M. Alexander Otto, PA, MMS

The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).

The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.

MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.

“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Dostarlimab was already approved in the United States as monotherapy for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.

Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.

Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.

The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.

Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.

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

The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).

The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.

MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.

“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Dostarlimab was already approved in the United States as monotherapy for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.

Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.

Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.

The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.

Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.

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

The U.S. Food and Drug Administration has approved dostarlimab-gxly (Jemperli, GlaxoSmithKline) with carboplatin and paclitaxel, followed by single-agent dostarlimab, for primary advanced or recurrent endometrial cancer that is mismatch repair–deficient (dMMR), as determined by an FDA-approved test or microsatellite instability–high (MSI-H).

The approval was based on GSK’s RUBY trial. Across 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer, progression-free survival was 30.3 months in women randomly assigned to dostarlimab on a background of carboplatin and paclitaxel, followed by dostarlimab monotherapy, vs. 7.7 months among women randomly assigned to placebo (hazard ratio, 0.29; P < .0001), according to the FDA’s press release.

MMR/MSI tumor status was determined by local testing or by the Ventana MMR RxDx Panel when local testing was unavailable.

“Until now, chemotherapy alone has been the standard of care with many patients experiencing disease progression,” GSK executive Hesham Abdullah said in the company’s press release. The trial results “and today’s approval underscore our belief in the potential for Jemperli to transform cancer treatment as a backbone immuno-oncology therapy.”

Dostarlimab was already approved in the United States as monotherapy for adults with dMMR recurrent or advanced endometrial cancer that has progressed on or following a platinum-containing chemotherapy and is not a candidate for curative surgery or radiation. The latest approval means that the agent “is now indicated earlier in treatment in combination with chemotherapy,” GSK said.

Dostarlimab also carries an indication for dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment when there are no satisfactory alternative treatment options.

Immune-mediated adverse reactions with dostarlimab include pneumonitis, colitis, hepatitis, endocrinopathies such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥ 20%) with carboplatin and paclitaxel in the Ruby trial were rash, diarrhea, hypothyroidism, and hypertension.

The recommended dostarlimab dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.

Drugs.com lists dostarlimab’s price at $11,712.66 for 500 mg/10 mL intravenous solution.

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

TOPLINE

The use of magnetic resonance–guided daily adaptive stereotactic body radiotherapy for patients with prostate cancer reduces the risk of acute urinary side effects of grade 2 or higher by 44% and the risk of acute bowel side effects of grade 2 or higher by 60%, compared with standard CT-guided SBRT (CT‐SBRT).

METHODOLOGY

• With the use of magnetic resonance–guided daily adaptive SBRT, clinicians can customize radiation dosing to accommodate changes in prostate anatomy during treatment, which may also make SBRT safer and less toxic for patients.
• To determine whether this approach does reduce patient side effects, investigators ran a meta-analysis that included 29 studies with 2547 patients comparing the incidence of short-term, physician-assessed bowel and genitourinary side effects between the MRI-guided approach and standard CT-SBRT.
• The investigators reported no statistically significant differences in age, prescribed radiation doses, planning target volumes, or International Prostatism Symptom Scores between the two groups; the use of rectal spacers and the number of patients who received pelvic lymph node radiation were low in both.
• The average window for collecting acute toxicity data was 70 days in the MRI-guided investigations and 94 days in CT-SBRT investigations.

TAKEAWAY

• The pooled estimate for acute grade 2 or higher genitourinary toxicity was 16% with MRI-guided SBRT versus 28% with CT-SBRT (odds ratio, 0.56; P = .04).
• The pooled estimate for grade 2 or higher gastrointestinal toxicity was 4% with the MRI approach versus 9% with CT-SBRT (OR, 0.40; P = .04).
• There were no differences in grade 3 or higher events, which were rare, between the groups.
• There was also no difference in toxicity among CT‐SBRT studies that used fiducial markers and those that did not.

IN PRACTICE

“These findings suggest that the technical advantages in precision of radiotherapy delivery afforded by [MRI-guided] SBRT translate to measurable clinical benefit,” the authors concluded. Potential reasons for the reduced risk of acute toxicity with the MRI-guided approach include “daily online adaptive planning, MRI‐based contouring that results in smaller treatment volumes, and MRI tracking, all of which may facilitate the precision and accuracy of treatment delivery.”

SOURCE

The study was led by Jonathan Leeman, MD, of the Dana-Farber Cancer Institute, Boston, and was published July 24 in Cancer.

LIMITATIONS

• The analysis did not account for differences in dosimetry, radiation planning, and toxicity management and assessment between the studies.
• Late toxicity and cancer control rates were not tracked and may have differed between the two approaches.

DISCLOSURES

• No external funding was reported.
• The investigators reported grants and consulting, personal, and other payments from Novartis, AstraZeneca, Janssen, and other companies.

A version of this article appeared on Medscape.com.

TOPLINE

The use of magnetic resonance–guided daily adaptive stereotactic body radiotherapy for patients with prostate cancer reduces the risk of acute urinary side effects of grade 2 or higher by 44% and the risk of acute bowel side effects of grade 2 or higher by 60%, compared with standard CT-guided SBRT (CT‐SBRT).

METHODOLOGY

• With the use of magnetic resonance–guided daily adaptive SBRT, clinicians can customize radiation dosing to accommodate changes in prostate anatomy during treatment, which may also make SBRT safer and less toxic for patients.
• To determine whether this approach does reduce patient side effects, investigators ran a meta-analysis that included 29 studies with 2547 patients comparing the incidence of short-term, physician-assessed bowel and genitourinary side effects between the MRI-guided approach and standard CT-SBRT.
• The investigators reported no statistically significant differences in age, prescribed radiation doses, planning target volumes, or International Prostatism Symptom Scores between the two groups; the use of rectal spacers and the number of patients who received pelvic lymph node radiation were low in both.
• The average window for collecting acute toxicity data was 70 days in the MRI-guided investigations and 94 days in CT-SBRT investigations.

TAKEAWAY

• The pooled estimate for acute grade 2 or higher genitourinary toxicity was 16% with MRI-guided SBRT versus 28% with CT-SBRT (odds ratio, 0.56; P = .04).
• The pooled estimate for grade 2 or higher gastrointestinal toxicity was 4% with the MRI approach versus 9% with CT-SBRT (OR, 0.40; P = .04).
• There were no differences in grade 3 or higher events, which were rare, between the groups.
• There was also no difference in toxicity among CT‐SBRT studies that used fiducial markers and those that did not.

IN PRACTICE

“These findings suggest that the technical advantages in precision of radiotherapy delivery afforded by [MRI-guided] SBRT translate to measurable clinical benefit,” the authors concluded. Potential reasons for the reduced risk of acute toxicity with the MRI-guided approach include “daily online adaptive planning, MRI‐based contouring that results in smaller treatment volumes, and MRI tracking, all of which may facilitate the precision and accuracy of treatment delivery.”

SOURCE

The study was led by Jonathan Leeman, MD, of the Dana-Farber Cancer Institute, Boston, and was published July 24 in Cancer.

