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CHICAGO – The American Society of Clinical Oncology recently wrapped its annual meeting in Chicago. Here, I highlight some presentations that stood out to me.
A first-line treatment for metastatic colorectal cancer
The plenary session did not disappoint. In abstract LBA1, investigators presented first-line treatment for patients with metastatic colorectal cancer who were randomized to receive mFOLFOX6 with either bevacizumab or panitumumab in RAS wild-type positive patients. This was the phase 3 PARADIGM trial.
The primary outcome for this study was overall survival. It included 823 patients who were randomized 1:1 with a subset analysis of whether the primary tumor was on the left or right side of the colon. At 61 months follow-up, the median overall survival results for left-sided colon cancer was 38 months versus 34 months. It was statistically significant favoring the panitumumab arm. It improved the curable resection rate for patients with left-sided tumors from 11% in the bevacizumab arm to 18% in the panitumumab arm. Interestingly, patients randomized with right-sided tumors showed no difference in overall survival. The investigator, Takayuki Yoshino, MD, PhD, National Cancer Center Hospital East, Kashiwa, Japan, said the study findings support the use of mFOLFOX6 with panitumumab in left-sided RAS wild type as first-line therapy in metastatic colorectal patients.
A possible new standard of care in breast cancer
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, received a standing ovation and deserved it. In the phase 3 clinical trial DESTINY-Breast04 (abstract LBA3), she demonstrated that trastuzumab deruxtecan (T-DXd) for patients with metastatic breast cancer who were HER2 low (IHC 1+ or 2+ ISH-), led to a statistically significant and clinically meaningful benefit in both progression free survival and overall survival. In this trial, patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy. All patients had at least one to two lines of chemotherapy before entering the trial. Hormone-positive patients were allowed if they had already received and failed, or progressed on hormone therapy.
Previously, most patients were treated either with eribulin with some receiving capecitabine, gemcitabine or taxane, or hormone therapy if hormone positive.
The progression-free survival was 10.1 versus 5.4 months in hormone-positive patients, and in all patients (hormone receptor positive or negative), there was a likewise improvement of 9.9 versus 5.1 months progression free survival.
Overall survival was equally impressive. In the hormone receptor–positive patients, the hazard ratio was 0.64 with a 23.9 versus 17.5 month survival. If all patients were included, the HR was again 0.64 with 23.4 versus 16.8 month survival. Even the triple-negative breast cancer patients had a HR of 0.48 with 18.2 versus 8.3 months survival. Adverse events were quite tolerable with some nausea, some decreased white count, and only an interstitial lung disease of grade 2 or less in 12%.
Trastuzumab deruxtecan is a targeted treatment which, in addition to striking its target, also targets other tumor cells that are part of the cancer. The results of this study may lead to a new standard of care of this patient population.
The study by Dr. Modi and colleagues was simultaneously published in the New England Journal of Medicine.
Improving outcomes in multiple myeloma
In abstract LBA4, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, asks if autologous stem cell transplant (ASCT) can improve outcomes after induction with an RVD regimen (lenalidomide, bortezomib, and dexamethasone) and lenalidomide (Revlimid) maintenance for newly diagnosed patients with multiple myeloma in the DETERMINATION study.
The take home here was quite interesting. In fact, there is no difference in overall survival if patients get this standard RVD/lenalidomide maintenance induction with or without ASCT. However, the progression free survival was better with ASCT: 46 versus 67 months (improvement of 21 months). However, there were some caveats. There was toxicity and change in quality of life for a while in those patients receiving ASCT as would be expected. Furthermore, the study only allowed 65 years old or younger and ASCT may not be wise for older patients. The discussant made a strong point that African Americans tend to have higher risk disease with different mutations and might also be better served by have ASCT later.
The conclusion was that, given all the new therapies in myeloma for second line and beyond, ASCT should be a discussion with each new patient and not an automatic decision.
This study was simultaneously published in the New England Journal of Medicine.
Adagrasib promising for pretreated patients with NSCLC with KRAS mutation
In patients with advanced or metastatic non–small cell lung cancer (NSCLC), adagrasib was found to be well tolerated and “demonstrates promising efficacy” for patients with the KRAS G12C mutation (KRYSTAL-1, abstract 9002). This was a phase 2 registration trial of 116 patients who were treated with 600 mg of adagrasib twice orally. Patients all had previous chemotherapy or immunotherapy or both. The overall response rate was a surprisingly good 43% (complete response and partial response). Disease control was an incredible 80% if stable disease was included. The duration of response was 8.5 months, progression-free survival was 6.5 months, and overall survival was 12.6 months. Furthermore, 33% of those with brain metastases had a complete response or partial response.
