Cancer

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

CHICAGO – Progress in breast cancer treatment over the past 2 decades has reduced expected mortality from both early-stage and metastatic disease, according to a new model that looked at 10-year distant recurrence-free survival and survival time after metastatic diagnosis, among other factors.

“There has been an accelerating influx of new treatments for breast cancer starting around 1990. We wished to ask whether and to what extent decades of metastatic treatment advances may have affected population level breast cancer mortality,” said Jennifer Lee Caswell-Jin, MD, during a presentation of the study at the annual meeting of the American Society of Clinical Oncology.

“Our models find that metastatic treatments improved population-level survival in all breast cancer subtypes since 2000 with substantial variability by subtype," said Dr. Caswell-Jin, who is a medical oncologist with Stanford (Calif.) Medicine specializing in breast cancer.

The study is based on an analysis of four models from the Cancer Intervention and Surveillance Modeling Network (CISNET). The models simulated breast cancer mortality between 2000 and 2019 factoring in the use of mammography, efficacy and dissemination of estrogen receptor (ER) and HER2-specific treatments of early-stage (stages I-III) and metastatic (stage IV or distant recurrence) disease, but also non–cancer-related mortality. The models compared overall and ER/HER2-specific breast cancer mortality rates during this period with estimated rates with no screening or treatment, and then attributed mortality reductions to screening, early-stage, or metastatic treatment.

The results were compared with three clinical trials that tested therapies in different subtypes of metastatic disease. Dr. Caswell-Jin and colleagues adjusted the analysis to reflect expected differences between clinical trial populations and the broader population by sampling simulated patients who resembled the trial population.

The investigators found that, at 71%, the biggest drop in mortality rates were for women with ER+/HER2+ breast cancer, followed by 61% for women with ER-/HER2+ breast cancer and 59% for women with ER+/HER2– breast cancer. Triple-negative breast cancer – one of the most challenging breast cancers to treat – only saw a drop of 40% during this period. About 19% of the overall reduction in breast cancer mortality were caused by treatments after metastasis.

The median survival after a diagnosis of ER+/HER2– metastatic recurrence increased from 2 years in 2000 to 3.5 years in 2019. In triple-negative breast cancer, the increase was more modest, from 1.2 years in 2000 to 1.8 years in 2019. After a diagnosis of metastatic recurrence of ER+/HER2+ breast cancer, median survival increased from 2.3 years in 2000 to 4.8 years in 2019, and for ER–/HER2+ breast cancer, from 2.2 years in 2000 to 3.9 years in 2019.

“How much metastatic treatments contributed to the overall mortality reduction varied over time depending on what therapies were entering the metastatic setting at that time and what therapies were transitioning from the metastatic to early-stage setting,” Dr. Caswell-Jin said.

The study did not include sacituzumab govitecan for metastatic triple-negative breast cancer, or trastuzumab deruxtecan and tucatinib for HER2-positive disease, which were approved after 2020. “The numbers that we cite will be better today for triple-negative breast cancer because of those two drugs. And will be even better for HER2-positive breast cancer because of those two drugs,” she said.

During the Q&A portion of the presentation, Daniel Hayes, MD, the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center, Ann Arbor, asked about the potential of CISNET as an in-practice diagnostic tool.

“We’ve traditionally told patients who have metastatic disease that they will not be cured. I told two patients that on Tuesday. Can CISNET modeling let us begin to see if there is indeed now, with the improved therapies we have, a group of patients who do appear to be cured, or is that not possible?” he asked.

Perhaps, Dr. Caswell-Jin said, in a very small population of older patients with HER2-positive breast cancer that did in fact occur, but to a very small degree.

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

The combination of neoadjuvant chemotherapy with immunotherapy led to significant improvements in survival for patients with resectable stage IIIA-B non–small cell lung cancer (NSCLC), according to researchers reporting earlier this month in Chicago at the annual meeting of the American Society of Clinical Oncology.

Advanced stage IIIA NSCLC is incurable in most patients with lung cancer, and with existing treatments only 30% of patients will live up to 5 years. In this study, neoadjuvant chemotherapy with nivolumab significantly increased the pathological complete response rate in 36.2% of patients, compared with 6.8% who received chemo alone, said study author Mariano Provencio-Pulla, MD, PhD, Instituto Investigacion Sanitaria Puerta de Hierro-Segovia de Arana, Spain. The major pathologic response (MPR) – which accounts for residual viable tumor of less than or equal to 10 – was better in the treatment group as compared with patients who received chemotherapy alone (52% vs 14%). The objective response rate (ORR) – or, the percentage of patients who had a partial or complete response to treatment – was 74% in the treatment group, compared with 48% among patients who received chemotherapy.

“In our opinion this should be the standard of care for patients,” Dr. Provencio-Pulla said during his presentation.

The ASCO treatment guidelines for stage III NSCLC, specify that some patients can receive immunotherapy for up to a year, but for resectable stage III disease, this therapy is still under investigation.

In this study, called NADIM II (NCT03838159), investigators enrolled 87 patients with resectable clinical stage IIIA disease between February 2019 and November 2021. NADIM II is an open-label, randomized, two-arm, phase 2, multicenter clinical trial. Patients had ECOG scores of 0-1 and no known EGFR/ALK alterations. Patients received either nivolumab 360 mg with paclitaxel 200 mg/m² and carboplatin AUC5 for three cycles every 21 days as treatment before or after surgery. Patients who received a resection that left no microscopic tumor in the primary tumor bed, received adjuvant nivolumab between weeks 3 and 8 after surgery for 6 months.

At 91%, almost all patients who received the immunotherapy and chemotherapy treatment underwent surgery, compared with 69% of patients in the chemotherapy treatment group. In the treatment group, patients with pathological complete response (pCR) had higher PD-L1 tumor proportion score (TPS) scores (median 70%).

The primary endpoint was pathological complete response of 0% viable tumor cells in resected lung and lymph nodes. The major pathological response was no more than 10% viable tumor remaining. The secondary endpoints included overall response rate, toxicity profile, and potential predictive biomarkers.

The addition of neoadjuvant nivolumab to chemotherapy significantly improved pCR (odds ratio, 7.88). The safety profile was “tolerable” with a moderate increase in grade 3-4 toxicity; plus no surgery was delayed because of problems with the treatment, Dr. Provencio-Pulla said.

This study was funded by Fundación GECP. Dr. Provencio-Pulla has received funding from Bristol-Myers Squibb, the maker of Opdivo (nivolumab).

Patients with locally advanced rectal cancer and tumors with deficient mismatch repair (dMMR) have shown a remarkable response to treatment with the programmed cell death-1 (PD-1) inhibitor dostarlimab (Jemperli).

Thus far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.  

The results were presented (Abstract 16) at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.

“In our study, the elimination of tumors after 6 months of therapy with PD-1 blockade enabled us to omit both chemoradiotherapy and surgery and to proceed with observation alone,” said the authors, led by Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center, New York.

About 5%-10% of patients with rectal cancer have tumors with dMMR.

“The implications for quality of life are substantial, especially among patients in whom standard treatment would affect child-bearing potential [and] given that the incidence of rectal cancer is rising among young adults of childbearing age, the use of PD-1 blockade to eliminate the need for chemoradiotherapy and surgery may confer a particular benefit in that age group,” the authors wrote.

The results of the current study are cause for “great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Dr. Hanna K. Sanoff, MD, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.
 

Single-agent dostarlimab

For the study, all patients were treated with single-agent dostarlimab every 3 weeks for 6 months.

Dostarlimab is already approved by the Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.

All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors noted that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.

For the study, investigators planned that patients who had a clinical complete response after completion of dostarlimab were to proceed to observation without undergoing either chemoradiotherapy or surgery, while those who did not have a complete response were to have received these standard treatments.

As it turned out, all 12 patients achieved a complete response and have been followed by observation alone. The median follow-up from time of enrollment to data cutoff for the 12 patients was 12 months.

“Therapeutic responses were rapid,” the authors noted, “with resolution of symptoms within 8 weeks after initiation of dostarlimab in 81% of the patients.”