LIMITATIONS

• The analysis did not account for differences in dosimetry, radiation planning, and toxicity management and assessment between the studies.
• Late toxicity and cancer control rates were not tracked and may have differed between the two approaches.

DISCLOSURES

• No external funding was reported.
• The investigators reported grants and consulting, personal, and other payments from Novartis, AstraZeneca, Janssen, and other companies.

A version of this article appeared on Medscape.com.

TOPLINE

The use of magnetic resonance–guided daily adaptive stereotactic body radiotherapy for patients with prostate cancer reduces the risk of acute urinary side effects of grade 2 or higher by 44% and the risk of acute bowel side effects of grade 2 or higher by 60%, compared with standard CT-guided SBRT (CT‐SBRT).

METHODOLOGY

• With the use of magnetic resonance–guided daily adaptive SBRT, clinicians can customize radiation dosing to accommodate changes in prostate anatomy during treatment, which may also make SBRT safer and less toxic for patients.
• To determine whether this approach does reduce patient side effects, investigators ran a meta-analysis that included 29 studies with 2547 patients comparing the incidence of short-term, physician-assessed bowel and genitourinary side effects between the MRI-guided approach and standard CT-SBRT.
• The investigators reported no statistically significant differences in age, prescribed radiation doses, planning target volumes, or International Prostatism Symptom Scores between the two groups; the use of rectal spacers and the number of patients who received pelvic lymph node radiation were low in both.
• The average window for collecting acute toxicity data was 70 days in the MRI-guided investigations and 94 days in CT-SBRT investigations.

TAKEAWAY

• The pooled estimate for acute grade 2 or higher genitourinary toxicity was 16% with MRI-guided SBRT versus 28% with CT-SBRT (odds ratio, 0.56; P = .04).
• The pooled estimate for grade 2 or higher gastrointestinal toxicity was 4% with the MRI approach versus 9% with CT-SBRT (OR, 0.40; P = .04).
• There were no differences in grade 3 or higher events, which were rare, between the groups.
• There was also no difference in toxicity among CT‐SBRT studies that used fiducial markers and those that did not.

IN PRACTICE

“These findings suggest that the technical advantages in precision of radiotherapy delivery afforded by [MRI-guided] SBRT translate to measurable clinical benefit,” the authors concluded. Potential reasons for the reduced risk of acute toxicity with the MRI-guided approach include “daily online adaptive planning, MRI‐based contouring that results in smaller treatment volumes, and MRI tracking, all of which may facilitate the precision and accuracy of treatment delivery.”

SOURCE

The study was led by Jonathan Leeman, MD, of the Dana-Farber Cancer Institute, Boston, and was published July 24 in Cancer.

LIMITATIONS

• The analysis did not account for differences in dosimetry, radiation planning, and toxicity management and assessment between the studies.
• Late toxicity and cancer control rates were not tracked and may have differed between the two approaches.

DISCLOSURES

• No external funding was reported.
• The investigators reported grants and consulting, personal, and other payments from Novartis, AstraZeneca, Janssen, and other companies.

A version of this article appeared on Medscape.com.

Topline

The risk of venous thromboembolism is so high during neoadjuvant chemotherapy for advanced epithelial ovarian cancer that routine thromboprophylaxis may be warranted.

Methodology

• Investigators reviewed 154 consecutive cases of advanced stage epithelial ovarian cancer treated with neoadjuvant chemotherapy and interval cytoreductive surgery at the Mayo Clinic in Rochester, Minn.
• Their goal was to assess the incidence, timing, and risk factors for venous thromboembolism (VTE) from diagnosis through 6 months following surgery.
• VTEs were discovered due to symptoms, not screening.

Takeaways

• Overall, 33 women (21.4%) developed VTEs; 22 VTEs (66.67%) occurred between diagnosis and surgery; 4 (12.12%) were present at diagnosis, and 7 (21.21%) occurred after surgery.
• The researchers observed no statistically significant differences in risk factors – which included age, body mass index, functional status, histology, Khorana score, and smoking history – between women who did and did not develop a VTE.
• In the cohort, 11 women (33.3%) received a direct-acting oral anticoagulant (DOAC) to treat a VTE between VTE diagnosis and 180 days after interval cytoreductive surgery.  
• There were no significant differences in the number of intraoperative blood transfusions, blood loss, or bleeding complications between women who received and did not receive a DOAC.

In practice

The current study suggests that “two-thirds [of VTEs] may have been preventable” because they occurred between epithelial ovarian cancer diagnosis and interval cytoreductive surgery, the authors wrote. “Our study, like others, did not elucidate specific risk criteria in patients with advanced stage [epithelial ovarian cancer] who do and do not need thromboprophylaxis – begging the question that perhaps they all need thromboprophylaxis.”

Source

The work, led by Anousheh Shafa, MD, of Mayo Clinic’s department of obstetrics and gynecology, was published online in Gynecologic Oncology.  

Limitations

• The study was retrospective and had a small sample size.
• The study was not powered to identify risk factors associated with an increased risk of VTE.
• At Mayo Clinic, neoadjuvant chemotherapy is reserved for patients with large-volume or unresectable disease, poor nutritional status, or poor performance status; the data may not be as applicable in centers with different triage criteria for receiving neoadjuvant chemotherapy.

Disclosures:

Disclosures and funding sources were not reported.
 

A version of this article appeared on Medscape.com.

Topline

The risk of venous thromboembolism is so high during neoadjuvant chemotherapy for advanced epithelial ovarian cancer that routine thromboprophylaxis may be warranted.

Methodology

• Investigators reviewed 154 consecutive cases of advanced stage epithelial ovarian cancer treated with neoadjuvant chemotherapy and interval cytoreductive surgery at the Mayo Clinic in Rochester, Minn.
• Their goal was to assess the incidence, timing, and risk factors for venous thromboembolism (VTE) from diagnosis through 6 months following surgery.
• VTEs were discovered due to symptoms, not screening.

Takeaways

• Overall, 33 women (21.4%) developed VTEs; 22 VTEs (66.67%) occurred between diagnosis and surgery; 4 (12.12%) were present at diagnosis, and 7 (21.21%) occurred after surgery.
• The researchers observed no statistically significant differences in risk factors – which included age, body mass index, functional status, histology, Khorana score, and smoking history – between women who did and did not develop a VTE.
• In the cohort, 11 women (33.3%) received a direct-acting oral anticoagulant (DOAC) to treat a VTE between VTE diagnosis and 180 days after interval cytoreductive surgery.  
• There were no significant differences in the number of intraoperative blood transfusions, blood loss, or bleeding complications between women who received and did not receive a DOAC.

In practice

The current study suggests that “two-thirds [of VTEs] may have been preventable” because they occurred between epithelial ovarian cancer diagnosis and interval cytoreductive surgery, the authors wrote. “Our study, like others, did not elucidate specific risk criteria in patients with advanced stage [epithelial ovarian cancer] who do and do not need thromboprophylaxis – begging the question that perhaps they all need thromboprophylaxis.”