The take-home message is that, since 15% of NSCLC metastatic patients are KRAS mutant G12C, we should be watching for such patients in our biomarker analysis. While we have sotorasib – approved by the Food and Drug Administration for NSCLC – the results of this study suggests we may have another new molecule in the same class.
Neoadjuvant chemotherapy with immunotherapy for NSCLC
It may be time to consider neoadjuvant chemotherapy with immunotherapy, such as nivolumab, for patients with NSCLC in order to achieve the best response possible.
In NADIM II, investigators led by Mariano Provencio-Pulla, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, confirmed the superiority of chemotherapy with immunotherapy for patients with resectable stage IIIA NSCLC. NADIM included patients with resectable stage IIIA/B NSCLC who were randomized 2:1 to receive carboplatin taxol neoadjuvant therapy with or without nivolumab before and after surgery. The pathological complete response rates overall were 36% versus 7%, favoring the nivolumab arm, but even higher pCR rates occurred in patients with PD-L1 over 50%.
In closing, always check MMR, KRAS, BRAF, and HER2. For wild-type left-sided mCRC, consider FOLFOX or FOLFIRI with an anti-EGFR. For KRAS mutant or right-sided colon tumor, consider FOLFOX or FOLFIRI with bevacizumab, followed by maintenance 5FU or capecitabine, with or without bevacizumab.
CHICAGO – The American Society of Clinical Oncology recently wrapped its annual meeting in Chicago. Here, I highlight some presentations that stood out to me.
A first-line treatment for metastatic colorectal cancer
The plenary session did not disappoint. In abstract LBA1, investigators presented first-line treatment for patients with metastatic colorectal cancer who were randomized to receive mFOLFOX6 with either bevacizumab or panitumumab in RAS wild-type positive patients. This was the phase 3 PARADIGM trial.
The primary outcome for this study was overall survival. It included 823 patients who were randomized 1:1 with a subset analysis of whether the primary tumor was on the left or right side of the colon. At 61 months follow-up, the median overall survival results for left-sided colon cancer was 38 months versus 34 months. It was statistically significant favoring the panitumumab arm. It improved the curable resection rate for patients with left-sided tumors from 11% in the bevacizumab arm to 18% in the panitumumab arm. Interestingly, patients randomized with right-sided tumors showed no difference in overall survival. The investigator, Takayuki Yoshino, MD, PhD, National Cancer Center Hospital East, Kashiwa, Japan, said the study findings support the use of mFOLFOX6 with panitumumab in left-sided RAS wild type as first-line therapy in metastatic colorectal patients.
A possible new standard of care in breast cancer
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, received a standing ovation and deserved it. In the phase 3 clinical trial DESTINY-Breast04 (abstract LBA3), she demonstrated that trastuzumab deruxtecan (T-DXd) for patients with metastatic breast cancer who were HER2 low (IHC 1+ or 2+ ISH-), led to a statistically significant and clinically meaningful benefit in both progression free survival and overall survival. In this trial, patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy. All patients had at least one to two lines of chemotherapy before entering the trial. Hormone-positive patients were allowed if they had already received and failed, or progressed on hormone therapy.
Previously, most patients were treated either with eribulin with some receiving capecitabine, gemcitabine or taxane, or hormone therapy if hormone positive.
The progression-free survival was 10.1 versus 5.4 months in hormone-positive patients, and in all patients (hormone receptor positive or negative), there was a likewise improvement of 9.9 versus 5.1 months progression free survival.
Overall survival was equally impressive. In the hormone receptor–positive patients, the hazard ratio was 0.64 with a 23.9 versus 17.5 month survival. If all patients were included, the HR was again 0.64 with 23.4 versus 16.8 month survival. Even the triple-negative breast cancer patients had a HR of 0.48 with 18.2 versus 8.3 months survival. Adverse events were quite tolerable with some nausea, some decreased white count, and only an interstitial lung disease of grade 2 or less in 12%.
Trastuzumab deruxtecan is a targeted treatment which, in addition to striking its target, also targets other tumor cells that are part of the cancer. The results of this study may lead to a new standard of care of this patient population.
The study by Dr. Modi and colleagues was simultaneously published in the New England Journal of Medicine.
Improving outcomes in multiple myeloma
In abstract LBA4, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, asks if autologous stem cell transplant (ASCT) can improve outcomes after induction with an RVD regimen (lenalidomide, bortezomib, and dexamethasone) and lenalidomide (Revlimid) maintenance for newly diagnosed patients with multiple myeloma in the DETERMINATION study.