To date, four patients have had 1 year of sustained clinical complete response after completion of the anti-PD-1 course.

In addition to the 12 patients documented in the study, another four patients have received at least one dose of dostarlimab and continue to receive treatment.

Adverse events occurred in most patients but none were grade 3 or higher. The most common grade 1 or 2 adverse events were rash or dermatitis, pruritus, fatigue, nausea and, in one patient, thyroid-function abnormalities.

The authors speculated that in addition to the extremely high tumor mutational burden associated with mismatch-repair deficiency, a tumor cell–extrinsic factor such as the gut microbiome may be driving the exceptionally good response to PD-1 blockade seen in this patient population.
 

Editorial commentary

In the editorial, Dr. Sanoff emphasized that the approach remains experimental and should not replace current curative treatment. She noted that cancer recurrences have been seen in other studies using both chemotherapy and immunotherapy. 

For example, with chemotherapy and radiation, those patients who achieve a clinical complete response have a better prognosis compared with those who do not, but she cautioned that “cancer regrowth occurs in 20% to 30% of such patients when the cancer is managed nonoperatively.”

Dr. Sanoff noted that recurrences were seen when this approach of PD-1 inhibition has been used for metastatic colorectal cancer with dMMR. In the KEYNOTE-177 trial with pembrolizumab (Keytruda), only 55% of patients were reported to be alive without cancer progression at 12 months, and of the patients who initially had a strong response, only 70% had an ongoing response 3 years later.

“These recurrence dynamics may (or may not) differ between immunotherapy and chemoradiotherapy and between early and late-stage disease,” Dr. Sanoff said.

“In fact, very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” she added.

In addition, Dr. Sanoff warned that the decision not to pursue further treatment and to follow patients with observation alone requires very close monitoring.

The current study was conducted at a top U.S. cancer center, Memorial Sloan Kettering Cancer Center. The authors noted that the complete responses (after a minimum of 6 months of follow-up) were measured by the combination of rectal MRI, visual endoscopic inspection, and digital rectal examination.

The completeness of these responses was further supported by the absence of residual tumor on serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake on PET scans, the authors added.

In the editorial, Dr. Sanoff said that “safe nonoperative management [also] involves access to specialty care for direct intraluminal visualization and expertise in interpretation of rectal magnetic resonance imaging ... Such expertise is not available in all communities and without it, patients could miss the opportunity for curative resection if tumor regrowth occurred.”

The study was sponsored by the Simon and Eve Colin Foundation, GlaxoSmithKline, and Stand Up to Cancer, among others. 

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

Patients with locally advanced rectal cancer and tumors with deficient mismatch repair (dMMR) have shown a remarkable response to treatment with the programmed cell death-1 (PD-1) inhibitor dostarlimab (Jemperli).

Thus far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.  

The results were presented (Abstract 16) at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.

“In our study, the elimination of tumors after 6 months of therapy with PD-1 blockade enabled us to omit both chemoradiotherapy and surgery and to proceed with observation alone,” said the authors, led by Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center, New York.

About 5%-10% of patients with rectal cancer have tumors with dMMR.

“The implications for quality of life are substantial, especially among patients in whom standard treatment would affect child-bearing potential [and] given that the incidence of rectal cancer is rising among young adults of childbearing age, the use of PD-1 blockade to eliminate the need for chemoradiotherapy and surgery may confer a particular benefit in that age group,” the authors wrote.

The results of the current study are cause for “great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Dr. Hanna K. Sanoff, MD, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.
 

Single-agent dostarlimab

For the study, all patients were treated with single-agent dostarlimab every 3 weeks for 6 months.

Dostarlimab is already approved by the Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.

All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors noted that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.

For the study, investigators planned that patients who had a clinical complete response after completion of dostarlimab were to proceed to observation without undergoing either chemoradiotherapy or surgery, while those who did not have a complete response were to have received these standard treatments.

As it turned out, all 12 patients achieved a complete response and have been followed by observation alone. The median follow-up from time of enrollment to data cutoff for the 12 patients was 12 months.

“Therapeutic responses were rapid,” the authors noted, “with resolution of symptoms within 8 weeks after initiation of dostarlimab in 81% of the patients.”

To date, four patients have had 1 year of sustained clinical complete response after completion of the anti-PD-1 course.

In addition to the 12 patients documented in the study, another four patients have received at least one dose of dostarlimab and continue to receive treatment.

Adverse events occurred in most patients but none were grade 3 or higher. The most common grade 1 or 2 adverse events were rash or dermatitis, pruritus, fatigue, nausea and, in one patient, thyroid-function abnormalities.

The authors speculated that in addition to the extremely high tumor mutational burden associated with mismatch-repair deficiency, a tumor cell–extrinsic factor such as the gut microbiome may be driving the exceptionally good response to PD-1 blockade seen in this patient population.
 

Editorial commentary

In the editorial, Dr. Sanoff emphasized that the approach remains experimental and should not replace current curative treatment. She noted that cancer recurrences have been seen in other studies using both chemotherapy and immunotherapy. 

For example, with chemotherapy and radiation, those patients who achieve a clinical complete response have a better prognosis compared with those who do not, but she cautioned that “cancer regrowth occurs in 20% to 30% of such patients when the cancer is managed nonoperatively.”

Dr. Sanoff noted that recurrences were seen when this approach of PD-1 inhibition has been used for metastatic colorectal cancer with dMMR. In the KEYNOTE-177 trial with pembrolizumab (Keytruda), only 55% of patients were reported to be alive without cancer progression at 12 months, and of the patients who initially had a strong response, only 70% had an ongoing response 3 years later.

“These recurrence dynamics may (or may not) differ between immunotherapy and chemoradiotherapy and between early and late-stage disease,” Dr. Sanoff said.

“In fact, very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” she added.

In addition, Dr. Sanoff warned that the decision not to pursue further treatment and to follow patients with observation alone requires very close monitoring.

The current study was conducted at a top U.S. cancer center, Memorial Sloan Kettering Cancer Center. The authors noted that the complete responses (after a minimum of 6 months of follow-up) were measured by the combination of rectal MRI, visual endoscopic inspection, and digital rectal examination.

The completeness of these responses was further supported by the absence of residual tumor on serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake on PET scans, the authors added.

In the editorial, Dr. Sanoff said that “safe nonoperative management [also] involves access to specialty care for direct intraluminal visualization and expertise in interpretation of rectal magnetic resonance imaging ... Such expertise is not available in all communities and without it, patients could miss the opportunity for curative resection if tumor regrowth occurred.”

The study was sponsored by the Simon and Eve Colin Foundation, GlaxoSmithKline, and Stand Up to Cancer, among others. 

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

Patients with locally advanced rectal cancer and tumors with deficient mismatch repair (dMMR) have shown a remarkable response to treatment with the programmed cell death-1 (PD-1) inhibitor dostarlimab (Jemperli).

Thus far, the study has involved only 12 patients, but all of them have had a clinical complete response to treatment. They continue to show no signs of cancer (during follow-up ranging from 6 to 25 months) and have not undergone surgery or had radiation and chemotherapy, which are the standard treatment approaches.  

The results were presented (Abstract 16) at the American Society of Clinical Oncology annual meeting and simultaneously published in the New England Journal of Medicine.

“In our study, the elimination of tumors after 6 months of therapy with PD-1 blockade enabled us to omit both chemoradiotherapy and surgery and to proceed with observation alone,” said the authors, led by Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center, New York.

About 5%-10% of patients with rectal cancer have tumors with dMMR.

“The implications for quality of life are substantial, especially among patients in whom standard treatment would affect child-bearing potential [and] given that the incidence of rectal cancer is rising among young adults of childbearing age, the use of PD-1 blockade to eliminate the need for chemoradiotherapy and surgery may confer a particular benefit in that age group,” the authors wrote.

The results of the current study are cause for “great optimism, but such an approach cannot yet supplant our current curative treatment approach,” Dr. Hanna K. Sanoff, MD, University of North Carolina at Chapel Hill, wrote in an accompanying editorial.
 