Source

The work, led by Anousheh Shafa, MD, of Mayo Clinic’s department of obstetrics and gynecology, was published online in Gynecologic Oncology.  

Limitations

• The study was retrospective and had a small sample size.
• The study was not powered to identify risk factors associated with an increased risk of VTE.
• At Mayo Clinic, neoadjuvant chemotherapy is reserved for patients with large-volume or unresectable disease, poor nutritional status, or poor performance status; the data may not be as applicable in centers with different triage criteria for receiving neoadjuvant chemotherapy.

Disclosures:

Disclosures and funding sources were not reported.
 

A version of this article appeared on Medscape.com.

Topline

The risk of venous thromboembolism is so high during neoadjuvant chemotherapy for advanced epithelial ovarian cancer that routine thromboprophylaxis may be warranted.

Methodology

• Investigators reviewed 154 consecutive cases of advanced stage epithelial ovarian cancer treated with neoadjuvant chemotherapy and interval cytoreductive surgery at the Mayo Clinic in Rochester, Minn.
• Their goal was to assess the incidence, timing, and risk factors for venous thromboembolism (VTE) from diagnosis through 6 months following surgery.
• VTEs were discovered due to symptoms, not screening.

Takeaways

• Overall, 33 women (21.4%) developed VTEs; 22 VTEs (66.67%) occurred between diagnosis and surgery; 4 (12.12%) were present at diagnosis, and 7 (21.21%) occurred after surgery.
• The researchers observed no statistically significant differences in risk factors – which included age, body mass index, functional status, histology, Khorana score, and smoking history – between women who did and did not develop a VTE.
• In the cohort, 11 women (33.3%) received a direct-acting oral anticoagulant (DOAC) to treat a VTE between VTE diagnosis and 180 days after interval cytoreductive surgery.  
• There were no significant differences in the number of intraoperative blood transfusions, blood loss, or bleeding complications between women who received and did not receive a DOAC.

In practice

The current study suggests that “two-thirds [of VTEs] may have been preventable” because they occurred between epithelial ovarian cancer diagnosis and interval cytoreductive surgery, the authors wrote. “Our study, like others, did not elucidate specific risk criteria in patients with advanced stage [epithelial ovarian cancer] who do and do not need thromboprophylaxis – begging the question that perhaps they all need thromboprophylaxis.”

Source

The work, led by Anousheh Shafa, MD, of Mayo Clinic’s department of obstetrics and gynecology, was published online in Gynecologic Oncology.  

Limitations

• The study was retrospective and had a small sample size.
• The study was not powered to identify risk factors associated with an increased risk of VTE.
• At Mayo Clinic, neoadjuvant chemotherapy is reserved for patients with large-volume or unresectable disease, poor nutritional status, or poor performance status; the data may not be as applicable in centers with different triage criteria for receiving neoadjuvant chemotherapy.

Disclosures:

Disclosures and funding sources were not reported.
 

A version of this article appeared on Medscape.com.

Topline

Short-course hypofractionated palliative radiation therapy improves quality of life in patients with poor-prognosis, high-grade gliomas.

Methodology

• Uncertainty persists about the value of palliative radiation, particularly longer regimens, among patients with high-grade gliomas. 
• To address the uncertainty, investigators administered quality of life (QoL) questionnaires to patients before receiving 35 Gy of palliative radiation in 10 fractions over 2 weeks, then again 1 month after treatment, followed by every 3 months until disease progression or death.
• Overall, 49 of 55 patients (89%) completed radiation treatment, and 42 completed the surveys. 
• QoL was assessed using the 100-point European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and its brain cancer module (BN20).
• Two-thirds of patients were treated with temozolomide chemotherapy following radiation.

Takeaways

• There was clinically and statistically significant improvement 1 month after radiation therapy in patient-reported fatigue and dyspnea on the QLQ-C30.
• A clinically meaningful improvement – meaning a 10-point or greater improvement – was seen for insomnia. Other symptoms, such as nausea/vomiting, loss of appetite, constipation, diarrhea, and financial difficulty, remained stable over time.
• On the BN20, investigators reported clinically and statistically significant improvement in motor function; other symptoms remained stable. 
• Median progression-free survival was 8.4 months; median overall survival was 10.5 months.

In practice

“Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis [high-grade glioma] does not impair QoL in the short term; but is rather associated with stable and/or improved QoL scores in several domains/symptom scales” at 1-3 months after treatment, “making it a viable resource-sparing alternative regimen,” the authors concluded.

Source

The work, led by Y. Baviskar of the Tata Memorial Hospital department of radiation oncology in Mumbai, India, was published July 11 in  Clinical Oncology.

Limitations

• It was a single-center study with no control arm.
• Fewer patients completed QoL forms over time, limiting longitudinal assessment to 3 months.
• Forms might have been completed by caregivers at times, raising questions about the veracity of responses.

Disclosures

• There was no external funding for the work.  
• The investigators report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Topline

Short-course hypofractionated palliative radiation therapy improves quality of life in patients with poor-prognosis, high-grade gliomas.

Methodology

• Uncertainty persists about the value of palliative radiation, particularly longer regimens, among patients with high-grade gliomas. 
• To address the uncertainty, investigators administered quality of life (QoL) questionnaires to patients before receiving 35 Gy of palliative radiation in 10 fractions over 2 weeks, then again 1 month after treatment, followed by every 3 months until disease progression or death.
• Overall, 49 of 55 patients (89%) completed radiation treatment, and 42 completed the surveys. 
• QoL was assessed using the 100-point European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and its brain cancer module (BN20).
• Two-thirds of patients were treated with temozolomide chemotherapy following radiation.

Takeaways

• There was clinically and statistically significant improvement 1 month after radiation therapy in patient-reported fatigue and dyspnea on the QLQ-C30.
• A clinically meaningful improvement – meaning a 10-point or greater improvement – was seen for insomnia. Other symptoms, such as nausea/vomiting, loss of appetite, constipation, diarrhea, and financial difficulty, remained stable over time.
• On the BN20, investigators reported clinically and statistically significant improvement in motor function; other symptoms remained stable. 
• Median progression-free survival was 8.4 months; median overall survival was 10.5 months.

In practice

“Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis [high-grade glioma] does not impair QoL in the short term; but is rather associated with stable and/or improved QoL scores in several domains/symptom scales” at 1-3 months after treatment, “making it a viable resource-sparing alternative regimen,” the authors concluded.

Source

The work, led by Y. Baviskar of the Tata Memorial Hospital department of radiation oncology in Mumbai, India, was published July 11 in  Clinical Oncology.

Limitations

• It was a single-center study with no control arm.
• Fewer patients completed QoL forms over time, limiting longitudinal assessment to 3 months.
• Forms might have been completed by caregivers at times, raising questions about the veracity of responses.

Disclosures

• There was no external funding for the work.  
• The investigators report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Topline

Short-course hypofractionated palliative radiation therapy improves quality of life in patients with poor-prognosis, high-grade gliomas.

