular EGF (VEGF) monoclonal antibodies. One affirms single-agent EGFR TKI treatment, such as with osimertinib, as the current standard of care for first-line advanced metastatic EGFR-positive mNSCLC, and the other affirms clear benefits for first-generation EGFR TKIs combined with either chemotherapy or VEGF monoclonal antibodies.

In the analysis supporting combination therapy for mNSCLC, Sara Moore, MD, and Paul Wheatley-Price MD, wrote that while targeted therapy with EGFR TKIs is highly effective initially, resistance inevitably develops.

Recent data, they stated, have demonstrated that combination strategies can delay development of resistance and improve outcomes for mNSCLC populations. Combining first-generation EGFR TKIs with either chemotherapy or VEGF monoclonal antibodies has led to consistent improvement in progression-free survival (PFS) and overall survival (OS) in some cases. In the NEJ009 trial, the combination of chemotherapy (carboplatin and pemetrexed, with pemetrexed maintenance) plus gefitinib versus gefitinib alone improved response rate (84% vs. 67%, P < 0.001), PFS (median, 20.9 months vs. 11.2 months; P < .001), and OS (median, 50.9 months vs. 38.8 months; P = .021). An increase in adverse events in the chemotherapy arm led to a decrease in quality of life.

Another clinical trial (by Noronha and colleagues) conducted in India of the same combination found benefit for combination therapy in response rate (75% vs. 63%), PFS (median, 16 months vs. 8 months), and OS (not reached vs. 17 months). Grade 3 or higher adverse event rates were higher with the combination (51% vs. 25%) with quality of life was not yet reported.

While both trials have been criticized owing to a lack of standard T790M resistance testing and low use of osimertinib in subsequent lines of therapy, Dr. Moore and Dr. Wheatley-Price pointed out: “Even with the use of first-line osimertinib monotherapy, patients may still be exposed to chemotherapy with later lines of treatment. Therefore, combination therapy does not expose patients to new toxicity, it simply changes when they will be exposed to that toxicity during their treatment course.”

The importance of using combination therapy in the first-line setting, they stated, is underscored by the consistent drop-off in patients who receive second-line combination therapy. In the phase 3 FLAURA trial of first-line osimertinib monotherapy, of the patients who discontinued osimertinib, the most common reason for not receiving subsequent therapy was death (60% went on to receive further systemic therapy). This highlights the need to use the most effective treatments up front, Dr. Moore and Dr. Wheatley-Price wrote.

The four large trials of VEGF-targeted therapy with either monoclonal antibodies or TKIs added to first-generation EGFR TKIs have consistently shown improved PFS. Increased toxicities led to discontinuation of VEGF-targeted therapy in 20%-30%.

In the RELAY trial, however, despite more toxicities, quality of life was not diminished. In general, the authors concluded that long-term detriments to quality of life have not been demonstrated. Ongoing studies of osimertinib in combination with VEGF inhibition include a phase 1/2 trial with bevacizumab in previously untreated patients showing an 80% response rate (median PFS, 18.4 months) with no unexpected toxicity.

Chemotherapy-based treatment for mNSCLC with third-generation EGFR TKIs, in appropriately selected patients, the authors concluded, “can offer an additional standard-of-care option as first-line treatment of EGFR-mutant lung cancer.”

Since the introduction of EGFR TKIs, Sophie Stock-Martineau, MD and Frances A. Shepherd, MD noted in their analysis, researchers have aimed to improve their efficacy through combining them with other agents. The authors review research on the addition of chemo- or immunotherapy and agents targeting major resistance mechanisms such as MET. Their review of the same NEJ009 trial focuses, however, on the 65.3% (EGFR TKI plus chemotherapy) versus 31.0% (gefitinib alone) grade 3 adverse event rate, and the 51% versus 25% grade 3 adverse event rate in a similar trial by Noronha and colleagues. The review by Dr. Stock-Martineau and Dr. Shepherd further found that, while adding antiangiogenic agents to an EGFR TKI “mildly” prolongs PFS, survival benefits have not been demonstrated. The added costs, not just in toxicity, were a “far from negligible” $120,000 above the cost of bevacizumab alone for 16 treatments. Data from trials of immune checkpoint inhibitors added to EGFR TKIs reveal heightened toxicities and limited efficacy. Trials of EGFR monoclonal antibodies with an EGFR TKI showed no PFS or OS benefit and were terminated early. Similarly, evidence to date shows no benefit beyond that shown for EGFR TKI monotherapy with the addition of a MET inhibitor.

“Adding virtually all agents to EGFR TKIs has been associated with more toxicity to patients and a significant financial burden to the health care system,” Dr. Stock-Martineau and Dr. Shepherd concluded, further observing that combinations, given their heightened toxicity profiles, could potentially also worsen quality of life.

No conflicts of interest were reported by the authors of either study.

Abraxane, a chemotherapy treatment for advanced pancreatic cancer, advanced non–small cell lung cancer and metastatic breast cancer, is on allocation through early March because of manufacturing delays, forcing physicians to find alternatives for a drug once lauded for being easier to tolerate.

Abraxane (Bristol-Myers Squibb) is a paclitaxel albumin-bound injectable. It is different from alternative chemotherapy treatments like Taxol (paclitaxel) because it doesn’t use the solvents that can make Taxol difficult to tolerate. It was described as a “next-generation taxane” because it didn’t rely on solvents. It was approved in 2005 for metastatic breast cancer, then in 2012 for advanced non–small cell lung cancer, in 2013 for late-stage pancreatic cancer and in 2019 for people with PD-L1–positive metastatic triple-negative breast cancer.

The shortage, which was announced on Oct. 5, 2021, by the Food and Drug Administration, has led to some difficult decisions for patients and physicians. How long the shortage will last isn’t clear.

“I printed out [an] allotment sheet 2 days ago, and all it says [for Abraxane] is allocated,” said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center, Hammond, La. “Everyone is keeping what they’ve got for their own patients, so there really isn’t anything available.”

The Pontchartrain Cancer Center sent two patients to the University of Texas MD Anderson Cancer Center, Houston, for continued treatment with Abraxane, but that option is costly and time consuming for patients. The two patients had the means to travel, but Ms. Oubre said that many others cannot afford to travel for treatment. “Everyone has patients who are living paycheck to paycheck who certainly couldn’t afford to do that. There are going to be patients across the nation that are not going to be able to have care as a result of these things.”