Single-agent dostarlimab

For the study, all patients were treated with single-agent dostarlimab every 3 weeks for 6 months.

Dostarlimab is already approved by the Food and Drug Administration for use in the treatment of recurrent or advanced endometrial cancer with dMMR. Rectal cancer is an off-label use.

All patients had mismatch repair-deficient stage 2 or 3 rectal adenocarcinoma. The authors noted that these tumors respond poorly to standard chemotherapy regimens, including neoadjuvant chemotherapy. The median age of enrolled patients was 54 years and 62% were women.

For the study, investigators planned that patients who had a clinical complete response after completion of dostarlimab were to proceed to observation without undergoing either chemoradiotherapy or surgery, while those who did not have a complete response were to have received these standard treatments.

As it turned out, all 12 patients achieved a complete response and have been followed by observation alone. The median follow-up from time of enrollment to data cutoff for the 12 patients was 12 months.

“Therapeutic responses were rapid,” the authors noted, “with resolution of symptoms within 8 weeks after initiation of dostarlimab in 81% of the patients.”

To date, four patients have had 1 year of sustained clinical complete response after completion of the anti-PD-1 course.

In addition to the 12 patients documented in the study, another four patients have received at least one dose of dostarlimab and continue to receive treatment.

Adverse events occurred in most patients but none were grade 3 or higher. The most common grade 1 or 2 adverse events were rash or dermatitis, pruritus, fatigue, nausea and, in one patient, thyroid-function abnormalities.

The authors speculated that in addition to the extremely high tumor mutational burden associated with mismatch-repair deficiency, a tumor cell–extrinsic factor such as the gut microbiome may be driving the exceptionally good response to PD-1 blockade seen in this patient population.
 

Editorial commentary

In the editorial, Dr. Sanoff emphasized that the approach remains experimental and should not replace current curative treatment. She noted that cancer recurrences have been seen in other studies using both chemotherapy and immunotherapy. 

For example, with chemotherapy and radiation, those patients who achieve a clinical complete response have a better prognosis compared with those who do not, but she cautioned that “cancer regrowth occurs in 20% to 30% of such patients when the cancer is managed nonoperatively.”

Dr. Sanoff noted that recurrences were seen when this approach of PD-1 inhibition has been used for metastatic colorectal cancer with dMMR. In the KEYNOTE-177 trial with pembrolizumab (Keytruda), only 55% of patients were reported to be alive without cancer progression at 12 months, and of the patients who initially had a strong response, only 70% had an ongoing response 3 years later.

“These recurrence dynamics may (or may not) differ between immunotherapy and chemoradiotherapy and between early and late-stage disease,” Dr. Sanoff said.

“In fact, very little is known about the duration of time needed to find out whether a clinical complete response to dostarlimab equates to cure,” she added.

In addition, Dr. Sanoff warned that the decision not to pursue further treatment and to follow patients with observation alone requires very close monitoring.

The current study was conducted at a top U.S. cancer center, Memorial Sloan Kettering Cancer Center. The authors noted that the complete responses (after a minimum of 6 months of follow-up) were measured by the combination of rectal MRI, visual endoscopic inspection, and digital rectal examination.

The completeness of these responses was further supported by the absence of residual tumor on serial endoscopic biopsies and the resolution of 18F-fluorodeoxyglucose uptake on PET scans, the authors added.

In the editorial, Dr. Sanoff said that “safe nonoperative management [also] involves access to specialty care for direct intraluminal visualization and expertise in interpretation of rectal magnetic resonance imaging ... Such expertise is not available in all communities and without it, patients could miss the opportunity for curative resection if tumor regrowth occurred.”

The study was sponsored by the Simon and Eve Colin Foundation, GlaxoSmithKline, and Stand Up to Cancer, among others. 

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

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

A new study shows that being overweight may offer some women undergoing treatment for breast cancer protection against neutropenia – a potentially deadly outcome that can occur as a result of chemotherapy treatment.

The study was presented at the annual meeting of the American Society of Clinical Oncology.

It is known that body mass index can affect breast cancer risk and prognosis, but it is not known if BMI can affect how well endocrine therapy works in a given patient. In the PALLAS clinical trial, Georg Pfeiler, MD, Medical University of Vienna, and colleagues, conducted an analysis of 5,698 patients with early hormone receptor–positive breast cancer receiving endocrine therapy with or without palbociclib. Dr. Pfeiler found that women who are overweight or obese had significantly less frequent and less severe cases of neutropenia. With fewer or less severe cases of neutropenia, there were also fewer interruptions in palbociclib treatment.

“One explanation for the lower discontinuation rates may be that the distributional volume of the drug is higher in overweight and obese patients leading to lower serum drug concentrations. It could also be influenced by differences in pharmacokinetics with respect to hyperinsulinemia,” said Dr. Pfeiler, who leads the Oncological Breast Outpatient Clinic and Bone Health Outpatient Clinic at the Medical University of Vienna.

The PALLAS trial compared the combination of palbociclib and adjuvant endocrine therapy with endocrine therapy alone in 5,698 women with early breast cancer. Patients were categorized according to BMI as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9), overweight (BMI, 25-29.9), and obese (> 30). The investigators analyzed differences in adverse events, time to early discontinuation of palbociclib, and in time to invasive disease-free survival.

At baseline, of 5,698 patients, 68 (1.2%) were underweight, 2,082 (36.5%) were of normal weight, 1,818 (31.9%) were overweight, and, 1,730 (30.4%) were obese. In patients treated with palbociclib, neutropenia was the primary toxicity leading to treatment discontinuation with rates of 21.1% in normal-weight patients, 14.0% of overweight patients, and 5.9% of obese patients, respectively.

Significantly different rates of all-grade neutropenia were observed in normal weight, overweight, and obese participants with regard to total (88.5%, 85.7% and 74.7%), as well as grade 3 (64.1%, 62.0% and 43.9%) and grade 4 neutropenia (7.0%, 3.6% and 2.0%), respectively. The lower frequency and severity of neutropenia observed in overweight and obese patients was associated with a significantly lower treatment discontinuation rate over time when compared with normal-weight patients (overweight vs. normal weight: HR, 0.73; 95% CI 0.63-0.84; P < .0001, and obese vs. normal weight: HR, 0.65; 95% CI, 0.56-0.75; P < .0001). There was, however, despite these observations, no statistically significant improvement in invasive disease survival with the addition of palbociclib to endocrine therapy in any weight category (normal weight: HR, 0.84; 95% CI 0.63-1.12; overweight: HR, 1.10; 95% CI 0.82-1.49; and obese: HR, 0.95; 95% CI, 0.69-1.30).

“This is an early analysis, and should be interpreted with caution, especially with regard to disease outcomes. The findings may reduce concerns over hematologic side effects in the overweight and obese. In the future there may be an important impact if it turns out after longer-term follow-up that palbociclib has been underdosed in the overweight and obese. We may need BMI-adapted dose management,” said Dr. Pfeiler, who is currently working on a longer-term follow-up study of the PALLAS group.

The analysis found no significant correlation between weight and occurrence of invasive disease events.

Dr. Pfeiler disclosed honoraria and grants from Pfizer. The study was funded by Alliance Foundation Trials.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

When a patient first presents to a doctor with signs and symptoms of having breast cancer that has metastasized to other parts of the body, the prospects of long-term survival are dim. But now, a new study presented at the annual meeting of the American Society of Clinical Oncology suggests that women with metastatic HER2+ breast cancer are generally living longer, compared with women treated in previous years.

Between 2010 and 2018, the overall survival for 5,576 women (99% women) with HER2+ metastatic breast cancer enrolled in this study improved 5.6% each year of the study. The study also showed a 6.4% improvement in breast cancer–specific death rates year over year.

“These highlights coincide with significant therapeutic advances for HER2+ metastatic breast cancer over the past decade. We need to continue our research efforts to identify better treatments for our patients so we can continue to improve the prognosis of these patients,” said study author Jose Pablo Leone, MD, a medical oncologist with Dana-Farber Cancer Institute, Boston.