Methodology

• Uncertainty persists about the value of palliative radiation, particularly longer regimens, among patients with high-grade gliomas. 
• To address the uncertainty, investigators administered quality of life (QoL) questionnaires to patients before receiving 35 Gy of palliative radiation in 10 fractions over 2 weeks, then again 1 month after treatment, followed by every 3 months until disease progression or death.
• Overall, 49 of 55 patients (89%) completed radiation treatment, and 42 completed the surveys. 
• QoL was assessed using the 100-point European Organization for Research and Treatment of Cancer QoL core questionnaire (QLQ-C30) and its brain cancer module (BN20).
• Two-thirds of patients were treated with temozolomide chemotherapy following radiation.

Takeaways

• There was clinically and statistically significant improvement 1 month after radiation therapy in patient-reported fatigue and dyspnea on the QLQ-C30.
• A clinically meaningful improvement – meaning a 10-point or greater improvement – was seen for insomnia. Other symptoms, such as nausea/vomiting, loss of appetite, constipation, diarrhea, and financial difficulty, remained stable over time.
• On the BN20, investigators reported clinically and statistically significant improvement in motor function; other symptoms remained stable. 
• Median progression-free survival was 8.4 months; median overall survival was 10.5 months.

In practice

“Short-course palliative hypofractionated radiotherapy in patients with poor-prognosis [high-grade glioma] does not impair QoL in the short term; but is rather associated with stable and/or improved QoL scores in several domains/symptom scales” at 1-3 months after treatment, “making it a viable resource-sparing alternative regimen,” the authors concluded.

Source

The work, led by Y. Baviskar of the Tata Memorial Hospital department of radiation oncology in Mumbai, India, was published July 11 in  Clinical Oncology.

Limitations

• It was a single-center study with no control arm.
• Fewer patients completed QoL forms over time, limiting longitudinal assessment to 3 months.
• Forms might have been completed by caregivers at times, raising questions about the veracity of responses.

Disclosures

• There was no external funding for the work.  
• The investigators report no relevant financial relationships.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved quizartinib (Vanflyta) for adults with acute myeloid leukemia (AML) that carries the FLT3-ITD genetic mutation.

On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.

The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.

The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation. 

Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).

Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.

Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”

The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.

Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”

In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.

The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.

In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.

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

The Food and Drug Administration has approved quizartinib (Vanflyta) for adults with acute myeloid leukemia (AML) that carries the FLT3-ITD genetic mutation.

On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.

The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.

The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation. 

Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).

Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.

Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”

The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.

Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”

In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.

The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.

In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.

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

The Food and Drug Administration has approved quizartinib (Vanflyta) for adults with acute myeloid leukemia (AML) that carries the FLT3-ITD genetic mutation.

On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.

The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.

The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation. 

Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).

Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.

Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”

The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.

Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”

In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.

The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.

In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.

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

Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.

A team of British investigators are now reporting a new strategy to help lessen this problem.

In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.

Overall, the findings show “DO-IMRT improves patient-reported swallowing function, compared with standard IMRT,” said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”

The team reported the results of their phase 3 trial in The Lancet Oncology.

Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.

Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.

In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.

Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.

At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.

The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.

DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.

At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.

The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).

Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.

In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.

Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”

The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.

For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.

The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.

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

Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.

A team of British investigators are now reporting a new strategy to help lessen this problem.

In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.

Overall, the findings show “DO-IMRT improves patient-reported swallowing function, compared with standard IMRT,” said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”

The team reported the results of their phase 3 trial in The Lancet Oncology.

Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.

Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.

In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.

Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.

At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.

The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.

DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.

At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.

The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).

Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.

In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.

Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”

The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.

For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.

The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.

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

Dysphagia is one of the most common side effects of radiation for head and neck cancer and can be so bad that patients require a permanent gastrostomy tube for feeding.

A team of British investigators are now reporting a new strategy to help lessen this problem.

In the trial, the approach – dubbed dysphagia-optimized intensity-modulated radiotherapy (DO-IMRT) – reduced incidental radiation to the pharyngeal constrictor muscles responsible for swallowing during IMRT for pharyngeal cancer. Patients randomized to DO-IMRT reported significant improvements in swallowing at 1 year, compared with those receiving standard IMRT, at no cost to oncologic outcomes.

Overall, the findings show “DO-IMRT improves patient-reported swallowing function, compared with standard IMRT,” said investigators led by Christopher Nutting, MD, PhD, a head and neck cancer specialist at the Royal Marsden Hospital, London. “DO-IMRT should be considered a new standard of care.”

The team reported the results of their phase 3 trial in The Lancet Oncology.

Swallowing issues affect most patients with head and neck cancer after radiation therapy but strategies to mitigate this long-term adverse effect remain limited.

Dr. Nutting and colleagues wanted to assess whether a novel approach to radiation therapy could reduce the swallowing problems patients often encounter.

In the trial, 112 subjects with T1-4, N0-3, M0 oropharyngeal (90%) or hypopharyngeal cancer (10%) were randomized to standard IMRT or DO-IMRT. Patients received care at 22 radiation therapy centers in Ireland and the UK from 2016 to 2018.

Patients got radiation in 30 fractions over 6 weeks; most also had chemotherapy. The standard IMRT group received 65 Gy to their primary and nodal tumors and 54 Gy to other pharyngeal and nodal areas. In the DO-IMRT group, radiation doses to pharyngeal constrictor muscles lying outside of the tumor target area were limited to 50 Gy.

At 1 year, 56 patients randomized to DO-IMRT scored, on average, 7.2 points higher than the 56 patients randomized to standard IMRT – 77.7 points vs. 70.6 (P = .037) – on the 100-point MD Anderson Dysphagia Inventory (MDADI). MDADI is a validated scale for tracking radiation-induced dysphagia, with higher scores indicating better swallowing function.

The difference grew to 9.8 points when adjusted for chemotherapy use and tumor location and stage.

DO-IMRT patients were also more likely to report eating their normal diet and dining in public. Speech and language therapists who, like patients, were blinded to treatment allocation, reported better outcomes among patients receiving DO-IMRT as well.

At just over 3 years, oncologic outcomes were essentially equivalent in both groups. Two local recurrences occurred in both arms; distant metastatic recurrences occurred in three patients in the DO-IMRT group and two in the standard IMRT group.

The most common grade 3-4 late adverse events were hearing impairment (16% with DO-IMRT vs. 13% with standard IMRT), dry mouth (5% vs. 15%), and dysphagia (5% vs. 15%).

Taken together, the findings indicate that reducing doses to the pharyngeal constrictor muscle translates to “a meaningful benefit for patients” in terms of improved swallowing function, the investigators said.

In an accompanying editorial, Sandra Nuyts, MD, PhD, noted, however, that the trial failed to meet the predefined threshold for clinical significance, a 10-point difference in MDADI scores.