The supply problems are causing difficult decisions for physicians, who may have to switch a patient from an unavailable drug to an alternative that isn’t as effective, Ms. Oubre said. “I can’t imagine the stress and the sadness that the physicians have to feel when they have to go explain that to a patient. That runs counter to everything they are as physicians.”

Other strategies include chemo holidays and rounding down doses in patients with metastatic cancer, according to Camille Hill, PharmD, vice president of oncology pharmacy services, West Cancer Center, Germantown, Tenn.

Shortages and allocations are growing at an alarming rate, Ms. Oubre said. In her 15 years of working in the industry, “I don’t recall it ever being this challenging.” During a Zoom interview, she held up a lengthy list of drugs on allocation or unavailable that her pharmacy group purchasing organization sent her the previous week. “I don’t ever recall getting this kind of list. Every 3 days, I’m getting this. If it were just that one product, I can live with that. We figure it out. But it’s bigger than that.”

Worker shortages are exacerbating the issue. Ms. Oubre received a letter from a drug company describing its employee issues, which included chemists, plant workers, and loading dock staff. On top of that, delivery companies are experiencing staff shortages, which can result in more delays and complicate matters further. “It’s just compounding. These things can get really difficult very quickly. I don’t want to say we’re in crisis, and we’re not rationing care. We’re not in those buckets yet. But I would say that if these things don’t get better, it’s the first time in my work career that we are having those conversations of: ‘How we are going to plan for that it does come to that?’ ” she said.

“In general, with the pandemic, we have seen all sorts of just disruptions to the supply chain. So, I think you just do your best, you find alternatives for those patients that you can, and you come up with strategies. I don’t know that for Abraxane, or any other product, that I’d be particularly confident that we may not see another shortage,” Dr. Hill said.

Abraxane, a chemotherapy treatment for advanced pancreatic cancer, advanced non–small cell lung cancer and metastatic breast cancer, is on allocation through early March because of manufacturing delays, forcing physicians to find alternatives for a drug once lauded for being easier to tolerate.

Abraxane (Bristol-Myers Squibb) is a paclitaxel albumin-bound injectable. It is different from alternative chemotherapy treatments like Taxol (paclitaxel) because it doesn’t use the solvents that can make Taxol difficult to tolerate. It was described as a “next-generation taxane” because it didn’t rely on solvents. It was approved in 2005 for metastatic breast cancer, then in 2012 for advanced non–small cell lung cancer, in 2013 for late-stage pancreatic cancer and in 2019 for people with PD-L1–positive metastatic triple-negative breast cancer.

The shortage, which was announced on Oct. 5, 2021, by the Food and Drug Administration, has led to some difficult decisions for patients and physicians. How long the shortage will last isn’t clear.

“I printed out [an] allotment sheet 2 days ago, and all it says [for Abraxane] is allocated,” said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center, Hammond, La. “Everyone is keeping what they’ve got for their own patients, so there really isn’t anything available.”

The Pontchartrain Cancer Center sent two patients to the University of Texas MD Anderson Cancer Center, Houston, for continued treatment with Abraxane, but that option is costly and time consuming for patients. The two patients had the means to travel, but Ms. Oubre said that many others cannot afford to travel for treatment. “Everyone has patients who are living paycheck to paycheck who certainly couldn’t afford to do that. There are going to be patients across the nation that are not going to be able to have care as a result of these things.”

The supply problems are causing difficult decisions for physicians, who may have to switch a patient from an unavailable drug to an alternative that isn’t as effective, Ms. Oubre said. “I can’t imagine the stress and the sadness that the physicians have to feel when they have to go explain that to a patient. That runs counter to everything they are as physicians.”

Other strategies include chemo holidays and rounding down doses in patients with metastatic cancer, according to Camille Hill, PharmD, vice president of oncology pharmacy services, West Cancer Center, Germantown, Tenn.

Shortages and allocations are growing at an alarming rate, Ms. Oubre said. In her 15 years of working in the industry, “I don’t recall it ever being this challenging.” During a Zoom interview, she held up a lengthy list of drugs on allocation or unavailable that her pharmacy group purchasing organization sent her the previous week. “I don’t ever recall getting this kind of list. Every 3 days, I’m getting this. If it were just that one product, I can live with that. We figure it out. But it’s bigger than that.”

Worker shortages are exacerbating the issue. Ms. Oubre received a letter from a drug company describing its employee issues, which included chemists, plant workers, and loading dock staff. On top of that, delivery companies are experiencing staff shortages, which can result in more delays and complicate matters further. “It’s just compounding. These things can get really difficult very quickly. I don’t want to say we’re in crisis, and we’re not rationing care. We’re not in those buckets yet. But I would say that if these things don’t get better, it’s the first time in my work career that we are having those conversations of: ‘How we are going to plan for that it does come to that?’ ” she said.

“In general, with the pandemic, we have seen all sorts of just disruptions to the supply chain. So, I think you just do your best, you find alternatives for those patients that you can, and you come up with strategies. I don’t know that for Abraxane, or any other product, that I’d be particularly confident that we may not see another shortage,” Dr. Hill said.

Abraxane, a chemotherapy treatment for advanced pancreatic cancer, advanced non–small cell lung cancer and metastatic breast cancer, is on allocation through early March because of manufacturing delays, forcing physicians to find alternatives for a drug once lauded for being easier to tolerate.

Abraxane (Bristol-Myers Squibb) is a paclitaxel albumin-bound injectable. It is different from alternative chemotherapy treatments like Taxol (paclitaxel) because it doesn’t use the solvents that can make Taxol difficult to tolerate. It was described as a “next-generation taxane” because it didn’t rely on solvents. It was approved in 2005 for metastatic breast cancer, then in 2012 for advanced non–small cell lung cancer, in 2013 for late-stage pancreatic cancer and in 2019 for people with PD-L1–positive metastatic triple-negative breast cancer.

The shortage, which was announced on Oct. 5, 2021, by the Food and Drug Administration, has led to some difficult decisions for patients and physicians. How long the shortage will last isn’t clear.

“I printed out [an] allotment sheet 2 days ago, and all it says [for Abraxane] is allocated,” said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center, Hammond, La. “Everyone is keeping what they’ve got for their own patients, so there really isn’t anything available.”