The study, which is based on an evaluation of data from the Surveillance, Epidemiology and End Results database, found factors associated with shorter survival included older age, Black race, lower income, and the presence of visceral or brain metastases. Long-term survival of more than 5 years was associated with younger age, White race, and higher income, but also having fewer metastatic sites and estrogen receptor (ER)/progesterone receptor (PR) positivity.

“We also found specific factors that were only associated with shorter overall survival, such as the presence of metastases in the brain, liver, or lung. The lack of metastasis in these sites was not associated with longer overall survival. In contrast, a lower number of metastatic sites, regardless of the location of those sites were associated with longer overall survival but not short-term survival,” Dr. Leone said.

A total of 63.3% of patients in the study survived less than 2 years while 37.8% lived 5 years or more, and 26.8% lived longer than 8 years. Factors associated with less than 2 years in overall survival were older age (odds ratio, 3.76), Black race (OR 1.5), nonductal nonlobular (OR, 4.64), brain metastases (OR, 2.95), liver metastases (OR, 1.98), lung metastases (OR, 1.56), ER/PR negativity (OR, 1.74), and lower income (OR, 1.62). Factors associated with longer survival of 5 years or more included younger age (OR, 2.85), White race (OR, 1.7), fewer metastatic organ sites (OR, 2.6), ER/PR positivity (OR, 1.27), and higher income (OR, 3.31).

Dr. Leone said that, while involvement of specific visceral sites (brain, liver, lung) was associated with shorter overall survival, the odds of living longer than 5 years was not associated with those sites. In contrast, the number of sites was associated with longer overall survival, but not shorter overall survival regardless of location. “While fewer number of metastatic sites were associated with higher odds of overall survival greater than 5 years, the number of metastatic sites was not associated with the odds of overall survival of being less than 2 years,” he said.

A limitation of the study included the retrospective nature of the study. “Treatment data are unavailable, so we cannot quantify the impact of various treatments on the odds of survival,” Dr. Leone said.

This study was not funded.

A suspicion from retrospective data has now been confirmed by a prospective clinical trial: Adding panitumumab (Vectibix) to standard chemotherapy in left-sided RAS wild-type metastatic colorectal cancer (mCRC) is more effective than adding bevacizumab (Avastin).

Patients treated with panitumumab alongside chemotherapy saw a 16% improvement in overall survival versus those given bevacizumab after a median follow-up of over 5 years.

The overall survival benefit rose to 18% in those with left-sided tumors.

However, there was no difference in overall survival between the two treatment groups in the small subgroup of patients with right-sided primary tumors.

These findings come from the PARADIGM trial conducted in Japan.

The results were presented during a plenary session at the annual meeting of the American Society of Clinical Oncology.

“If gene testing shows that a tumor is RAS wild-type, the choice of initial treatment with panitumumab plus mFOLFOX6 chemotherapy is superior ... for those people with left-sided tumors,” said lead researcher Takayuki Yoshino, MD, PhD, department of gastrointestinal oncology, National Cancer Center Hospital East, Chiba, Japan, in an ASCO press release.

“It has long been believed that the sequence of metastatic colorectal cancer treatment does not matter as long as patients had access to the drugs at some point, which has now been disproven,” he noted.

Dr. Yoshino added in a press conference about the trial that the results establish “a standard first-line combination regimen for patients with RAS wild-type, left-sided mCRC.”

This is the “longest survival ever reported in a first-line unresectable metastatic colorectal cancer prospective phase 3 trial,” commented Cathy Eng, MD, ASCO Expert in gastrointestinal cancers.

The findings “emphasize the importance of taking into account sidedness, as well as including comprehensive biomarker testing,” she said.

Dr. Eng underlined that this is especially the case for RAS gene status testing, “which is critical for all colorectal cancer patients at the time of diagnosis of metastatic disease.”

These results are of particular relevance in the United States, where the choice between an anti-EGFR or anti-VEGF antibody for the treatment of mCRC has been an area of “controversy” because of the lack of supporting data.

Panitumumab is a human monoclonal antibody that targets EGFR. It was approved in 2006 for use in mCRC by the U.S. Food and Drug Administration and also approved in 2014 for use in combination with FOLFOX for the first-line treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, having previously been shown to be equally effective as cetuximab (another EGFR inhibitor) in this population.

In contrast, bevacizumab is a monoclonal antibody that targets the VEGF receptor. It was approved by the FDA for use in mCRC in 2004 in combination with intravenous 5-fluorouracil–based chemotherapy.

Dr. Yoshino explained that around 36% of patients with CRC have metastatic tumors at diagnosis and that adding an anti-EGFR or anti-VEGF antibody to chemotherapy improves overall survival in these patients by up to 30 months.

There has been “accumulating” evidence from retrospective studies suggesting that patients with RAS wild-type mCRC whose primary tumor is on the left side, which accounts for approximately 35% of mCRC cases, have a longer survival benefit with an anti-EGFR antibody, he commented.

Despite this, both antibody types continue to be used in these patients, he added.

PARADIGM was the first prospective trial to compare the two antibody types. Patients were randomized to receive either panitumumab or bevacizumab plus the combination chemotherapy regimen modified FOLFOX6 (mFOLFOX6).

The trial involved 823 Japanese patients with previously untreated wild-type mCRC with unresectable disease. Most patients had left-sided primary tumors (312 of 400 patients in the panitumumab group, and 292 of 402 patients in the bevacizumab group).  

After a median follow-up of 61 months, panitumumab was associated with a significant improvement in overall survival in the overall study population, at a hazard ratio of 0.84 (P = .030, with the boundary of significance set at P < .05).

In addition, panitumumab was associated with a significant improvement in overall survival in the large subgroup of patients with left-sided primary tumors, at 37.9 versus 34.3 months, or a hazard ratio of 0.82 (P = .031).

However, there was no significant difference in overall survival between the two treatment groups in the smaller subgroup of patients with right-sided tumors, at a hazard ratio of 1.09.

Median progression-free survival was no different between the panitumumab and bevacizumab groups, at 13.7 versus 13.2 months in patients with a left-sided tumor and 12.9 versus 12.0 months in the overall cohort.

There was, however, a difference in response rates in left-sided patients between those receiving the two antibodies, at 80.2% with panitumumab versus 68.6% with bevacizumab, and in curative resection rates, at 18.3% and 11.6%, respectively.

These results demonstrate the “superiority of first-line panitumumab versus bevacizumab in combination with mFOLFOX6 in the left-sided and overall populations,” Dr. Yoshino concluded.

He also highlighted that the team has undertaken a large-scale biomarker analysis of pre- and posttreatment plasma and tissue samples from patients in the PARADIGM study to identify potential biomarkers of treatment response.

At the plenary session, discussant for this abstract Chiara Cremolini, MD, PhD, professor of medical oncology, Pisa (Italy) University Hospital, commented that “location matters” when it comes to mCRC tumors.

Dr. Cremolini pointed out that the separation of the survival curves at 28 months suggests that the 40% of patients with left-sided tumors who survived only up until that time point receive an equal benefit from panitumumab and bevacizumab.

In contrast, the remainder who survived for longer showed better outcomes with panitumumab.

Overall, she said, in her opinion and based on the findings from other studies, the current results support the use of panitumumab plus mFOLFOX6 as first-line therapy in patients with microsatellite stable RAS wild-type and with BRAF wild-type left-sided mCRC.

Dr. Cremolini emphasized that patients should be warned that, if they opt for doublet chemotherapy plus bevacizumab, they could face a median 3.6-month loss in overall survival, as well as poorer treatment activity.

However, patients with high microsatellite instability should receive immunotherapy up front, she added, while those with BRAF mutations should be given FOLFOX upfront plus bevacizumab, followed by encorafenib plus cetuximab in the case of progression.

