Managing Adverse Events in Pembrolizumab Therapy for Gastric Cancer
Yelena Y. Janjigian, MD, discusses how to manage the potential adverse events of pembrolizumab when using the recently approved combination of pembrolizumab plus trastuzumab and chemotherapy.
Yelena Y. Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, discusses how oncologists should manage potential adverse events associated with pembrolizumab (Keytruda) in the recently approved combination of pembrolizumab (Keytruda) plus trastuzumab (Herceptin) and chemotherapy in HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.1
These findings were based on the final KEYNOTE-811 trial (NCT03615326) data. In the study, this combination led to a clinically meaningful and statistically significant improvement in overall survival (OS) compared with placebo when used for the treatment of patients with HER2-positive locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, meeting the primary end point of the study.2,3
“In the original design of the KEYNOTE-811 study, most patients received either the oral form of capecitabine or an infusion of 5-FU and oxaliplatin every 3 weeks. However, in clinical practice—particularly in the United States—many patients prefer an every-2-week regimen. This is often due to increased frailty, difficulty swallowing pills, or greater toxicity associated with the oral form of fluoropyrimidines like capecitabine in the US population,” Janjigian explains.
“Because of these factors, many of us outside of a clinical trial setting opt for FOLFOX instead of CAPOX. FOLFOX follows a 2-week schedule and tends to be better tolerated. Even then, I almost never start with the full dose of FOLFOX. I typically omit the 5-FU bolus and the leucovorin bolus, as they do not significantly improve efficacy but do increase toxicity. Instead, I use infusional 5-FU along with oxaliplatin,” she adds.
According to Janjigian, this specific approach helps maintain the treatment schedule more consistently and helps to improve patient tolerance.
“Trastuzumab [Herceptin] can also be given every 2 weeks—there's substantial data supporting that. Pembrolizumab, in turn, can be administered every 6 weeks to align with the 2-week chemotherapy regimen,” she concludes.