The Pontchartrain Cancer Center sent two patients to the University of Texas MD Anderson Cancer Center, Houston, for continued treatment with Abraxane, but that option is costly and time consuming for patients. The two patients had the means to travel, but Ms. Oubre said that many others cannot afford to travel for treatment. “Everyone has patients who are living paycheck to paycheck who certainly couldn’t afford to do that. There are going to be patients across the nation that are not going to be able to have care as a result of these things.”

The supply problems are causing difficult decisions for physicians, who may have to switch a patient from an unavailable drug to an alternative that isn’t as effective, Ms. Oubre said. “I can’t imagine the stress and the sadness that the physicians have to feel when they have to go explain that to a patient. That runs counter to everything they are as physicians.”

Other strategies include chemo holidays and rounding down doses in patients with metastatic cancer, according to Camille Hill, PharmD, vice president of oncology pharmacy services, West Cancer Center, Germantown, Tenn.

Shortages and allocations are growing at an alarming rate, Ms. Oubre said. In her 15 years of working in the industry, “I don’t recall it ever being this challenging.” During a Zoom interview, she held up a lengthy list of drugs on allocation or unavailable that her pharmacy group purchasing organization sent her the previous week. “I don’t ever recall getting this kind of list. Every 3 days, I’m getting this. If it were just that one product, I can live with that. We figure it out. But it’s bigger than that.”

Worker shortages are exacerbating the issue. Ms. Oubre received a letter from a drug company describing its employee issues, which included chemists, plant workers, and loading dock staff. On top of that, delivery companies are experiencing staff shortages, which can result in more delays and complicate matters further. “It’s just compounding. These things can get really difficult very quickly. I don’t want to say we’re in crisis, and we’re not rationing care. We’re not in those buckets yet. But I would say that if these things don’t get better, it’s the first time in my work career that we are having those conversations of: ‘How we are going to plan for that it does come to that?’ ” she said.

“In general, with the pandemic, we have seen all sorts of just disruptions to the supply chain. So, I think you just do your best, you find alternatives for those patients that you can, and you come up with strategies. I don’t know that for Abraxane, or any other product, that I’d be particularly confident that we may not see another shortage,” Dr. Hill said.

Scientists at Newcastle University (England) have identified the mechanism for skin cancer growth.

Their research, published in the British Journal of Dermatology, describes how early-stage melanomas at risk of spreading secrete transforming growth factor beta₂ (TGF-beta₂), which causes the reduction, or down-regulation, of the proteins AMBRA1 and loricrin, both of which are found in the skin overlaying the tumor. TGF-beta₂ also causes the loss of claudin-1, which in turn leads to loss of skin integrity, facilitating ulceration.

Senior author Penny Lovat, PhD, professor of cellular dermatology and oncology at Newcastle University, and chief scientific officer at AMLo Biosciences, explained: “AMBRA1, loricrin, and claudin-1 are all proteins key to maintaining the integrity of the upper layer of the skin,” and that the loss of these proteins causes gaps to develop, allowing the tumor to spread and ulcerate – a process associated with high-risk tumors. Dr. Lovat likened the process to that of “mortar and bricks holding together a wall”, with the loss of these proteins being “like the mortar crumbling away in the wall.”

According to Cancer Research UK, there are over 16,000 new cases of melanoma skin cancer each year in the United Kingdom, with over 2,000 deaths annually. After being surgically removed, primary tumors are histologically staged, with even low-risk cases being followed up for a number of years, a process that can be time-consuming for patients and costly for the NHS.
 

Some reassurance for those with melanoma

The creators of the new test say that it is these low-risk patients that the test is able to identify, offering a degree of reassurance to those diagnosed with the disease, and potentially reducing the number of hospital clinic visits they require.

Dr. Lovat commented: “Our test offers a personalized prognosis as it more accurately predicts if your skin cancer is unlikely to spread.”

She added that the test will aid clinicians to identify genuinely low-risk patients diagnosed with an early-stage melanoma, reducing the number of follow-up appointments for those identified as low risk. It, therefore, offers the opportunity to save the NHS time and money.
 

Excellent news for those with skin cancer

Phil Brady, chief operating officer of the British Skin Foundation, echoed Dr. Lovat’s comments, saying: “The test can alleviate stress and anxiety for patients caused by this potentially deadly skin cancer, whilst increasing efficiency and reducing costs to the NHS.”

Nick Levell, MD, consultant dermatologist & British Skin Foundation spokesperson, who has not been involved in the research, commented how the arrival of the test was “excellent news,” adding that “people at low risk can be reassured and will not have to attend hospital so often for check-ups”.

The development of the new test AMBLor has been led by Dr. Lovat, in association with the university spin-out company AMLo Biosciences, and is accredited by the National Accreditation Body for the United Kingdom. The test involves tissue sections from the standard biopsy being sent in the post to the lab for analysis and costs £293 plus VAT. Currently available through a private referral service, the Newcastle team have applied for the test to be made available on the NHS.

A version of this article first appeared on Medscape UK.

Scientists at Newcastle University (England) have identified the mechanism for skin cancer growth.

Their research, published in the British Journal of Dermatology, describes how early-stage melanomas at risk of spreading secrete transforming growth factor beta₂ (TGF-beta₂), which causes the reduction, or down-regulation, of the proteins AMBRA1 and loricrin, both of which are found in the skin overlaying the tumor. TGF-beta₂ also causes the loss of claudin-1, which in turn leads to loss of skin integrity, facilitating ulceration.

Senior author Penny Lovat, PhD, professor of cellular dermatology and oncology at Newcastle University, and chief scientific officer at AMLo Biosciences, explained: “AMBRA1, loricrin, and claudin-1 are all proteins key to maintaining the integrity of the upper layer of the skin,” and that the loss of these proteins causes gaps to develop, allowing the tumor to spread and ulcerate – a process associated with high-risk tumors. Dr. Lovat likened the process to that of “mortar and bricks holding together a wall”, with the loss of these proteins being “like the mortar crumbling away in the wall.”

According to Cancer Research UK, there are over 16,000 new cases of melanoma skin cancer each year in the United Kingdom, with over 2,000 deaths annually. After being surgically removed, primary tumors are histologically staged, with even low-risk cases being followed up for a number of years, a process that can be time-consuming for patients and costly for the NHS.
 

Some reassurance for those with melanoma

The creators of the new test say that it is these low-risk patients that the test is able to identify, offering a degree of reassurance to those diagnosed with the disease, and potentially reducing the number of hospital clinic visits they require.

