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The addition of nivolumab to chemotherapy demonstrated improved survival compared with chemotherapy alone after 24 months of follow up among patients with previously untreated, advanced gastric cancer (GC), gastroesophageal junction cancer (GEJC), or esophageal adenocarcinoma (EAC), according to the results of the phase 3 CheckMate 649 trial presented at the European Society for Medical Oncology (ESMO) Congress 2021.
“Longer follow-up data for nivolumab plus chemotherapy further support the use of new standard first-line treatment in patients with adenocarcinoma of G-junction, esophagus, and gastric origin,” said study presenter Yelena Y. Janjigian, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
The phase 3 CheckMate 649 trial (ClinicalTrials.gov Identifier: NCT02872116) randomly assigned 2031 patients with previously untreated, advanced GC, GEJC, or EAC to receive nivolumab plus chemotherapy, chemotherapy, or nivolumab plus ipilimumab. Patients were enrolled regardless of PD-L1 or microsatellite instability (MSI) status, but were excluded if their disease was HER2-positive. The coprimary endpoints were overall survival (OS) and progression-free survival (PFS).
The majority of patients had GC (70%), while 17.8% of patients had GEJC and 12.5% had EAC. There were 59.8% of patients with PD-L1 combined positive score (CPS) greater than or equal to 5 and 2.8% with MSI-high tumors.
The nivolumab plus ipilimumab arm stop enrollment early due to higher rates of toxicity compared with the other arms.
Nivolumab plus chemotherapy continued to result in prolonged OS in the all-randomized population with a median of 13.8 months compared with 11.6 months with chemotherapy alone (hazard ratio [HR], 0.79; 95% CI, 0.71-0.88). OS was similar in the PD-L1 CPS greater than or equal to 5 population, with medians of 14.4 and 11.1 months with nivolumab plus chemotherapy or chemotherapy, respectively (HR, 0.70; 95% CI, 0.61-0.81).
PFS also remained significantly longer with nivolumab plus chemotherapy compared with chemotherapy in the all-randomized population, with a medians of 7.7 and 6.9 months, respectively (HR, 0.79; 95% CI, 0.70-0.89). These results were similar for the PD-L1 CPS greater than or equal to 5 population (HR, 0.70; 95% 0.60-0.81).
Objective response rate (ORR) was also higher in patients who received nivolumab plus chemotherapy, at 58% compared with 46% with chemotherapy alone, with a duration of response of 8.5 and 6.9 months, respectively, in the all-randomized population.
The combination of nivolumab plus ipilimumab did not meet its primary endpoint. In the all-randomized population, the median OS was similar between the combination arm compared with chemotherapy at 11.7 and 11.8 months, respectively (HR, 0.91; 95% CI, 0.77-1.07). Overall survival was also similar in the PD-L1 CPS greater than or equal to 5 population.
However, when patients were stratified by MSI-high, the median OS was not yet reached with nivolumab plus ipilimumab compared with 10.0 months with chemotherapy (unstratified HR, 0.28; 95% CI, 0.08-0.92).
The rate of serious treatment-related adverse events (TRAEs) of grade 3 to 4 severity occurred among 17% of patients in the nivolumab plus chemotherapy arm, 10% in the chemotherapy arm, and 23% in the nivolumab plus ipilimumab arm compared with 12% in its corresponding chemotherapy arm.
“Nivolumab plus chemotherapy continues to demonstrate clinically meaningful benefit in our first-line treated patients,” Dr Janjigian concluded.
Disclosures: This research was supported by Bristol Myers Squibb. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Janjigian YY, Ajani JA, Moehler M, et a. Nivolumab (NIVO) plus chemotherapy (Chemo) or ipilimumab (IPI) vs chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): CheckMate 649 study. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA7.