Still, “several other patient-reported and physician-reported secondary endpoints favored DO-IMRT,” explained Dr. Nuyts, a radiation oncologist at the Leuven Cancer Institute, Belgium. Considered alongside positive reports from smaller, nonrandomized studies, “there is now compelling evidence that the risk of dysphagia after head and neck radiotherapy can be reduced with this technology, without increasing the risk of local recurrences.”

The study team and Dr. Nuyts both called for further refinement of the technique, particularly figuring out what specific sections of the constrictor muscles need to be spared to optimize outcomes.

For now, there is a limit on “how much organ sparing can be achieved with the current DO-IMRT technique” because “use of even narrower margins” around the tumor runs the risk of not treating it adequately, investigators said.

The study was funded by Cancer Research UK. Dr. Nutting reports stock options in Advanced Oncotherapy. Another investigator reports institutional grants from Varian, AstraZeneca, Roche, and other companies. Dr. Nuyts reports no relevant financial relationships.

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

TOPLINE:

Although practice patterns vary widely, modified, reduced-dose FOLFIRINOX is as effective as standard, full-dose regimens for patients with metastatic pancreatic cancer in the first-line setting, and it is less likely to cause febrile neutropenia.

METHODOLOGY:

• No randomized controlled trials have directly compared modified FOLFIRINOX to standard FOLFIRINOX; this meta-analysis aims to fill the evidence gap.
• The investigators winnowed hundreds of first-line FOLFIRINOX studies down to 37 – 11 prospective and 26 retrospective analyses – to assess practice patterns and clinical outcomes.
• Dose information was grouped into four categories: planned dose in the standard FOLFIRINOX group; actual administered dose in the standard group; planned dose in the modified group; actual administered dose in the modified group.

TAKEAWAY:

• There were 12 types of “planned” dose reductions in FOLFIRINOX: 75%-100% oxaliplatin, 75%-100% irinotecan, 0%-100% 5-fluorouracil (5-FU) bolus, and 75%-133% 5-FU continuous injection.
• Doses actually delivered fell further to 54%-96% for oxaliplatin, 61%-88% for irinotecan, 0%-92% for 5-FU bolus, and 63%-98% 5-FU continuous injection.
• Despite the variations in dosing, reduced doses of FOLFIRINOX were associated with a slightly but not significantly higher objective response rate: 33.8% versus 28.2% for standard dosing (P = .1).
• The incidence of febrile neutropenia was significantly lower in the reduced-dose groups: 5.5% with modified FOLFIRINOX versus 11.6% with standard (P = .03).

IN PRACTICE:

Although the study supports reduced-dose regimens, it also shows that there is “still no consensus” on appropriate dose modification, the authors said. “The best dose modification protocol” remains to be determined and standardized for metastatic pancreatic cancer.

SOURCE:

The study was led by Kwangrok Jung at Seoul (South Korea) National University, and was published June 29 in Therapeutic Advances in Medical Oncology.

LIMITATIONS:

• Only 11 of the 37 studies were prospective.
• The studies often lacked key information, including the reason for dose reductions or detailed dose reduction protocols.
• Studies were also inconsistent in how they reported FOLFIRINOX dose modifications.

DISCLOSURES:

There was no funding for the study, and the investigators had no disclosures.

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

TOPLINE:

Although practice patterns vary widely, modified, reduced-dose FOLFIRINOX is as effective as standard, full-dose regimens for patients with metastatic pancreatic cancer in the first-line setting, and it is less likely to cause febrile neutropenia.

METHODOLOGY:

• No randomized controlled trials have directly compared modified FOLFIRINOX to standard FOLFIRINOX; this meta-analysis aims to fill the evidence gap.
• The investigators winnowed hundreds of first-line FOLFIRINOX studies down to 37 – 11 prospective and 26 retrospective analyses – to assess practice patterns and clinical outcomes.
• Dose information was grouped into four categories: planned dose in the standard FOLFIRINOX group; actual administered dose in the standard group; planned dose in the modified group; actual administered dose in the modified group.

TAKEAWAY:

• There were 12 types of “planned” dose reductions in FOLFIRINOX: 75%-100% oxaliplatin, 75%-100% irinotecan, 0%-100% 5-fluorouracil (5-FU) bolus, and 75%-133% 5-FU continuous injection.
• Doses actually delivered fell further to 54%-96% for oxaliplatin, 61%-88% for irinotecan, 0%-92% for 5-FU bolus, and 63%-98% 5-FU continuous injection.
• Despite the variations in dosing, reduced doses of FOLFIRINOX were associated with a slightly but not significantly higher objective response rate: 33.8% versus 28.2% for standard dosing (P = .1).
• The incidence of febrile neutropenia was significantly lower in the reduced-dose groups: 5.5% with modified FOLFIRINOX versus 11.6% with standard (P = .03).

IN PRACTICE:

Although the study supports reduced-dose regimens, it also shows that there is “still no consensus” on appropriate dose modification, the authors said. “The best dose modification protocol” remains to be determined and standardized for metastatic pancreatic cancer.

SOURCE:

The study was led by Kwangrok Jung at Seoul (South Korea) National University, and was published June 29 in Therapeutic Advances in Medical Oncology.

LIMITATIONS:

• Only 11 of the 37 studies were prospective.
• The studies often lacked key information, including the reason for dose reductions or detailed dose reduction protocols.
• Studies were also inconsistent in how they reported FOLFIRINOX dose modifications.

DISCLOSURES:

There was no funding for the study, and the investigators had no disclosures.

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

TOPLINE:

Although practice patterns vary widely, modified, reduced-dose FOLFIRINOX is as effective as standard, full-dose regimens for patients with metastatic pancreatic cancer in the first-line setting, and it is less likely to cause febrile neutropenia.

METHODOLOGY:

• No randomized controlled trials have directly compared modified FOLFIRINOX to standard FOLFIRINOX; this meta-analysis aims to fill the evidence gap.
• The investigators winnowed hundreds of first-line FOLFIRINOX studies down to 37 – 11 prospective and 26 retrospective analyses – to assess practice patterns and clinical outcomes.
• Dose information was grouped into four categories: planned dose in the standard FOLFIRINOX group; actual administered dose in the standard group; planned dose in the modified group; actual administered dose in the modified group.

TAKEAWAY:

• There were 12 types of “planned” dose reductions in FOLFIRINOX: 75%-100% oxaliplatin, 75%-100% irinotecan, 0%-100% 5-fluorouracil (5-FU) bolus, and 75%-133% 5-FU continuous injection.
• Doses actually delivered fell further to 54%-96% for oxaliplatin, 61%-88% for irinotecan, 0%-92% for 5-FU bolus, and 63%-98% 5-FU continuous injection.
• Despite the variations in dosing, reduced doses of FOLFIRINOX were associated with a slightly but not significantly higher objective response rate: 33.8% versus 28.2% for standard dosing (P = .1).
• The incidence of febrile neutropenia was significantly lower in the reduced-dose groups: 5.5% with modified FOLFIRINOX versus 11.6% with standard (P = .03).