Dr. Lovat commented: “Our test offers a personalized prognosis as it more accurately predicts if your skin cancer is unlikely to spread.”

She added that the test will aid clinicians to identify genuinely low-risk patients diagnosed with an early-stage melanoma, reducing the number of follow-up appointments for those identified as low risk. It, therefore, offers the opportunity to save the NHS time and money.
 

Excellent news for those with skin cancer

Phil Brady, chief operating officer of the British Skin Foundation, echoed Dr. Lovat’s comments, saying: “The test can alleviate stress and anxiety for patients caused by this potentially deadly skin cancer, whilst increasing efficiency and reducing costs to the NHS.”

Nick Levell, MD, consultant dermatologist & British Skin Foundation spokesperson, who has not been involved in the research, commented how the arrival of the test was “excellent news,” adding that “people at low risk can be reassured and will not have to attend hospital so often for check-ups”.

The development of the new test AMBLor has been led by Dr. Lovat, in association with the university spin-out company AMLo Biosciences, and is accredited by the National Accreditation Body for the United Kingdom. The test involves tissue sections from the standard biopsy being sent in the post to the lab for analysis and costs £293 plus VAT. Currently available through a private referral service, the Newcastle team have applied for the test to be made available on the NHS.

A version of this article first appeared on Medscape UK.

Scientists at Newcastle University (England) have identified the mechanism for skin cancer growth.

Their research, published in the British Journal of Dermatology, describes how early-stage melanomas at risk of spreading secrete transforming growth factor beta₂ (TGF-beta₂), which causes the reduction, or down-regulation, of the proteins AMBRA1 and loricrin, both of which are found in the skin overlaying the tumor. TGF-beta₂ also causes the loss of claudin-1, which in turn leads to loss of skin integrity, facilitating ulceration.

Senior author Penny Lovat, PhD, professor of cellular dermatology and oncology at Newcastle University, and chief scientific officer at AMLo Biosciences, explained: “AMBRA1, loricrin, and claudin-1 are all proteins key to maintaining the integrity of the upper layer of the skin,” and that the loss of these proteins causes gaps to develop, allowing the tumor to spread and ulcerate – a process associated with high-risk tumors. Dr. Lovat likened the process to that of “mortar and bricks holding together a wall”, with the loss of these proteins being “like the mortar crumbling away in the wall.”

According to Cancer Research UK, there are over 16,000 new cases of melanoma skin cancer each year in the United Kingdom, with over 2,000 deaths annually. After being surgically removed, primary tumors are histologically staged, with even low-risk cases being followed up for a number of years, a process that can be time-consuming for patients and costly for the NHS.
 

Some reassurance for those with melanoma

The creators of the new test say that it is these low-risk patients that the test is able to identify, offering a degree of reassurance to those diagnosed with the disease, and potentially reducing the number of hospital clinic visits they require.

Dr. Lovat commented: “Our test offers a personalized prognosis as it more accurately predicts if your skin cancer is unlikely to spread.”

She added that the test will aid clinicians to identify genuinely low-risk patients diagnosed with an early-stage melanoma, reducing the number of follow-up appointments for those identified as low risk. It, therefore, offers the opportunity to save the NHS time and money.
 

Excellent news for those with skin cancer

Phil Brady, chief operating officer of the British Skin Foundation, echoed Dr. Lovat’s comments, saying: “The test can alleviate stress and anxiety for patients caused by this potentially deadly skin cancer, whilst increasing efficiency and reducing costs to the NHS.”

Nick Levell, MD, consultant dermatologist & British Skin Foundation spokesperson, who has not been involved in the research, commented how the arrival of the test was “excellent news,” adding that “people at low risk can be reassured and will not have to attend hospital so often for check-ups”.

The development of the new test AMBLor has been led by Dr. Lovat, in association with the university spin-out company AMLo Biosciences, and is accredited by the National Accreditation Body for the United Kingdom. The test involves tissue sections from the standard biopsy being sent in the post to the lab for analysis and costs £293 plus VAT. Currently available through a private referral service, the Newcastle team have applied for the test to be made available on the NHS.

A version of this article first appeared on Medscape UK.

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

The paper was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

A version of this article first appeared on Medscape.com.

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

The paper was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

A version of this article first appeared on Medscape.com.

In the United States, the risk of death from cancer overall has been continuously dropping since 1991, the American Cancer Society (ACS) noted in its latest report.

There has been an overall decline of 32% in cancer deaths as of 2019, or approximately 3.5 million cancer deaths averted, the report noted.

“This success is largely because of reductions in smoking that resulted in downstream declines in lung and other smoking-related cancers,” lead author Rebecca L. Siegel of the ACS, and colleagues, noted in the latest edition of the society’s annual report on cancer rates and trends.

The paper was published online Jan. 12 in CA: A Cancer Journal for Clinicians.

In particular, there has been a fall in both the incidence of and mortality from lung cancer, largely due to successful efforts to get people to quit smoking, but also from earlier diagnosis at a stage when the disease is far more amenable to treatment, noted the authors.

For example, the incidence of lung cancer declined by almost 3% per year in men between the years 2009 and 2018 and by 1% a year in women. Currently, the historically large gender gap in lung cancer incidence is disappearing such that in 2018, lung cancer rates were 24% higher in men than they were in women, and rates in women were actually higher in some younger age groups than they were in men.

Moreover, 28% of lung cancers detected in 2018 were found at a localized stage of disease compared with 17% in 2004.

Patients diagnosed with lung cancer are also living longer, with almost one-third of lung cancer patients still alive 3 years after their diagnosis compared with 21% a decade ago.

However, lung cancer is still the biggest contributor to cancer-related mortality overall, at a death toll of 350 per day – more than breast, prostate, and pancreatic cancer combined, the authors wrote.

This is 2.5 times higher than the death rate from colorectal cancer (CRC), the second leading cause of cancer death in the United States, they added.

Nevertheless, the decrease in lung cancer mortality accelerated from 3.1% per year between 2010 and 2014 to 5.4% per year during 2015 to 2019 in men and from 1.8% to 4.3% in women. “Overall, the lung cancer death rate has dropped by 56% from 1990 to 2019 in men and by 32% from 2002 to 2019 in women,” Ms. Siegel and colleagues emphasized.

Overall, the ACS projects there will be over 1.9 million new cancer cases and over 600,000 cancer deaths across the United States in 2022.