Dr. Cremolini ended by noting that there has, as yet, been no prospective comparison of doublet chemotherapy plus an anti-EGFR antibody with triplet chemotherapy plus bevacizumab in this population.

The study was funded by Takeda. Dr. Yoshino has reported relationships with Bayer Yakuhin, Chugai Pharmaceutical, Merck, and MSD. Dr. Eng has reported relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer.

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

A suspicion from retrospective data has now been confirmed by a prospective clinical trial: Adding panitumumab (Vectibix) to standard chemotherapy in left-sided RAS wild-type metastatic colorectal cancer (mCRC) is more effective than adding bevacizumab (Avastin).

Patients treated with panitumumab alongside chemotherapy saw a 16% improvement in overall survival versus those given bevacizumab after a median follow-up of over 5 years.

The overall survival benefit rose to 18% in those with left-sided tumors.

However, there was no difference in overall survival between the two treatment groups in the small subgroup of patients with right-sided primary tumors.

These findings come from the PARADIGM trial conducted in Japan.

The results were presented during a plenary session at the annual meeting of the American Society of Clinical Oncology.

“If gene testing shows that a tumor is RAS wild-type, the choice of initial treatment with panitumumab plus mFOLFOX6 chemotherapy is superior ... for those people with left-sided tumors,” said lead researcher Takayuki Yoshino, MD, PhD, department of gastrointestinal oncology, National Cancer Center Hospital East, Chiba, Japan, in an ASCO press release.

“It has long been believed that the sequence of metastatic colorectal cancer treatment does not matter as long as patients had access to the drugs at some point, which has now been disproven,” he noted.

Dr. Yoshino added in a press conference about the trial that the results establish “a standard first-line combination regimen for patients with RAS wild-type, left-sided mCRC.”

This is the “longest survival ever reported in a first-line unresectable metastatic colorectal cancer prospective phase 3 trial,” commented Cathy Eng, MD, ASCO Expert in gastrointestinal cancers.

The findings “emphasize the importance of taking into account sidedness, as well as including comprehensive biomarker testing,” she said.

Dr. Eng underlined that this is especially the case for RAS gene status testing, “which is critical for all colorectal cancer patients at the time of diagnosis of metastatic disease.”

These results are of particular relevance in the United States, where the choice between an anti-EGFR or anti-VEGF antibody for the treatment of mCRC has been an area of “controversy” because of the lack of supporting data.

Panitumumab is a human monoclonal antibody that targets EGFR. It was approved in 2006 for use in mCRC by the U.S. Food and Drug Administration and also approved in 2014 for use in combination with FOLFOX for the first-line treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, having previously been shown to be equally effective as cetuximab (another EGFR inhibitor) in this population.

In contrast, bevacizumab is a monoclonal antibody that targets the VEGF receptor. It was approved by the FDA for use in mCRC in 2004 in combination with intravenous 5-fluorouracil–based chemotherapy.

Dr. Yoshino explained that around 36% of patients with CRC have metastatic tumors at diagnosis and that adding an anti-EGFR or anti-VEGF antibody to chemotherapy improves overall survival in these patients by up to 30 months.

There has been “accumulating” evidence from retrospective studies suggesting that patients with RAS wild-type mCRC whose primary tumor is on the left side, which accounts for approximately 35% of mCRC cases, have a longer survival benefit with an anti-EGFR antibody, he commented.

Despite this, both antibody types continue to be used in these patients, he added.

PARADIGM was the first prospective trial to compare the two antibody types. Patients were randomized to receive either panitumumab or bevacizumab plus the combination chemotherapy regimen modified FOLFOX6 (mFOLFOX6).

The trial involved 823 Japanese patients with previously untreated wild-type mCRC with unresectable disease. Most patients had left-sided primary tumors (312 of 400 patients in the panitumumab group, and 292 of 402 patients in the bevacizumab group).  

After a median follow-up of 61 months, panitumumab was associated with a significant improvement in overall survival in the overall study population, at a hazard ratio of 0.84 (P = .030, with the boundary of significance set at P < .05).

In addition, panitumumab was associated with a significant improvement in overall survival in the large subgroup of patients with left-sided primary tumors, at 37.9 versus 34.3 months, or a hazard ratio of 0.82 (P = .031).

However, there was no significant difference in overall survival between the two treatment groups in the smaller subgroup of patients with right-sided tumors, at a hazard ratio of 1.09.

Median progression-free survival was no different between the panitumumab and bevacizumab groups, at 13.7 versus 13.2 months in patients with a left-sided tumor and 12.9 versus 12.0 months in the overall cohort.

There was, however, a difference in response rates in left-sided patients between those receiving the two antibodies, at 80.2% with panitumumab versus 68.6% with bevacizumab, and in curative resection rates, at 18.3% and 11.6%, respectively.

These results demonstrate the “superiority of first-line panitumumab versus bevacizumab in combination with mFOLFOX6 in the left-sided and overall populations,” Dr. Yoshino concluded.

He also highlighted that the team has undertaken a large-scale biomarker analysis of pre- and posttreatment plasma and tissue samples from patients in the PARADIGM study to identify potential biomarkers of treatment response.

At the plenary session, discussant for this abstract Chiara Cremolini, MD, PhD, professor of medical oncology, Pisa (Italy) University Hospital, commented that “location matters” when it comes to mCRC tumors.

Dr. Cremolini pointed out that the separation of the survival curves at 28 months suggests that the 40% of patients with left-sided tumors who survived only up until that time point receive an equal benefit from panitumumab and bevacizumab.

In contrast, the remainder who survived for longer showed better outcomes with panitumumab.

Overall, she said, in her opinion and based on the findings from other studies, the current results support the use of panitumumab plus mFOLFOX6 as first-line therapy in patients with microsatellite stable RAS wild-type and with BRAF wild-type left-sided mCRC.

Dr. Cremolini emphasized that patients should be warned that, if they opt for doublet chemotherapy plus bevacizumab, they could face a median 3.6-month loss in overall survival, as well as poorer treatment activity.

However, patients with high microsatellite instability should receive immunotherapy up front, she added, while those with BRAF mutations should be given FOLFOX upfront plus bevacizumab, followed by encorafenib plus cetuximab in the case of progression.

Dr. Cremolini ended by noting that there has, as yet, been no prospective comparison of doublet chemotherapy plus an anti-EGFR antibody with triplet chemotherapy plus bevacizumab in this population.

The study was funded by Takeda. Dr. Yoshino has reported relationships with Bayer Yakuhin, Chugai Pharmaceutical, Merck, and MSD. Dr. Eng has reported relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer.

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

A suspicion from retrospective data has now been confirmed by a prospective clinical trial: Adding panitumumab (Vectibix) to standard chemotherapy in left-sided RAS wild-type metastatic colorectal cancer (mCRC) is more effective than adding bevacizumab (Avastin).

Patients treated with panitumumab alongside chemotherapy saw a 16% improvement in overall survival versus those given bevacizumab after a median follow-up of over 5 years.

The overall survival benefit rose to 18% in those with left-sided tumors.

However, there was no difference in overall survival between the two treatment groups in the small subgroup of patients with right-sided primary tumors.

These findings come from the PARADIGM trial conducted in Japan.

The results were presented during a plenary session at the annual meeting of the American Society of Clinical Oncology.

“If gene testing shows that a tumor is RAS wild-type, the choice of initial treatment with panitumumab plus mFOLFOX6 chemotherapy is superior ... for those people with left-sided tumors,” said lead researcher Takayuki Yoshino, MD, PhD, department of gastrointestinal oncology, National Cancer Center Hospital East, Chiba, Japan, in an ASCO press release.

“It has long been believed that the sequence of metastatic colorectal cancer treatment does not matter as long as patients had access to the drugs at some point, which has now been disproven,” he noted.

Dr. Yoshino added in a press conference about the trial that the results establish “a standard first-line combination regimen for patients with RAS wild-type, left-sided mCRC.”

This is the “longest survival ever reported in a first-line unresectable metastatic colorectal cancer prospective phase 3 trial,” commented Cathy Eng, MD, ASCO Expert in gastrointestinal cancers.