IN PRACTICE:

Although the study supports reduced-dose regimens, it also shows that there is “still no consensus” on appropriate dose modification, the authors said. “The best dose modification protocol” remains to be determined and standardized for metastatic pancreatic cancer.

SOURCE:

The study was led by Kwangrok Jung at Seoul (South Korea) National University, and was published June 29 in Therapeutic Advances in Medical Oncology.

LIMITATIONS:

• Only 11 of the 37 studies were prospective.
• The studies often lacked key information, including the reason for dose reductions or detailed dose reduction protocols.
• Studies were also inconsistent in how they reported FOLFIRINOX dose modifications.

DISCLOSURES:

There was no funding for the study, and the investigators had no disclosures.

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

The results of a phase 3 trial that assessed the use of a highly selective, potent oral vascular endothelial growth factor receptor (VEGFR) inhibitor for patients with refractory metastatic colorectal cancer (CRC) were recently published.

The trial, dubbed FRESCO-2, found that use of fruquintinib “resulted in a significant and clinically meaningful benefit in overall survival, compared with placebo in patients with refractory metastatic colorectal cancer.”

More specifically, the median overall survival benefit was 2.6 months – 7.4 months with fruquintinib versus 4.8 months with placebo – among 691 heavily pretreated adults with metastatic colorectal adenocarcinoma. The difference translated to a 34% reduction in the risk of death with fruquintinib at a median follow-up of about 11 months.

These patients had received “all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib,” a less-selective VEGF inhibitor, according to investigators led by Arvind Dasari, MD, from the University of Texas MD Anderson Cancer Center, Houston.

Dr. Dasari and colleagues celebrated the results, stressing that “these data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer.”

The VEGF inhibitor has been approved in China for refractory metastatic CRC since 2018, and the recent phase 3 findings support the bid for Food and Drug Administration approval for this indication. The FDA granted fruquintinib priority review in May 2023.

However, in a tweet, Vinay Prasad, MD, an oncologist/epidemiologist at the University of California, San Francisco, who is an outspoken critic of the pharmaceutical industry, called the trial design “unethical.”

Fruquintinib, he explained, was compared with placebo, not investigators’ choice of treatment for patients dying of CRC.

Trial participants were considered to have refractory cases of CRC after previous lines of systemic treatment had failed. For almost three quarters of patients, more than three lines of therapy had failed, and patients still had options, including fluorouracil (5FU), oxaliplatin, or irinotecan, Dr. Prasad argued.

“Everyone who treats CRC would pull [their] mom off the trial and give 5FU and [bevacizumab] or IrOx [irinotecan plus oxaliplatin] or FOLFOX again, perhaps slightly differently,” Dr. Prasad said.

The “proof is they give [these drugs] post progression,” he continued. “After the control arm patients progressed, many doctors did try” these other options.

Hutchmed, the Hong Kong maker of fruquintinib, which sponsored the trial, did not respond to questions from this news organization about why the trial was designed with a placebo arm instead of investigators’ choice of treatment.

However, CRC specialist Alan Venook, MD, who was not involved in the trial, weighed in. He explained that he understands Dr. Prasad’s concerns but doesn’t necessarily think the trial was unethical.

For patients such as those in FRESCO-2, the impact of current treatment options is “so minimal” that forgoing active drug treatment is “not crazy,” said Dr. Venook, a medical oncologist at UCSF.

“If your chances of getting benefit are 1 in 20 and you are much more likely to get toxicity than benefit, you could argue” that having a placebo control arm in the trial is ethical, provided people understand what they are getting into, Dr. Venook said.

In the trial, almost two thirds of patients who received fruquintinib had grade 3 or worse toxicities, compared with half of placebo patients. The most common were hypertension (14% with fruquintinib vs. 1% with placebo), asthenia (8% vs. 4%), and hand-foot syndrome (6% vs. 0%).

Part of the risk-benefit assessment may also include weighing the estimated costs of fruquintinib against the 2.6-month median overall survival benefit.

“One could debate if 2.6 months of more time is worth the medication getting regulatory approval, or debate pricing when it’s approved, or delve closely into toxicity and quality of life data,” tweeted medical oncologist Temidayo Fadelu, MD, MPH, of Dana-Farber Cancer Center and Harvard Medical School, Boston, in response to Dr. Prasad’s thread. However, like Dr. Venook, Dr. Fadelu did not consider the trial design or the way the trial was conducted to be unethical.

Dr. Venook added that a treatment break is also not out of the question in this context. Some might even say that, given the risk-benefit ratio of current options, a temporary break from treatment “is the right thing to do.”

The study was funded by Hutchmed. The investigators reported ties to Hutchmed and other pharmaceutical companies. Dr. Dasari reported grants, contracts, speaker’s fees, and other payments from Hutchmed and other companies. Dr. Venook disclosed no relevant financial relationships.

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

The results of a phase 3 trial that assessed the use of a highly selective, potent oral vascular endothelial growth factor receptor (VEGFR) inhibitor for patients with refractory metastatic colorectal cancer (CRC) were recently published.

The trial, dubbed FRESCO-2, found that use of fruquintinib “resulted in a significant and clinically meaningful benefit in overall survival, compared with placebo in patients with refractory metastatic colorectal cancer.”

More specifically, the median overall survival benefit was 2.6 months – 7.4 months with fruquintinib versus 4.8 months with placebo – among 691 heavily pretreated adults with metastatic colorectal adenocarcinoma. The difference translated to a 34% reduction in the risk of death with fruquintinib at a median follow-up of about 11 months.

These patients had received “all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib,” a less-selective VEGF inhibitor, according to investigators led by Arvind Dasari, MD, from the University of Texas MD Anderson Cancer Center, Houston.

Dr. Dasari and colleagues celebrated the results, stressing that “these data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer.”

The VEGF inhibitor has been approved in China for refractory metastatic CRC since 2018, and the recent phase 3 findings support the bid for Food and Drug Administration approval for this indication. The FDA granted fruquintinib priority review in May 2023.

However, in a tweet, Vinay Prasad, MD, an oncologist/epidemiologist at the University of California, San Francisco, who is an outspoken critic of the pharmaceutical industry, called the trial design “unethical.”

Fruquintinib, he explained, was compared with placebo, not investigators’ choice of treatment for patients dying of CRC.

Trial participants were considered to have refractory cases of CRC after previous lines of systemic treatment had failed. For almost three quarters of patients, more than three lines of therapy had failed, and patients still had options, including fluorouracil (5FU), oxaliplatin, or irinotecan, Dr. Prasad argued.

“Everyone who treats CRC would pull [their] mom off the trial and give 5FU and [bevacizumab] or IrOx [irinotecan plus oxaliplatin] or FOLFOX again, perhaps slightly differently,” Dr. Prasad said.

The “proof is they give [these drugs] post progression,” he continued. “After the control arm patients progressed, many doctors did try” these other options.

Hutchmed, the Hong Kong maker of fruquintinib, which sponsored the trial, did not respond to questions from this news organization about why the trial was designed with a placebo arm instead of investigators’ choice of treatment.