The take home here was quite interesting. In fact, there is no difference in overall survival if patients get this standard RVD/lenalidomide maintenance induction with or without ASCT. However, the progression free survival was better with ASCT: 46 versus 67 months (improvement of 21 months). However, there were some caveats. There was toxicity and change in quality of life for a while in those patients receiving ASCT as would be expected. Furthermore, the study only allowed 65 years old or younger and ASCT may not be wise for older patients. The discussant made a strong point that African Americans tend to have higher risk disease with different mutations and might also be better served by have ASCT later.
The conclusion was that, given all the new therapies in myeloma for second line and beyond, ASCT should be a discussion with each new patient and not an automatic decision.
This study was simultaneously published in the New England Journal of Medicine.
Adagrasib promising for pretreated patients with NSCLC with KRAS mutation
In patients with advanced or metastatic non–small cell lung cancer (NSCLC), adagrasib was found to be well tolerated and “demonstrates promising efficacy” for patients with the KRAS G12C mutation (KRYSTAL-1, abstract 9002). This was a phase 2 registration trial of 116 patients who were treated with 600 mg of adagrasib twice orally. Patients all had previous chemotherapy or immunotherapy or both. The overall response rate was a surprisingly good 43% (complete response and partial response). Disease control was an incredible 80% if stable disease was included. The duration of response was 8.5 months, progression-free survival was 6.5 months, and overall survival was 12.6 months. Furthermore, 33% of those with brain metastases had a complete response or partial response.
The take-home message is that, since 15% of NSCLC metastatic patients are KRAS mutant G12C, we should be watching for such patients in our biomarker analysis. While we have sotorasib – approved by the Food and Drug Administration for NSCLC – the results of this study suggests we may have another new molecule in the same class.
Neoadjuvant chemotherapy with immunotherapy for NSCLC
It may be time to consider neoadjuvant chemotherapy with immunotherapy, such as nivolumab, for patients with NSCLC in order to achieve the best response possible.
In NADIM II, investigators led by Mariano Provencio-Pulla, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, confirmed the superiority of chemotherapy with immunotherapy for patients with resectable stage IIIA NSCLC. NADIM included patients with resectable stage IIIA/B NSCLC who were randomized 2:1 to receive carboplatin taxol neoadjuvant therapy with or without nivolumab before and after surgery. The pathological complete response rates overall were 36% versus 7%, favoring the nivolumab arm, but even higher pCR rates occurred in patients with PD-L1 over 50%.
In closing, always check MMR, KRAS, BRAF, and HER2. For wild-type left-sided mCRC, consider FOLFOX or FOLFIRI with an anti-EGFR. For KRAS mutant or right-sided colon tumor, consider FOLFOX or FOLFIRI with bevacizumab, followed by maintenance 5FU or capecitabine, with or without bevacizumab.
CHICAGO – The American Society of Clinical Oncology recently wrapped its annual meeting in Chicago. Here, I highlight some presentations that stood out to me.
A first-line treatment for metastatic colorectal cancer
The plenary session did not disappoint. In abstract LBA1, investigators presented first-line treatment for patients with metastatic colorectal cancer who were randomized to receive mFOLFOX6 with either bevacizumab or panitumumab in RAS wild-type positive patients. This was the phase 3 PARADIGM trial.
The primary outcome for this study was overall survival. It included 823 patients who were randomized 1:1 with a subset analysis of whether the primary tumor was on the left or right side of the colon. At 61 months follow-up, the median overall survival results for left-sided colon cancer was 38 months versus 34 months. It was statistically significant favoring the panitumumab arm. It improved the curable resection rate for patients with left-sided tumors from 11% in the bevacizumab arm to 18% in the panitumumab arm. Interestingly, patients randomized with right-sided tumors showed no difference in overall survival. The investigator, Takayuki Yoshino, MD, PhD, National Cancer Center Hospital East, Kashiwa, Japan, said the study findings support the use of mFOLFOX6 with panitumumab in left-sided RAS wild type as first-line therapy in metastatic colorectal patients.
A possible new standard of care in breast cancer
Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, received a standing ovation and deserved it. In the phase 3 clinical trial DESTINY-Breast04 (abstract LBA3), she demonstrated that trastuzumab deruxtecan (T-DXd) for patients with metastatic breast cancer who were HER2 low (IHC 1+ or 2+ ISH-), led to a statistically significant and clinically meaningful benefit in both progression free survival and overall survival. In this trial, patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of chemotherapy. All patients had at least one to two lines of chemotherapy before entering the trial. Hormone-positive patients were allowed if they had already received and failed, or progressed on hormone therapy.