The findings “emphasize the importance of taking into account sidedness, as well as including comprehensive biomarker testing,” she said.

Dr. Eng underlined that this is especially the case for RAS gene status testing, “which is critical for all colorectal cancer patients at the time of diagnosis of metastatic disease.”

These results are of particular relevance in the United States, where the choice between an anti-EGFR or anti-VEGF antibody for the treatment of mCRC has been an area of “controversy” because of the lack of supporting data.

Panitumumab is a human monoclonal antibody that targets EGFR. It was approved in 2006 for use in mCRC by the U.S. Food and Drug Administration and also approved in 2014 for use in combination with FOLFOX for the first-line treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) mCRC, having previously been shown to be equally effective as cetuximab (another EGFR inhibitor) in this population.

In contrast, bevacizumab is a monoclonal antibody that targets the VEGF receptor. It was approved by the FDA for use in mCRC in 2004 in combination with intravenous 5-fluorouracil–based chemotherapy.

Dr. Yoshino explained that around 36% of patients with CRC have metastatic tumors at diagnosis and that adding an anti-EGFR or anti-VEGF antibody to chemotherapy improves overall survival in these patients by up to 30 months.

There has been “accumulating” evidence from retrospective studies suggesting that patients with RAS wild-type mCRC whose primary tumor is on the left side, which accounts for approximately 35% of mCRC cases, have a longer survival benefit with an anti-EGFR antibody, he commented.

Despite this, both antibody types continue to be used in these patients, he added.

PARADIGM was the first prospective trial to compare the two antibody types. Patients were randomized to receive either panitumumab or bevacizumab plus the combination chemotherapy regimen modified FOLFOX6 (mFOLFOX6).

The trial involved 823 Japanese patients with previously untreated wild-type mCRC with unresectable disease. Most patients had left-sided primary tumors (312 of 400 patients in the panitumumab group, and 292 of 402 patients in the bevacizumab group).  

After a median follow-up of 61 months, panitumumab was associated with a significant improvement in overall survival in the overall study population, at a hazard ratio of 0.84 (P = .030, with the boundary of significance set at P < .05).

In addition, panitumumab was associated with a significant improvement in overall survival in the large subgroup of patients with left-sided primary tumors, at 37.9 versus 34.3 months, or a hazard ratio of 0.82 (P = .031).

However, there was no significant difference in overall survival between the two treatment groups in the smaller subgroup of patients with right-sided tumors, at a hazard ratio of 1.09.

Median progression-free survival was no different between the panitumumab and bevacizumab groups, at 13.7 versus 13.2 months in patients with a left-sided tumor and 12.9 versus 12.0 months in the overall cohort.

There was, however, a difference in response rates in left-sided patients between those receiving the two antibodies, at 80.2% with panitumumab versus 68.6% with bevacizumab, and in curative resection rates, at 18.3% and 11.6%, respectively.

These results demonstrate the “superiority of first-line panitumumab versus bevacizumab in combination with mFOLFOX6 in the left-sided and overall populations,” Dr. Yoshino concluded.

He also highlighted that the team has undertaken a large-scale biomarker analysis of pre- and posttreatment plasma and tissue samples from patients in the PARADIGM study to identify potential biomarkers of treatment response.

At the plenary session, discussant for this abstract Chiara Cremolini, MD, PhD, professor of medical oncology, Pisa (Italy) University Hospital, commented that “location matters” when it comes to mCRC tumors.

Dr. Cremolini pointed out that the separation of the survival curves at 28 months suggests that the 40% of patients with left-sided tumors who survived only up until that time point receive an equal benefit from panitumumab and bevacizumab.

In contrast, the remainder who survived for longer showed better outcomes with panitumumab.

Overall, she said, in her opinion and based on the findings from other studies, the current results support the use of panitumumab plus mFOLFOX6 as first-line therapy in patients with microsatellite stable RAS wild-type and with BRAF wild-type left-sided mCRC.

Dr. Cremolini emphasized that patients should be warned that, if they opt for doublet chemotherapy plus bevacizumab, they could face a median 3.6-month loss in overall survival, as well as poorer treatment activity.

However, patients with high microsatellite instability should receive immunotherapy up front, she added, while those with BRAF mutations should be given FOLFOX upfront plus bevacizumab, followed by encorafenib plus cetuximab in the case of progression.

Dr. Cremolini ended by noting that there has, as yet, been no prospective comparison of doublet chemotherapy plus an anti-EGFR antibody with triplet chemotherapy plus bevacizumab in this population.

The study was funded by Takeda. Dr. Yoshino has reported relationships with Bayer Yakuhin, Chugai Pharmaceutical, Merck, and MSD. Dr. Eng has reported relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer.

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

A cohort study has found increases in mortality rates among women with non-endometrioid uterine carcinoma, despite incident rates that have stabilized. After correction with hysterectomy, mortality risk was about doubled for Black women, compared with White women, and these results could not be explained by differences in cancer subtype or cancer stage at diagnosis. Non-endometroid uterine carcinoma represents 15%-20% of uterine cancers diagnosed and carries a worse prognosis.

“We do not know why non-endometrioid subtypes are disproportionately increasing among all women, nor do we understand why they are so much more common among non-Hispanic Black women. We need more research to identify risk factors and exposures more specifically associated with non-endometrioid cancers to better understand the strong increases in this subtype among all women and the particularly high rates and recent increases in non-Hispanic black women,” said lead author Megan Clarke, PhD, MHS, the study’s lead author and a cancer epidemiologist with the National Cancer Institute.

The study was published online in JAMA Oncology.

“Physicians should be aware that both incidence and mortality rates of non-endometrioid cancers are on the rise. Because these subtypes are rarer than endometrioid uterine cancers, physicians may be less familiar with diagnosing and treating these aggressive types of cancers. Increasing awareness among clinicians and patients regarding the signs and symptoms of uterine cancer (such as postmenopausal bleeding) and the differences in histologic subtypes among racial and ethnic groups may promote earlier diagnosis and timely referral to appropriate treatment,” Dr. Clarke said.

Previous studies based on death certificates found increased mortality, especially in Black women, but they were limited by an inability to link mortality to tumor characteristics. To address this, the researchers linked mortality data to records of 208,587 women diagnosed with uterine cancer between 2000 and 2017, drawn from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

Black women represented 9.7% of cases, but they suffered 17.7% of uterine cancer deaths. Overall, mortality from uterine corpus cancer increased by 1.8% per year (95% confidence interval, 1.5%-2.9%). Non-endometroid cancers increased at 2.7% per year (95% CI, 1.8%-3.6%), and this was higher in Asian (3.4%; 95% CI, 0.3%-6.6%), Black (3.5%; 95% CI, 2.2%-4.9%), Hispanic (6.7%; 95% CI, 1.9%-11.8%), and White women (1.5%; 95% CI, 0.6%-2.4%).

Mortality increased 1.8% per year overall for uterine cancer and 2.7% per year for non-endometrioid uterine cancer. There was no increase in mortality seen in endometrioid cancers.

“The concerning rise in deaths from non-endometrioid cancers warrants clinical attention. Our findings suggest that there may be several factors contributing to racial disparities in uterine cancer mortality. Higher mortality rates among non-Hispanic Black women are partly attributable to higher incidence of tumors with aggressive subtypes and advanced stages. However, non-Hispanic Black women in our study who were diagnosed with less aggressive subtypes and early-stage disease also had the highest mortality rates,” said Dr. Clarke.

That suggests that inequities of treatment and high-quality care may be at least partly to blame, since those factors are known to contribute to differences in uterine cancer outcomes. “Other factors including comorbidities, health care facility characteristics, treatment preferences and adherence, patient and provider communication, provider bias, discrimination and structural racism, and potential biologic differences in response to treatment need to be better understood in terms of how they influence racial disparities,” Dr. Clarke said.

Dr. Clarke reported no relevant disclosures.