 

Patterns are changing

With prostate cancer now accounting for some 27% of all cancer diagnoses in men, recent trends in the incidence of prostate cancer are somewhat worrisome, the authors wrote. While the incidence for local-stage disease remained stable from 2014 through to 2018, the incidence of advanced-stage disease has increased by 6% a year since 2011. “Consequently, the proportion of distant-stage diagnoses has more than doubled,” the authors noted, “from a low of 3.9% in 2007 to 8.2% in 2018.”

The incidence of breast cancer among women has been slowly increasing by 0.5% per year since about the mid-2000s. This increase is due at least in part to declines in fertility and increases in body weight among women, the authors suggested. Declines in breast cancer mortality have slowed in recent years, dropping from 1% per year from 2013 to 2019 from 2%-3% per year seen during the 1990s and the early 2000s.

As for CRC, incidence patterns are similar by sex but differ by age. For example, incidence rates of CRC declined by about 2% per year between 2014 and 2018 in individuals 50 years and older, but they increased by 1.5% per year in adults under the age of 50. Overall, however, mortality from CRC decreased by about 2% per year between 2010 and 2019, although this trend again masks increasing mortality from CRC among younger adults, where death rates rose by 1.2% per year from 2005 through 2019 in patients under the age of 50.

The third leading cause of death in men and women combined is pancreatic cancer. Here again, mortality rates slowly increased in men between 2000 and 2013 but have remained relatively stable in women.

Between 2010 and 2019, cancers of the tongue, tonsils, and oropharynx caused by human papilloma virus (HPV) increased by about 2% per year in men and by 1% per year in women.

Death from cervical cancer – despite its being one of the most preventable cancers overall – is still the second leading cause of cancer death in women between 20 and 39 years of age. “Most of these women have never been screened so this is low-hanging fruit easily addressed by increasing access to screening and [HPV] vaccination among underserved women,” Ms. Siegel said in a statement.

On the other hand, mortality from liver cancer – having increased rapidly over the past number of decades – appears to have stabilized in more recent years.
 

Survival at 5 years

For all cancers combined, survival at 5 years between the mid-1970s and 2011 through 2017 increased from 50% to 68% for White patients and by 39% to 63% for Black patients. “For all stages combined, survival is highest for prostate cancer (98%), melanoma of the skin (93%) and female breast cancer (90%),” the authors pointed out.

In contrast, survival at 5 years is lowest, at 11% for pancreatic cancer, 20% for cancers of the liver and esophagus, and 22% for lung cancer.

Indeed, for most of the common cancers, cancer survival has improved since the mid-1970s with the exception or uterine and cervical cancer, the latter because there have been few advancements in treatment.

Even among the more rare blood and lymphoid malignancies, improvements in treatment strategies, including the use of targeted therapies, have resulted in major survival gains from around 20% in the mid-1970s for chronic myeloid leukemia (CML) patients to over 70% for CML patients diagnosed between 2011 and 2017.

Similarly, the discovery and use of immunotherapy has doubled 5-year survival rates to 30% for patients with metastatic melanoma from 15% in 2004. On the other hand, racial disparities in survival odds continue to persist. For every cancer type except for cancer of the pancreas and kidney, survival rates were lower for Black patients than for White patients, the researchers pointed out.

“Black individuals also have lower stage-specific survival for most cancer types,” the report authors noted. Indeed, after adjustment for sex, age, and stage at diagnosis, the risk of death is 33% higher in Black patients than White patients and 51% higher in American Indian/Alaska Natives compared to White patients.

That said, the overall incidence of cancer is still highest among White individuals, in part because of high rates of breast cancer in White women, which may in part reflect overdiagnosis of breast cancer in this patient population, as the authors suggested.

“However, Black women have the highest cancer mortality rates – 12% higher than White women,” they observed. Even more striking, Black women have a 4% lower incidence of breast cancer than White women but a 41% higher mortality risk from it.

As for pediatric and adolescent cancers, incidence rates may be increasing slightly among both age groups, but dramatic reductions in death by 71% among children and by 61% among adolescents from the mid-70s until now continue as a singular success story in the treatment of cancer overall.

All the authors are employed by the ACS.

A version of this article first appeared on Medscape.com.

Nearly 1 in 5 women who receive the recommended 10 biennial screening rounds for breast cancer in Norway will get a false positive result, and 1 in 20 women will receive a false positive result that leads to an invasive procedure, a new analysis shows.

While the risk may seem high, it is actually much lower than what researchers have reported in the U.S., the study authors note in their paper, published online Dec. 21 in Cancer.

“I am proud about the low rate of recalls we have in Norway and Europe – and hope we can keep it that low for the future,” said senior author Solveig Hofvind, PhD, head of BreastScreen Norway, a nationwide screening program that invites women aged 50 to 69 to mammographic screening every other year.

“The double reading in Europe is probably the main reason for the lower rate in Europe compared to the U.S., where single reading is used,” she said in an interview.

Until now, Dr. Hofvind and her colleagues say, no studies have been performed using exclusively empirical data to describe the cumulative risk of experiencing a false positive screening result in Europe because of the need for long-term follow-up and complete data registration.

For their study, the researchers turned to the Cancer Registry of Norway, which administers BreastScreen Norway. They focused on data from 1995 to 2019 on women aged 50 to 69 years who had attended one or more screening rounds and could potentially attend all 10 screening examinations over the 20-year period.

Women were excluded if they were diagnosed with breast cancer before attending screening, participated in interventional research, self-referred for screening, were recalled due to self-reported symptoms or technically inadequate mammograms, or declined follow-up after a positive screen.

Among more than 421,000 women who underwent nearly 1.9 million screening examinations, 11.3% experienced at least one false positive result and 3.3% experienced at least one false positive involving an invasive procedure, such as fine-needle aspiration cytology, core-needle biopsy, or open biopsy.

The cumulative risk of experiencing a first false positive screen was 18.0% and that of experiencing a false positive that involved an invasive procedure was 5.01%. Adjusting for irregular attendance, age at screening, or the number of screens attended had little effect on the estimates.

The results closely match earlier findings from Norway that have been based on assumptions rather than exclusively empirical data. However, these findings differ from results reported in U.S. studies, which have relied largely on data from the Breast Cancer Surveillance Consortium, the researchers say.