However, CRC specialist Alan Venook, MD, who was not involved in the trial, weighed in. He explained that he understands Dr. Prasad’s concerns but doesn’t necessarily think the trial was unethical.

For patients such as those in FRESCO-2, the impact of current treatment options is “so minimal” that forgoing active drug treatment is “not crazy,” said Dr. Venook, a medical oncologist at UCSF.

“If your chances of getting benefit are 1 in 20 and you are much more likely to get toxicity than benefit, you could argue” that having a placebo control arm in the trial is ethical, provided people understand what they are getting into, Dr. Venook said.

In the trial, almost two thirds of patients who received fruquintinib had grade 3 or worse toxicities, compared with half of placebo patients. The most common were hypertension (14% with fruquintinib vs. 1% with placebo), asthenia (8% vs. 4%), and hand-foot syndrome (6% vs. 0%).

Part of the risk-benefit assessment may also include weighing the estimated costs of fruquintinib against the 2.6-month median overall survival benefit.

“One could debate if 2.6 months of more time is worth the medication getting regulatory approval, or debate pricing when it’s approved, or delve closely into toxicity and quality of life data,” tweeted medical oncologist Temidayo Fadelu, MD, MPH, of Dana-Farber Cancer Center and Harvard Medical School, Boston, in response to Dr. Prasad’s thread. However, like Dr. Venook, Dr. Fadelu did not consider the trial design or the way the trial was conducted to be unethical.

Dr. Venook added that a treatment break is also not out of the question in this context. Some might even say that, given the risk-benefit ratio of current options, a temporary break from treatment “is the right thing to do.”

The study was funded by Hutchmed. The investigators reported ties to Hutchmed and other pharmaceutical companies. Dr. Dasari reported grants, contracts, speaker’s fees, and other payments from Hutchmed and other companies. Dr. Venook disclosed no relevant financial relationships.

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

The results of a phase 3 trial that assessed the use of a highly selective, potent oral vascular endothelial growth factor receptor (VEGFR) inhibitor for patients with refractory metastatic colorectal cancer (CRC) were recently published.

The trial, dubbed FRESCO-2, found that use of fruquintinib “resulted in a significant and clinically meaningful benefit in overall survival, compared with placebo in patients with refractory metastatic colorectal cancer.”

More specifically, the median overall survival benefit was 2.6 months – 7.4 months with fruquintinib versus 4.8 months with placebo – among 691 heavily pretreated adults with metastatic colorectal adenocarcinoma. The difference translated to a 34% reduction in the risk of death with fruquintinib at a median follow-up of about 11 months.

These patients had received “all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib,” a less-selective VEGF inhibitor, according to investigators led by Arvind Dasari, MD, from the University of Texas MD Anderson Cancer Center, Houston.

Dr. Dasari and colleagues celebrated the results, stressing that “these data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer.”

The VEGF inhibitor has been approved in China for refractory metastatic CRC since 2018, and the recent phase 3 findings support the bid for Food and Drug Administration approval for this indication. The FDA granted fruquintinib priority review in May 2023.

However, in a tweet, Vinay Prasad, MD, an oncologist/epidemiologist at the University of California, San Francisco, who is an outspoken critic of the pharmaceutical industry, called the trial design “unethical.”

Fruquintinib, he explained, was compared with placebo, not investigators’ choice of treatment for patients dying of CRC.

Trial participants were considered to have refractory cases of CRC after previous lines of systemic treatment had failed. For almost three quarters of patients, more than three lines of therapy had failed, and patients still had options, including fluorouracil (5FU), oxaliplatin, or irinotecan, Dr. Prasad argued.

“Everyone who treats CRC would pull [their] mom off the trial and give 5FU and [bevacizumab] or IrOx [irinotecan plus oxaliplatin] or FOLFOX again, perhaps slightly differently,” Dr. Prasad said.

The “proof is they give [these drugs] post progression,” he continued. “After the control arm patients progressed, many doctors did try” these other options.

Hutchmed, the Hong Kong maker of fruquintinib, which sponsored the trial, did not respond to questions from this news organization about why the trial was designed with a placebo arm instead of investigators’ choice of treatment.

However, CRC specialist Alan Venook, MD, who was not involved in the trial, weighed in. He explained that he understands Dr. Prasad’s concerns but doesn’t necessarily think the trial was unethical.

For patients such as those in FRESCO-2, the impact of current treatment options is “so minimal” that forgoing active drug treatment is “not crazy,” said Dr. Venook, a medical oncologist at UCSF.

“If your chances of getting benefit are 1 in 20 and you are much more likely to get toxicity than benefit, you could argue” that having a placebo control arm in the trial is ethical, provided people understand what they are getting into, Dr. Venook said.

In the trial, almost two thirds of patients who received fruquintinib had grade 3 or worse toxicities, compared with half of placebo patients. The most common were hypertension (14% with fruquintinib vs. 1% with placebo), asthenia (8% vs. 4%), and hand-foot syndrome (6% vs. 0%).

Part of the risk-benefit assessment may also include weighing the estimated costs of fruquintinib against the 2.6-month median overall survival benefit.

“One could debate if 2.6 months of more time is worth the medication getting regulatory approval, or debate pricing when it’s approved, or delve closely into toxicity and quality of life data,” tweeted medical oncologist Temidayo Fadelu, MD, MPH, of Dana-Farber Cancer Center and Harvard Medical School, Boston, in response to Dr. Prasad’s thread. However, like Dr. Venook, Dr. Fadelu did not consider the trial design or the way the trial was conducted to be unethical.

Dr. Venook added that a treatment break is also not out of the question in this context. Some might even say that, given the risk-benefit ratio of current options, a temporary break from treatment “is the right thing to do.”

The study was funded by Hutchmed. The investigators reported ties to Hutchmed and other pharmaceutical companies. Dr. Dasari reported grants, contracts, speaker’s fees, and other payments from Hutchmed and other companies. Dr. Venook disclosed no relevant financial relationships.

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

TOPLINE:

Irradiating a small number of metastatic lesions does not appear to improve progression-free or overall survival in patients receiving immune checkpoint inhibitor monotherapy for advanced cancer.

METHODOLOGY:

• In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
• Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
• Most patients had more than three lesions.
• Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.

TAKEAWAY:

• Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
• Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
• However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
• The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.

IN PRACTICE:

Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
 

SOURCE:

The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.

LIMITATIONS:

• There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
• More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.

DISCLOSURES:

The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.

Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.

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

TOPLINE:

Irradiating a small number of metastatic lesions does not appear to improve progression-free or overall survival in patients receiving immune checkpoint inhibitor monotherapy for advanced cancer.

METHODOLOGY:

• In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
• Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
• Most patients had more than three lesions.
• Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.

TAKEAWAY:

• Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
• Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
• However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
• The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.

IN PRACTICE:

Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
 

SOURCE:

The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.

LIMITATIONS:

• There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
• More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.

DISCLOSURES:

The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.

Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.