A cohort study has found increases in mortality rates among women with non-endometrioid uterine carcinoma, despite incident rates that have stabilized. After correction with hysterectomy, mortality risk was about doubled for Black women, compared with White women, and these results could not be explained by differences in cancer subtype or cancer stage at diagnosis. Non-endometroid uterine carcinoma represents 15%-20% of uterine cancers diagnosed and carries a worse prognosis.

“We do not know why non-endometrioid subtypes are disproportionately increasing among all women, nor do we understand why they are so much more common among non-Hispanic Black women. We need more research to identify risk factors and exposures more specifically associated with non-endometrioid cancers to better understand the strong increases in this subtype among all women and the particularly high rates and recent increases in non-Hispanic black women,” said lead author Megan Clarke, PhD, MHS, the study’s lead author and a cancer epidemiologist with the National Cancer Institute.

The study was published online in JAMA Oncology.

“Physicians should be aware that both incidence and mortality rates of non-endometrioid cancers are on the rise. Because these subtypes are rarer than endometrioid uterine cancers, physicians may be less familiar with diagnosing and treating these aggressive types of cancers. Increasing awareness among clinicians and patients regarding the signs and symptoms of uterine cancer (such as postmenopausal bleeding) and the differences in histologic subtypes among racial and ethnic groups may promote earlier diagnosis and timely referral to appropriate treatment,” Dr. Clarke said.

Previous studies based on death certificates found increased mortality, especially in Black women, but they were limited by an inability to link mortality to tumor characteristics. To address this, the researchers linked mortality data to records of 208,587 women diagnosed with uterine cancer between 2000 and 2017, drawn from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

Black women represented 9.7% of cases, but they suffered 17.7% of uterine cancer deaths. Overall, mortality from uterine corpus cancer increased by 1.8% per year (95% confidence interval, 1.5%-2.9%). Non-endometroid cancers increased at 2.7% per year (95% CI, 1.8%-3.6%), and this was higher in Asian (3.4%; 95% CI, 0.3%-6.6%), Black (3.5%; 95% CI, 2.2%-4.9%), Hispanic (6.7%; 95% CI, 1.9%-11.8%), and White women (1.5%; 95% CI, 0.6%-2.4%).

Mortality increased 1.8% per year overall for uterine cancer and 2.7% per year for non-endometrioid uterine cancer. There was no increase in mortality seen in endometrioid cancers.

“The concerning rise in deaths from non-endometrioid cancers warrants clinical attention. Our findings suggest that there may be several factors contributing to racial disparities in uterine cancer mortality. Higher mortality rates among non-Hispanic Black women are partly attributable to higher incidence of tumors with aggressive subtypes and advanced stages. However, non-Hispanic Black women in our study who were diagnosed with less aggressive subtypes and early-stage disease also had the highest mortality rates,” said Dr. Clarke.

That suggests that inequities of treatment and high-quality care may be at least partly to blame, since those factors are known to contribute to differences in uterine cancer outcomes. “Other factors including comorbidities, health care facility characteristics, treatment preferences and adherence, patient and provider communication, provider bias, discrimination and structural racism, and potential biologic differences in response to treatment need to be better understood in terms of how they influence racial disparities,” Dr. Clarke said.

Dr. Clarke reported no relevant disclosures.

A cohort study has found increases in mortality rates among women with non-endometrioid uterine carcinoma, despite incident rates that have stabilized. After correction with hysterectomy, mortality risk was about doubled for Black women, compared with White women, and these results could not be explained by differences in cancer subtype or cancer stage at diagnosis. Non-endometroid uterine carcinoma represents 15%-20% of uterine cancers diagnosed and carries a worse prognosis.

“We do not know why non-endometrioid subtypes are disproportionately increasing among all women, nor do we understand why they are so much more common among non-Hispanic Black women. We need more research to identify risk factors and exposures more specifically associated with non-endometrioid cancers to better understand the strong increases in this subtype among all women and the particularly high rates and recent increases in non-Hispanic black women,” said lead author Megan Clarke, PhD, MHS, the study’s lead author and a cancer epidemiologist with the National Cancer Institute.

The study was published online in JAMA Oncology.

“Physicians should be aware that both incidence and mortality rates of non-endometrioid cancers are on the rise. Because these subtypes are rarer than endometrioid uterine cancers, physicians may be less familiar with diagnosing and treating these aggressive types of cancers. Increasing awareness among clinicians and patients regarding the signs and symptoms of uterine cancer (such as postmenopausal bleeding) and the differences in histologic subtypes among racial and ethnic groups may promote earlier diagnosis and timely referral to appropriate treatment,” Dr. Clarke said.

Previous studies based on death certificates found increased mortality, especially in Black women, but they were limited by an inability to link mortality to tumor characteristics. To address this, the researchers linked mortality data to records of 208,587 women diagnosed with uterine cancer between 2000 and 2017, drawn from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program.

Black women represented 9.7% of cases, but they suffered 17.7% of uterine cancer deaths. Overall, mortality from uterine corpus cancer increased by 1.8% per year (95% confidence interval, 1.5%-2.9%). Non-endometroid cancers increased at 2.7% per year (95% CI, 1.8%-3.6%), and this was higher in Asian (3.4%; 95% CI, 0.3%-6.6%), Black (3.5%; 95% CI, 2.2%-4.9%), Hispanic (6.7%; 95% CI, 1.9%-11.8%), and White women (1.5%; 95% CI, 0.6%-2.4%).

Mortality increased 1.8% per year overall for uterine cancer and 2.7% per year for non-endometrioid uterine cancer. There was no increase in mortality seen in endometrioid cancers.

“The concerning rise in deaths from non-endometrioid cancers warrants clinical attention. Our findings suggest that there may be several factors contributing to racial disparities in uterine cancer mortality. Higher mortality rates among non-Hispanic Black women are partly attributable to higher incidence of tumors with aggressive subtypes and advanced stages. However, non-Hispanic Black women in our study who were diagnosed with less aggressive subtypes and early-stage disease also had the highest mortality rates,” said Dr. Clarke.

That suggests that inequities of treatment and high-quality care may be at least partly to blame, since those factors are known to contribute to differences in uterine cancer outcomes. “Other factors including comorbidities, health care facility characteristics, treatment preferences and adherence, patient and provider communication, provider bias, discrimination and structural racism, and potential biologic differences in response to treatment need to be better understood in terms of how they influence racial disparities,” Dr. Clarke said.

Dr. Clarke reported no relevant disclosures.

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

In the largest investigation into the issue to date, metformin did not improve survival of patients with high-risk, operable breast cancer when added to standard adjuvant treatments.

Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.

These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.

Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.

These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.

The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.

However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.

The study was published online in JAMA.

Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.

Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.

Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).

Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).

However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).

The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.

This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.

Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).

The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.

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

Some smokers might not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations to DNA that would turn cells malignant and make them grow into tumors, the researchers say.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was hard for them to identify the mutations in healthy cells that might help predict future cancer risk, Jan Vijg, PhD, a senior author of the study and researcher at the University School of Medicine, Shanghai, China, said in a statement.

His team used a process called single-cell whole genome sequencing to examine cells lining the lungs of 19 smokers and 14 nonsmokers ranging in age from their pre-teens to their mid-80s. The cells came from patients who had tissue samples collected from their lungs during diagnostic testing unrelated to cancer. The scientists reported their findings in Nature Genetics.

The researchers specifically looked at cells lining the lungs because these cells can survive for years and build up mutations over time that are linked to aging and smoking.

“Of all the lung’s cell types, these are among the most likely to become cancerous,” says Simon Spivack, MD, a senior author of the study and professor at the Albert Einstein College of Medicine, New York.

Smokers had far more gene mutations that can cause lung cancer than nonsmokers, the analysis found.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” says Dr. Spivack. “This is likely one reason why so few nonsmokers get lung cancer, while 10 to 20 percent of lifelong smokers do.”

Among the smokers, people had smoked a maximum of 116 pack-years. A pack-year is the equivalent of smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, the lung cells in smokers didn’t appear to add more mutations, the researchers report, suggesting that some people’s genes might make them more likely to fight mutations.