“The latter have indicated that, for women who initiate biennial screening at the age of 50 years, the cumulative risk after 10 years is 42% for experiencing at least one false-positive screening result and 6.4% for experiencing at least one false-positive screening result involving an invasive procedure,” Dr. Hofvind and her colleagues write.

Several principal investigators with the Breast Cancer Surveillance Consortium did not respond or were unavailable for comment when contacted by this news organization.

However, the study authors highlighted several factors that could help explain the discrepancy between the U.S. and European results.

In addition to double mammogram reading, “European guidelines recommend that breast radiologists read 3,500 to 11,000 mammograms annually, whereas 960 every 2 years are required by the U.S. Mammography Quality Standards Act,” the researchers note. They also point out that previous screening mammograms are readily available in Norway, whereas this is not always the case in the U.S.

“False-positive screening results are a part of the screening for breast cancer – and the women need to be informed about the risk,” Dr. Hofvind concluded. “The screening programs should aim to keep the rate as low as possible for the women [given] the costs.”

The study was supported by the Dam Foundation via the Norwegian Breast Cancer Society.

A version of this article first appeared on Medscape.com.

Nearly 1 in 5 women who receive the recommended 10 biennial screening rounds for breast cancer in Norway will get a false positive result, and 1 in 20 women will receive a false positive result that leads to an invasive procedure, a new analysis shows.

While the risk may seem high, it is actually much lower than what researchers have reported in the U.S., the study authors note in their paper, published online Dec. 21 in Cancer.

“I am proud about the low rate of recalls we have in Norway and Europe – and hope we can keep it that low for the future,” said senior author Solveig Hofvind, PhD, head of BreastScreen Norway, a nationwide screening program that invites women aged 50 to 69 to mammographic screening every other year.

“The double reading in Europe is probably the main reason for the lower rate in Europe compared to the U.S., where single reading is used,” she said in an interview.

Until now, Dr. Hofvind and her colleagues say, no studies have been performed using exclusively empirical data to describe the cumulative risk of experiencing a false positive screening result in Europe because of the need for long-term follow-up and complete data registration.

For their study, the researchers turned to the Cancer Registry of Norway, which administers BreastScreen Norway. They focused on data from 1995 to 2019 on women aged 50 to 69 years who had attended one or more screening rounds and could potentially attend all 10 screening examinations over the 20-year period.

Women were excluded if they were diagnosed with breast cancer before attending screening, participated in interventional research, self-referred for screening, were recalled due to self-reported symptoms or technically inadequate mammograms, or declined follow-up after a positive screen.

Among more than 421,000 women who underwent nearly 1.9 million screening examinations, 11.3% experienced at least one false positive result and 3.3% experienced at least one false positive involving an invasive procedure, such as fine-needle aspiration cytology, core-needle biopsy, or open biopsy.

The cumulative risk of experiencing a first false positive screen was 18.0% and that of experiencing a false positive that involved an invasive procedure was 5.01%. Adjusting for irregular attendance, age at screening, or the number of screens attended had little effect on the estimates.

The results closely match earlier findings from Norway that have been based on assumptions rather than exclusively empirical data. However, these findings differ from results reported in U.S. studies, which have relied largely on data from the Breast Cancer Surveillance Consortium, the researchers say.

“The latter have indicated that, for women who initiate biennial screening at the age of 50 years, the cumulative risk after 10 years is 42% for experiencing at least one false-positive screening result and 6.4% for experiencing at least one false-positive screening result involving an invasive procedure,” Dr. Hofvind and her colleagues write.

Several principal investigators with the Breast Cancer Surveillance Consortium did not respond or were unavailable for comment when contacted by this news organization.

However, the study authors highlighted several factors that could help explain the discrepancy between the U.S. and European results.

In addition to double mammogram reading, “European guidelines recommend that breast radiologists read 3,500 to 11,000 mammograms annually, whereas 960 every 2 years are required by the U.S. Mammography Quality Standards Act,” the researchers note. They also point out that previous screening mammograms are readily available in Norway, whereas this is not always the case in the U.S.

“False-positive screening results are a part of the screening for breast cancer – and the women need to be informed about the risk,” Dr. Hofvind concluded. “The screening programs should aim to keep the rate as low as possible for the women [given] the costs.”

The study was supported by the Dam Foundation via the Norwegian Breast Cancer Society.

A version of this article first appeared on Medscape.com.

Nearly 1 in 5 women who receive the recommended 10 biennial screening rounds for breast cancer in Norway will get a false positive result, and 1 in 20 women will receive a false positive result that leads to an invasive procedure, a new analysis shows.

While the risk may seem high, it is actually much lower than what researchers have reported in the U.S., the study authors note in their paper, published online Dec. 21 in Cancer.

“I am proud about the low rate of recalls we have in Norway and Europe – and hope we can keep it that low for the future,” said senior author Solveig Hofvind, PhD, head of BreastScreen Norway, a nationwide screening program that invites women aged 50 to 69 to mammographic screening every other year.

“The double reading in Europe is probably the main reason for the lower rate in Europe compared to the U.S., where single reading is used,” she said in an interview.

Until now, Dr. Hofvind and her colleagues say, no studies have been performed using exclusively empirical data to describe the cumulative risk of experiencing a false positive screening result in Europe because of the need for long-term follow-up and complete data registration.

For their study, the researchers turned to the Cancer Registry of Norway, which administers BreastScreen Norway. They focused on data from 1995 to 2019 on women aged 50 to 69 years who had attended one or more screening rounds and could potentially attend all 10 screening examinations over the 20-year period.

Women were excluded if they were diagnosed with breast cancer before attending screening, participated in interventional research, self-referred for screening, were recalled due to self-reported symptoms or technically inadequate mammograms, or declined follow-up after a positive screen.

Among more than 421,000 women who underwent nearly 1.9 million screening examinations, 11.3% experienced at least one false positive result and 3.3% experienced at least one false positive involving an invasive procedure, such as fine-needle aspiration cytology, core-needle biopsy, or open biopsy.

The cumulative risk of experiencing a first false positive screen was 18.0% and that of experiencing a false positive that involved an invasive procedure was 5.01%. Adjusting for irregular attendance, age at screening, or the number of screens attended had little effect on the estimates.

The results closely match earlier findings from Norway that have been based on assumptions rather than exclusively empirical data. However, these findings differ from results reported in U.S. studies, which have relied largely on data from the Breast Cancer Surveillance Consortium, the researchers say.