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

TOPLINE:

Irradiating a small number of metastatic lesions does not appear to improve progression-free or overall survival in patients receiving immune checkpoint inhibitor monotherapy for advanced cancer.

METHODOLOGY:

• In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
• Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
• Most patients had more than three lesions.
• Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.

TAKEAWAY:

• Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
• Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
• However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
• The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.

IN PRACTICE:

Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
 

SOURCE:

The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.

LIMITATIONS:

• There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
• More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.

DISCLOSURES:

The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.

Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.

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

TOPLINE:

Pembrolizumab doesn’t work as well for patients with metastatic non–small cell lung cancer (NSCLC) who have diabetes.

METHODOLOGY:

• Investigators reviewed the medical records of 203 consecutive patients with metastatic NSCLC who received first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center in Israel.
• Overall, 1 in 4 patients (n = 51) had diabetes mellitus; most (n = 42) were being treated with oral hypoglycemic agents, frequently metformin, and 7 were taking insulin.
• Rates of tumors with PD‐L1 expression above 50% were not significantly different among patients with diabetes and those without.

TAKEAWAY:

• Overall, among patients with diabetes, median progression-free survival (PFS) was significantly shorter than among patients without diabetes (5.9 vs. 7.1 months), as was overall survival (12 vs. 21 months).
• Shorter overall survival was more pronounced among those with diabetes who received pembrolizumab alone (12 vs. 27 months) in comparison with patients who received pembrolizumab plus chemotherapy (14.3 vs. 19.4 months).
• After adjusting for potential confounders, multivariate analysis confirmed that diabetes was an independent risk factor for shorter PFS (hazard ratio, 1.67) and shorter overall survival (HR, 1.73) for patients with NSCLC.
• In a validation cohort of 452 patients with metastatic NSCLC, only 19.6% of those with diabetes continued to take pembrolizumab at 12 months versus 31.7% of those without diabetes.

IN PRACTICE:

“As NSCLC patients with [diabetes] constitute a significant subgroup, there is an urgent need to validate our findings and explore whether outcomes in these patients can be improved by better glycemic control,” the authors said, adding that “chemotherapy may offset some of the deleterious effects” of diabetes.

SOURCE:

The study was led by Yasmin Leshem, MD, PhD, of the Tel Aviv Sourasky Medical Center, and was published in Cancer.

LIMITATIONS:

• Without access to blood test results outside the hospital, the researchers could not determine whether better glycemic control might have improved outcomes.
• The incidence of type 1 or 2 diabetes was not well documented.

DISCLOSURES:

• No funding source was reported.
• Two investigators reported receiving consulting and/or other fees from Bristol-Myers Squibb, Roche, Merck, Novartis, and Merck Sharp and Dohme.

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

TOPLINE:

Pembrolizumab doesn’t work as well for patients with metastatic non–small cell lung cancer (NSCLC) who have diabetes.

METHODOLOGY:

• Investigators reviewed the medical records of 203 consecutive patients with metastatic NSCLC who received first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center in Israel.
• Overall, 1 in 4 patients (n = 51) had diabetes mellitus; most (n = 42) were being treated with oral hypoglycemic agents, frequently metformin, and 7 were taking insulin.
• Rates of tumors with PD‐L1 expression above 50% were not significantly different among patients with diabetes and those without.

TAKEAWAY:

• Overall, among patients with diabetes, median progression-free survival (PFS) was significantly shorter than among patients without diabetes (5.9 vs. 7.1 months), as was overall survival (12 vs. 21 months).
• Shorter overall survival was more pronounced among those with diabetes who received pembrolizumab alone (12 vs. 27 months) in comparison with patients who received pembrolizumab plus chemotherapy (14.3 vs. 19.4 months).
• After adjusting for potential confounders, multivariate analysis confirmed that diabetes was an independent risk factor for shorter PFS (hazard ratio, 1.67) and shorter overall survival (HR, 1.73) for patients with NSCLC.
• In a validation cohort of 452 patients with metastatic NSCLC, only 19.6% of those with diabetes continued to take pembrolizumab at 12 months versus 31.7% of those without diabetes.

IN PRACTICE:

“As NSCLC patients with [diabetes] constitute a significant subgroup, there is an urgent need to validate our findings and explore whether outcomes in these patients can be improved by better glycemic control,” the authors said, adding that “chemotherapy may offset some of the deleterious effects” of diabetes.

SOURCE:

The study was led by Yasmin Leshem, MD, PhD, of the Tel Aviv Sourasky Medical Center, and was published in Cancer.

LIMITATIONS:

• Without access to blood test results outside the hospital, the researchers could not determine whether better glycemic control might have improved outcomes.
• The incidence of type 1 or 2 diabetes was not well documented.

DISCLOSURES:

• No funding source was reported.
• Two investigators reported receiving consulting and/or other fees from Bristol-Myers Squibb, Roche, Merck, Novartis, and Merck Sharp and Dohme.

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

TOPLINE:

Pembrolizumab doesn’t work as well for patients with metastatic non–small cell lung cancer (NSCLC) who have diabetes.

METHODOLOGY:

• Investigators reviewed the medical records of 203 consecutive patients with metastatic NSCLC who received first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center in Israel.
• Overall, 1 in 4 patients (n = 51) had diabetes mellitus; most (n = 42) were being treated with oral hypoglycemic agents, frequently metformin, and 7 were taking insulin.
• Rates of tumors with PD‐L1 expression above 50% were not significantly different among patients with diabetes and those without.

TAKEAWAY:

• Overall, among patients with diabetes, median progression-free survival (PFS) was significantly shorter than among patients without diabetes (5.9 vs. 7.1 months), as was overall survival (12 vs. 21 months).
• Shorter overall survival was more pronounced among those with diabetes who received pembrolizumab alone (12 vs. 27 months) in comparison with patients who received pembrolizumab plus chemotherapy (14.3 vs. 19.4 months).
• After adjusting for potential confounders, multivariate analysis confirmed that diabetes was an independent risk factor for shorter PFS (hazard ratio, 1.67) and shorter overall survival (HR, 1.73) for patients with NSCLC.
• In a validation cohort of 452 patients with metastatic NSCLC, only 19.6% of those with diabetes continued to take pembrolizumab at 12 months versus 31.7% of those without diabetes.

IN PRACTICE:

“As NSCLC patients with [diabetes] constitute a significant subgroup, there is an urgent need to validate our findings and explore whether outcomes in these patients can be improved by better glycemic control,” the authors said, adding that “chemotherapy may offset some of the deleterious effects” of diabetes.

SOURCE:

The study was led by Yasmin Leshem, MD, PhD, of the Tel Aviv Sourasky Medical Center, and was published in Cancer.

LIMITATIONS:

• Without access to blood test results outside the hospital, the researchers could not determine whether better glycemic control might have improved outcomes.
• The incidence of type 1 or 2 diabetes was not well documented.

DISCLOSURES:

• No funding source was reported.
• Two investigators reported receiving consulting and/or other fees from Bristol-Myers Squibb, Roche, Merck, Novartis, and Merck Sharp and Dohme.

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