“The heaviest smokers did not have the highest mutation burden,” says Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

While it’s possible these findings could one day help doctors come up with better ways to screen for lung cancer and treat the disease, that’s still a long way off. Many more lab tests and larger studies will be needed to better pinpoint which smokers might be more prone to lung cancer and why.

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

Some smokers might not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations to DNA that would turn cells malignant and make them grow into tumors, the researchers say.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was hard for them to identify the mutations in healthy cells that might help predict future cancer risk, Jan Vijg, PhD, a senior author of the study and researcher at the University School of Medicine, Shanghai, China, said in a statement.

His team used a process called single-cell whole genome sequencing to examine cells lining the lungs of 19 smokers and 14 nonsmokers ranging in age from their pre-teens to their mid-80s. The cells came from patients who had tissue samples collected from their lungs during diagnostic testing unrelated to cancer. The scientists reported their findings in Nature Genetics.

The researchers specifically looked at cells lining the lungs because these cells can survive for years and build up mutations over time that are linked to aging and smoking.

“Of all the lung’s cell types, these are among the most likely to become cancerous,” says Simon Spivack, MD, a senior author of the study and professor at the Albert Einstein College of Medicine, New York.

Smokers had far more gene mutations that can cause lung cancer than nonsmokers, the analysis found.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” says Dr. Spivack. “This is likely one reason why so few nonsmokers get lung cancer, while 10 to 20 percent of lifelong smokers do.”

Among the smokers, people had smoked a maximum of 116 pack-years. A pack-year is the equivalent of smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, the lung cells in smokers didn’t appear to add more mutations, the researchers report, suggesting that some people’s genes might make them more likely to fight mutations.

“The heaviest smokers did not have the highest mutation burden,” says Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

While it’s possible these findings could one day help doctors come up with better ways to screen for lung cancer and treat the disease, that’s still a long way off. Many more lab tests and larger studies will be needed to better pinpoint which smokers might be more prone to lung cancer and why.

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

Some smokers might not get lung cancer because of their DNA, researchers report in a new study.

These people have genes that help limit mutations to DNA that would turn cells malignant and make them grow into tumors, the researchers say.

Scientists have long suspected that smoking leads to lung cancer by triggering DNA mutations in healthy cells. But it was hard for them to identify the mutations in healthy cells that might help predict future cancer risk, Jan Vijg, PhD, a senior author of the study and researcher at the University School of Medicine, Shanghai, China, said in a statement.

His team used a process called single-cell whole genome sequencing to examine cells lining the lungs of 19 smokers and 14 nonsmokers ranging in age from their pre-teens to their mid-80s. The cells came from patients who had tissue samples collected from their lungs during diagnostic testing unrelated to cancer. The scientists reported their findings in Nature Genetics.

The researchers specifically looked at cells lining the lungs because these cells can survive for years and build up mutations over time that are linked to aging and smoking.

“Of all the lung’s cell types, these are among the most likely to become cancerous,” says Simon Spivack, MD, a senior author of the study and professor at the Albert Einstein College of Medicine, New York.

Smokers had far more gene mutations that can cause lung cancer than nonsmokers, the analysis found.

“This experimentally confirms that smoking increases lung cancer risk by increasing the frequency of mutations, as previously hypothesized,” says Dr. Spivack. “This is likely one reason why so few nonsmokers get lung cancer, while 10 to 20 percent of lifelong smokers do.”

Among the smokers, people had smoked a maximum of 116 pack-years. A pack-year is the equivalent of smoking one pack a day for a year. The number of mutations detected in smokers’ lung cells increased in direct proportion to the number of pack-years they smoked.

But after 23 pack-years, the lung cells in smokers didn’t appear to add more mutations, the researchers report, suggesting that some people’s genes might make them more likely to fight mutations.

“The heaviest smokers did not have the highest mutation burden,” says Dr. Spivack. “Our data suggest that these individuals may have survived for so long in spite of their heavy smoking because they managed to suppress further mutation accumulation.”

While it’s possible these findings could one day help doctors come up with better ways to screen for lung cancer and treat the disease, that’s still a long way off. Many more lab tests and larger studies will be needed to better pinpoint which smokers might be more prone to lung cancer and why.

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

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

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

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

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

In states that adopted Medicaid expansion following the implementation of the Affordable Care Act (ACA), patients with cancer have improved 2-year overall survival rates, compared with patients in states that did not adopt the expansion.

The finding comes from an American Cancer Society study of more than 2 million patients with newly diagnosed cancer, published online in the Journal of the National Cancer Institute.

The analysis also showed that the evidence was strongest for malignancies with poor prognosis such as lung, pancreatic, and liver cancer, and also for colorectal cancer.

Importantly, improvements in survival were larger in non-Hispanic Black patients and individuals residing in rural areas, suggesting there was a narrowing of disparities in cancer survival by race and rurality.

“Our findings provide further evidence of the importance of expanding Medicaid eligibility in all states, particularly considering the economic crisis and health care disruptions caused by the COVID-19 pandemic,” said lead author Xuesong Han, PhD, scientific director of health services research at the American Cancer Society, in a statement. “What’s encouraging is the American Rescue Plan Act of 2021 provides new incentives for Medicaid expansion in states that have yet to increase eligibility.”

The ACA provided states with incentives to expand Medicaid eligibility to all low-income adults under 138% federal poverty level, regardless of parental status.

As of last month, just 12 states have not yet opted for Medicaid expansion, even though the American Rescue Plan Act of 2021 provides new incentives for those remaining jurisdictions. But to date, none of the remaining states have taken advantage of these new incentives.

An interactive map showing the status of Medicare expansion by state is available here. The 12 states that have not adopted Medicare expansion (as of April) are Alabama, Florida, Georgia, Kansas, Mississippi, North Carolina, South Carolina, South Dakota, Tennessee, Texas, Wisconsin, and Wyoming.  

The benefit of Medicaid expansion on cancer outcomes has already been observed in other studies. The first study to show a survival benefit was presented at the 2020 American Society of Clinical Oncology annual meeting. That analysis showed that cancer mortality declined by 29% in states that expanded Medicaid and by 25% in those that did not. The authors also noted that the greatest mortality benefit was observed in Hispanic patients.
 

Improved survival with expansion

In the current paper, Dr. Han and colleagues used population-based cancer registries from 42 states and compared data on patients aged 18-62 years who were diagnosed with cancer in a period of 2 years before (2010-2012) and after (2014-2016) ACA Medicaid expansion. They were followed through Sept. 30, 2013, and Dec. 31, 2017, respectively.

The analysis involved a total of 2.5 million patients, of whom 1.52 million lived in states that adopted Medicaid expansion and compared with 1 million patients were in states that did not.

Patients with grouped by sex, race and ethnicity, census tract-level poverty, and rurality. The authors note that non-Hispanic Black patients and those from high poverty areas and nonmetropolitan areas were disproportionately represented in nonexpansion states. 

During the 2-year follow-up period, a total of 453,487 deaths occurred (257,950 in expansion states and 195,537 in nonexpansion states).

Overall, patients in expansion states generally had better survival versus those in nonexpansion states, the authors comment. However, for most cancer types, overall survival improved after the ACA for both groups of states.

The 2-year overall survival increased from 80.6% before the ACA to 82.2% post ACA in expansion states and from 78.7% to 80% in nonexpansion states.

This extrapolated to net increase of 0.44 percentage points in expansion states after adjusting for sociodemographic factors. By cancer site, the net increase was greater for colorectal cancer, lung cancer, non-Hodgkin’s lymphoma, pancreatic cancer, and liver cancer.

For Hispanic patients, 2-year survival also increased but was similar in expansion and nonexpansion states, and little net change was associated with Medicaid expansion.

“Our study shows that the increase was largely driven by improvements in survival for cancer types with poor prognosis, suggesting improved access to timely and effective treatments,” said Dr. Han. “It adds to accumulating evidence of the multiple benefits of Medicaid expansion.”

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