“The latter have indicated that, for women who initiate biennial screening at the age of 50 years, the cumulative risk after 10 years is 42% for experiencing at least one false-positive screening result and 6.4% for experiencing at least one false-positive screening result involving an invasive procedure,” Dr. Hofvind and her colleagues write.

Several principal investigators with the Breast Cancer Surveillance Consortium did not respond or were unavailable for comment when contacted by this news organization.

However, the study authors highlighted several factors that could help explain the discrepancy between the U.S. and European results.

In addition to double mammogram reading, “European guidelines recommend that breast radiologists read 3,500 to 11,000 mammograms annually, whereas 960 every 2 years are required by the U.S. Mammography Quality Standards Act,” the researchers note. They also point out that previous screening mammograms are readily available in Norway, whereas this is not always the case in the U.S.

“False-positive screening results are a part of the screening for breast cancer – and the women need to be informed about the risk,” Dr. Hofvind concluded. “The screening programs should aim to keep the rate as low as possible for the women [given] the costs.”

The study was supported by the Dam Foundation via the Norwegian Breast Cancer Society.

A version of this article first appeared on Medscape.com.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

To reduce risks of lung cancer mortality, interventions designed to improve high-risk groups’ uptake of low-dose CT (LDCT) lung cancer screening should focus on perceptions of lung cancer controllability, survival, and perceived effectiveness of changes in behavior, according to analysis of data from the SUMMIT study recently published in the Journal of Thoracic Oncology. Such an approach may be more effective than trying to change risk perceptions.

While 1-year survival among patients diagnosed with early-stage lung cancer is 88%, it is only 19% for those diagnosed with advanced disease. But only 27% of patients are diagnosed with early-stage disease. Screening high-risk asymptomatic adults using LDCT detects early-stage disease and significantly reduces lung cancer mortality, according to Samantha L. Quaife, PhD, of the Wolfson Institute of Population Health at Queen Mary University of London, and associates.

The effectiveness and equity of LDCT lung cancer screening as a population-level early detection strategy is compromised by low uptake among high-risk groups, the authors wrote.

In the United States, only 2% of eligible smokers have been screened since screening was first recommended in 2013. To provide a scientific evidence base for intervention, an understanding of factors making high-risk groups less likely to participate in LDCT screening is critical, Dr. Quaife and colleagues wrote.

Their longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake included 44,000 ever-smokers (aged 55-77 years) who were invited to mail a self-regulatory questionnaire for lung cancer screening. Eligibility for LDCT lung cancer screening and inclusion in the SUMMIT study were further determined through telephone and in-person Lung Health Check (LHC) appointments. The primary outcome was uptake of the invitation to book an LHC appointment by telephone.

Of those invited, 7,966 (18.1%) returned the questionnaire with 7,730 (45% female; mean age, about 64 years) linked to screening uptake data. About 30% reported being current smokers with high tobacco dependence (60.3% smoking within 30 minutes of waking). The analysis from Dr. Quaife and colleagues looked at psychological correlates of lung cancer screening uptake using a psychometrically validated self-regulatory questionnaire for lung cancer screening (SRQ-LCS) to measure psychological constructs hypothesized to be associated with uptake which included consequences, emotional representation, coherence (lung cancer knowledge), treatment control, personal control, risk perception, perceived stigma, response efficacy of smoking cessation, early diagnosis behavioral response, survival from lung cancer, and treatment intention.

Among those who perceived early diagnosis to be more beneficial as a behavioral response, the positive association with uptake was strongest (adjusted odds ratio, 1.37; 95% confidence interval, 1.33-1.41). Those who perceived greater personal control (aOR, 1.09; 95% CI, 1.05-1.11) or believed their risk of lung cancer was high (aOR, 1.08; 95% CI, 1.05-1.10) were also more likely to respond. Other uptake increases were found for those who perceived smoking cessation as an effective means of reducing lung cancer risk or thought the chances of surviving early-stage lung cancer were good or fair (P < .01), and for those who perceived lung cancer as stigmatized (aOR, 1.26; 95% CI, 1.14-1.40). Most of these constructs were also perceived more negatively by current than former smokers.

Income, employment, education, social class, and housing conditions were significantly associated with many of the constructs. Greater affluence correlated with perceived personal control and benefit from early diagnosis, but more negative perceptions of the consequences of lung cancer. Also, those from more affluent areas were more likely to perceive lung cancer to be stigmatized and perceive smoking cessation to be less effective in reducing risk. Current daily smokers were less willing to be treated for early-stage disease, more pessimistic about survival, but had the highest-risk perception scores, at odds with their lower participation in lung screening trials. This contradiction, Dr. Quaife and colleagues suggested, may be explained by current smokers also holding more negative perceptions associated with lower uptake, including negative perceptions of lung cancer controllability, early diagnosis and survival, lower willingness to be treated, and belief that smoking cessation is less effective in reducing risk. All of these undermine positive responses to their high perceived risk.

“These findings pinpoint specific psychological targets for intervention,” the authors wrote. Experimental studies investigating the methods and mechanisms through which these perceptions could be changed are needed.

The study was funded by Cancer Research UK Population Research Fellowship (C50664/A24460) awarded to Dr. Quaife. The study investigators declared no support from financial organizations that might have an interest in the submitted work in the previous 3 years.

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.

A new analysis of cardiovascular adverse drug reactions for non–small cell lung cancer (NCSLC)–targeted therapies finds that ALK and ROS1 inhibitors are associated with higher odds of conduction disease and QT prolongation than BRAF and EGFR inhibitors.

The findings are especially important because cardiovascular disease is known to be associated with NSCLC. Even before the start of therapy, 14%-22% of patients with stage I-IV NSCLC have heart failure and 26%-31% of patients have arrhythmias. No other study to date has described cardiovascular effects to this extent as a result of treatment.

The findings were published in the Journal of Thoracic Oncology.

Led by Joel W. Neal, MD, PhD, a medical oncologist at Stanford (Calif.) Health Care, researchers evaluated the association between NSCLC-targeted agents with arrhythmia and heart failure. Their findings are based on analysis of data from the World Health Organization pharmacovigilance database VigiBase. They found that of 98,765 adverse reactions, 61,383 occurred in patients treated with EGFR inhibitors, 15,540 were associated with ALK inhibitors, and 21,842 were associated with BRAF and MEK inhibitors. Arrhythmias occurred in 1,783 patients and 1,146 patients had heart failure.
 

