Ryan Sugarman, MD

Ryan Sugarman, MD, Strategic Partnerships medical director, Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, discusses the key takeaways from the CheckMate-649 trial (NCT02872116) of patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma receiving nivolumab (Opdivo) combined with chemotherapy compared with chemotherapy alone in the first-line. 

In the study, patients given nivolumab plus chemotherapy experienced superior responses in overall survival (OS), progression-free survival, and even maintained their health-related quality of life for a longer duration of time than those who received chemotherapy alone.

Sugarman notes that the findings of CheckMate-649 were the basis for the 

FDA’s approval of nivolumab in April 2021

 as an initial form of treatment in this patient population. This FDA approval marks the earliest first-line immunotherapy in the gastric cancer space.

 The number 1 takeaway is the FDA approved this and it can be an important thing to consider when treating in the first-line because as I mentioned earlier, esophageal gastric cancer is sadly a deadly cancer that is one of the worldwide lead killers of cancer. The combination is just second to only lung cancer for worldwide killer cancers. When we think about our first-line therapy, we want to give the best we can because sadly, very few patients make it to a second-line therapy. Most patients don't because they had progression of disease and may not be able to tolerate further chemotherapy when they progress. For patients who have a CPS greater than or equal to 5, the benefit is very clear.

We're also happy to report that for all comers, there seems to be a benefit. I would consider the combination of chemotherapy plus immunotherapy as a standard first-line consideration for any patient with advanced esophageal gastric cancer. I would be careful in those patients who have a history of autoimmune disease or other immunotherapy concerns. If the patient is older or more frail, I would be careful in these situations too, especially if the CPS was low. But for those greater than 5, I would try in most patients to start this therapy, and I would also give when less than 5 if it is a fit for a younger patient.

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Ryan Sugarman, MD, discusses the key takeaways from the CheckMate-649 trial of patients with advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma receiving nivolumab combined with chemotherapy compared with chemotherapy alone in the first-line. 

Takeaways From CheckMate-649 in Gastric/GEJ/Esophageal Cancers

Ryan Sugarman, MD, Strategic Partnerships medical director, Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, discusses the purpose of the CheckMate 649 (NCT02872116) trial for gastroesophageal cancers (GEJ), gastric cancer, and esophageal adenocarcinoma.

The randomized phase 3 trial, CheckMate 649, looked at the addition of immunotherapy to the standard of care chemotherapy, either FOLFOX or CAPOX, in the first-line setting as treatment for advanced gastroesophageal cancers (GEJ), gastric cancer, and esophageal adenocarcinoma.

Patients in the first group received chemotherapy plus nivolumab (Opdivo) while the second group received chemotherapy alone. While a third arm was initially investigated, it was discontinued due to toxicity concerns, ultimately making FOLFOX or CAPOX plus immunotherapy versus chemotherapy alone the main focus of the study.

Findings from the study indicated that gastric or GEJ cancer who used nivolumab (Opdivo) plus chemotherapy continued to result in durable survival benefit and reported overall and progression-free survival advantages across key patient subgroups.

The CheckMate 649 was a pivotal study in gastro-esophageal cancers where it looked at the addition of immunotherapy to the standard of care, chemotherapy. The purpose of the trial is that we're not doing well enough with this esophageal gastric cancer. Sadly, this is one of the leading causes of cancer death worldwide. Despite the treatments we have, patients generally live for less than a year on average, when this trial was conducted.

 We were very happy to see that the survival was improved when we did this combination. In the frontline setting, it seems like this might be the best time to consider immunotherapy early rather than later on. We also wanted to see the progression free survival and how a patient's quality of life was while they were on this treatment compared to the standard of care chemotherapy alone. That was the purpose of us doing the Q-TWiST analysis

 This study was a phase 3 clinical trial, where there was the standard of care chemotherapy which was either FOLFOX or CAPOX. FOLFOX being the infusional fluorouracil and CAPOX being the oral capecitabine plus IV oxaliplatin plus or minus the experimental drug, nivolumab. Patients would either receive nivolumab or they would just receive the chemotherapy alone. There was a third arm with the combination immunotherapy but given toxicity concerns and seeing the same benefit, this arm was discontinued. We focused on the FOLFOX or CAPOX plus immunotherapy versus chemotherapy alone.

 This was also a multi-institutional study, and the patients were randomized based off of their PD-L1 score. We would hypothesize that patients who have a higher CPS or PDL-1 score would respond better to the immunotherapy, but we were also curious if somebody had a low score, could they also benefit because we have such limited treatment options for advanced esophageal gastric cancer. We wanted to give all patients the potential benefit, so we investigated both arms.

Ryan Sugarman, MD, discusses the design and purpose of the CheckMate 649 trial for gastroesophageal cancers, gastric cancer, and esophageal adenocarcinoma.

Ryan Sugarman, MD | Authors

Articles

Takeaways From CheckMate-649 in Gastric/GEJ/Esophageal Cancers

Survival Benefit of IO Added to Standard Chemotherapy in Gastric/GEJ/Esophageal Cancers