Previously, most patients were treated either with eribulin with some receiving capecitabine, gemcitabine or taxane, or hormone therapy if hormone positive.
The progression-free survival was 10.1 versus 5.4 months in hormone-positive patients, and in all patients (hormone receptor positive or negative), there was a likewise improvement of 9.9 versus 5.1 months progression free survival.
Overall survival was equally impressive. In the hormone receptor–positive patients, the hazard ratio was 0.64 with a 23.9 versus 17.5 month survival. If all patients were included, the HR was again 0.64 with 23.4 versus 16.8 month survival. Even the triple-negative breast cancer patients had a HR of 0.48 with 18.2 versus 8.3 months survival. Adverse events were quite tolerable with some nausea, some decreased white count, and only an interstitial lung disease of grade 2 or less in 12%.
Trastuzumab deruxtecan is a targeted treatment which, in addition to striking its target, also targets other tumor cells that are part of the cancer. The results of this study may lead to a new standard of care of this patient population.
The study by Dr. Modi and colleagues was simultaneously published in the New England Journal of Medicine.
Improving outcomes in multiple myeloma
In abstract LBA4, Paul G. Richardson, MD, of the Dana-Farber Cancer Institute, Boston, asks if autologous stem cell transplant (ASCT) can improve outcomes after induction with an RVD regimen (lenalidomide, bortezomib, and dexamethasone) and lenalidomide (Revlimid) maintenance for newly diagnosed patients with multiple myeloma in the DETERMINATION study.
The take home here was quite interesting. In fact, there is no difference in overall survival if patients get this standard RVD/lenalidomide maintenance induction with or without ASCT. However, the progression free survival was better with ASCT: 46 versus 67 months (improvement of 21 months). However, there were some caveats. There was toxicity and change in quality of life for a while in those patients receiving ASCT as would be expected. Furthermore, the study only allowed 65 years old or younger and ASCT may not be wise for older patients. The discussant made a strong point that African Americans tend to have higher risk disease with different mutations and might also be better served by have ASCT later.
The conclusion was that, given all the new therapies in myeloma for second line and beyond, ASCT should be a discussion with each new patient and not an automatic decision.
This study was simultaneously published in the New England Journal of Medicine.
Adagrasib promising for pretreated patients with NSCLC with KRAS mutation
In patients with advanced or metastatic non–small cell lung cancer (NSCLC), adagrasib was found to be well tolerated and “demonstrates promising efficacy” for patients with the KRAS G12C mutation (KRYSTAL-1, abstract 9002). This was a phase 2 registration trial of 116 patients who were treated with 600 mg of adagrasib twice orally. Patients all had previous chemotherapy or immunotherapy or both. The overall response rate was a surprisingly good 43% (complete response and partial response). Disease control was an incredible 80% if stable disease was included. The duration of response was 8.5 months, progression-free survival was 6.5 months, and overall survival was 12.6 months. Furthermore, 33% of those with brain metastases had a complete response or partial response.
The take-home message is that, since 15% of NSCLC metastatic patients are KRAS mutant G12C, we should be watching for such patients in our biomarker analysis. While we have sotorasib – approved by the Food and Drug Administration for NSCLC – the results of this study suggests we may have another new molecule in the same class.
Neoadjuvant chemotherapy with immunotherapy for NSCLC
It may be time to consider neoadjuvant chemotherapy with immunotherapy, such as nivolumab, for patients with NSCLC in order to achieve the best response possible.
In NADIM II, investigators led by Mariano Provencio-Pulla, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, confirmed the superiority of chemotherapy with immunotherapy for patients with resectable stage IIIA NSCLC. NADIM included patients with resectable stage IIIA/B NSCLC who were randomized 2:1 to receive carboplatin taxol neoadjuvant therapy with or without nivolumab before and after surgery. The pathological complete response rates overall were 36% versus 7%, favoring the nivolumab arm, but even higher pCR rates occurred in patients with PD-L1 over 50%.
In closing, always check MMR, KRAS, BRAF, and HER2. For wild-type left-sided mCRC, consider FOLFOX or FOLFIRI with an anti-EGFR. For KRAS mutant or right-sided colon tumor, consider FOLFOX or FOLFIRI with bevacizumab, followed by maintenance 5FU or capecitabine, with or without bevacizumab.
AT ASCO 2022