The specifics

Strong associations with conduction disease and QT prolongation were found for ALK and ROS1 inhibitors, especially crizotinib. Of QT prolongation cases, 38.5% of patients on ceritinib and 18.4% of patients on crizotinib also had conduction disease and 7.9% of alectinib-associated conduction disease cases also had prolongation.

BRAF and MEK inhibitors had stronger associations with heart failure, while osimertinib, a third-generation EGFR tyrosine kinase inhibitor, was strongly associated with QT prolongation, supraventricular tachycardia, and heart failure.

ALK inhibitors were found to be 13 times more likely to lead to conduction disease and five times more likely to lead to lead to long QT syndrome as compared to all NSCLC-targeted therapies together. ALK inhibitor crizotinib had significantly higher odds of conduction disease, compared with all other targeted therapies, but of all ALK inhibitors, ceritinib and lorlatinib had the lowest odds of conduction disease. Crizotinib was 1.9 times more likely to lead to QT prolongation than other ALK inhibitors.

The EGFR inhibitor osimertinib was associated with 49 times more like to lead to long QT syndrome than other EGFR inhibitors and 6 times more likely as compared with all other targeted therapies. The EGFR inhibitor gefitinib was twice as likely than other EGFR inhibitors to lead to conduction disease. The third-generation EGFR inhibitor osimertinib had approximately two times higher odds of supraventricular tachycardia than other EGFR inhibitors.

Osimertinib was associated with 6.8 times higher chances of heart failure, compared with other EGFR inhibitors, and 3.6 times more than other targeted therapies. Dabrafenib and trametinib were associated with two to three times higher odds of heart failure as compared with other targeted therapies.

“There is a need for an understanding of the mechanisms underlying these toxicities and for additional studies to establish standardized guidelines for monitoring, particularly for osimertinib, crizotinib, and alectinib,” the authors wrote

The authors disclosed a number of paid advisory roles with various pharmaceutical companies.

Patients diagnosed with breast cancer during incarceration are unlikely to receive neoadjuvant therapy and have an increase time to surgery if they have the procedure upfront compared to other patients, suggests a new study.

The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).

Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.

They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.

“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.

Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”

Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”

The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”

Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.

Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.

The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).

“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.

No funding or relevant financial relationships were declared for this featured study.

Patients diagnosed with breast cancer during incarceration are unlikely to receive neoadjuvant therapy and have an increase time to surgery if they have the procedure upfront compared to other patients, suggests a new study.

The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).

Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.

They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.

“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.

Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”

Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”

The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”

Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.

Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.

The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).

“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.

No funding or relevant financial relationships were declared for this featured study.

Patients diagnosed with breast cancer during incarceration are unlikely to receive neoadjuvant therapy and have an increase time to surgery if they have the procedure upfront compared to other patients, suggests a new study.

The study was presented at the 2021 San Antonio Breast Cancer Symposium on Dec. 10 (Abstract P5-14-10).

Examining the records of more than 4,300 patients with breast cancer who were treated between 2014 and 2020 in North Carolina, researchers identified 34 who were either incarcerated at the time of diagnosis or who were diagnosed before they were imprisoned.

They found that neoadjuvant therapy was not given to incarcerated breast cancer patients as compared to 8% of women who were never incarcerated and 20% of women incarcerated later. Incarcerated patients treated with surgery upfront had to wait on average more than 3 weeks longer than other patients for their procedure. Their findings were followed by a recently published study in JAMA Network Open indicating that young people with a history of incarceration were significantly more likely to experience early mortality and that mortality was higher among Black prisoners.

“These findings are concerning for missed treatment opportunities within the carceral system,” wrote researchers who were led by Oluwadamilola “Lola” Fayanju, MD, MPHS, FACS, chief of breast surgery for the University of Pennsylvania Health System, Philadelphia.

Dr. Fayanju told this news organization that she was “not surprised by the finding that there was no neoadjuvant chemotherapy given to patients at all. Even in the practice of care outside of the carceral system it is striking how much variation there is in regards to treatment sequence if it is not approached in an evidence-based way. Many of the social ills that contribute to incarceration also contribute to this variation in care, and it’s not surprising that in women who are experiencing incarceration, there is geometric escalation of disparities with regards to their opportunities for treatment.”

Erica L. Mayer, MD, MPH, a medical oncologist and clinical investigator in the Breast Oncology Center at the Dana-Faber Cancer Institute, Boston, said “this is really interesting and important work showing some worrisome trends. On the one hand, this is a very small experience and such a small sample size is always vulnerable to bias or skew from factors that become more important. However, this is not the first observation that there are disparities of care in incarcerated populations,”said Dr. Mayer, who was not involved in the study. “This is a topic that has been studied in diseases outside of oncology, such as heart disease and diabetes. There is a theme that patients who are incarcerated have a disparity and inequity of care compared to those who are not.”

The current findings “fit in with general themes,” she said. As rates of cancer are expected to grow in the coming years, “understanding how to provide the best possible care in those settings is very important. This is early data but it’s an important signal and is suggesting to us that a greater understanding of health care access for incarcerated individuals is a very important area of study, and hopefully an area for which one could provide interventions that might help to reduce these disparities.”

Dr. Fayanju and associates. set out to determine the disease and treatment characteristics of individuals with breast cancer and a history of incarceration. They focused on women who had a breast cancer diagnosis at the University of North Carolina Hospitals between April 2014 and December 2020. They gathered data on patient demographics, incarceration status, disease characteristics, treatment types, and dates of receipt of treatment, but there were few data available. “It is really striking how little data there is available. This is a very small study and is the best we could glean from a large state-wide dataset,” she said.

Of 4,332 breast cancer cases, 34 (0.8%) were diagnosed while incarcerated (70.6%) or before incarceration (29.4%). Those who were diagnosed during incarceration were significantly more likely to be single (P < .001), use illicit drugs at the time of diagnosis (P = .01), and have a family history of breast cancer (P = .03) as compared with patients who were never incarcerated and those who were diagnosed before incarceration.

The results also showed that patients diagnosed with breast cancer during incarceration were significantly less likely to receive neoadjuvant therapy at 0% versus 8.2% for those who were never incarcerated, and 20% for those who were diagnosed before incarceration (P = .01 for trend).

“Further research is needed to understand the full scope of cancer inequities and identify factors that contribute to them among patients who experience incarceration,” Dr. Fayanju said.

No funding or relevant financial relationships were declared for this featured study.