FDA Approves Nivolumab With Chemotherapy for Gastric and Esophageal Cancer

Esophageal adenocarcinoma.

The FDA has granted approval to nivolumab (Opdivo®, Bristol-Myers Squibb Company) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the initial treatment of patients with advanced/metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

“Standard first-line chemotherapy options for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer result in poor overall survival,” wrote Markus Moehler, MD, PhD, Head of Gastrointestinal Oncology at the Mainz University Clinic in Germany, and colleagues, in their presentation abstract for the initial results of the phase 3 CheckMate 649 trial (NCT02872116), on which the approval was based. “Nivolumab plus chemotherapy represents a potential new standard first-line treatment option for these patients.”

CheckMate 649 enrolled 1,581 patients with previously untreated advanced/metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma, regardless of programmed death ligand 1 (PD-L1) expression. Upon randomization, 789 patients received nivolumab in combination with chemotherapy consisting of FOLFOX (fluorouracil/leucovorin/oxaplatin) or capecitabine/oxaliplatin, while 792 patients received chemotherapy alone. Patients in the experimental group received 240 mg nivolumab plus FOLFOX every two weeks or 360 mg nivolumab plus capecitabine/oxaliplatin every three weeks. The primary end points were overall survival and progression-free survival.

In 955 patients who had a PD-L1 combined positive score of ≥5, nivolumab plus chemotherapy significantly improved median overall survival (14.4 vs 11.1 months) and progression-free survival (7.7 vs 6.0 months) compared with chemotherapy alone. In all randomized patients, nivolumab plus chemotherapy also significantly improved overall survival (13.8 vs 11.6 months).

Adverse events occurring in at least 20% of patients receiving nivolumab with fluoropyrimidine- and platinum-containing chemotherapy included peripheral neuropathy, nausea, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, constipation, and musculoskeletal pain.

“Nivolumab is the first programmed cell death protein 1 (PD-1) inhibitor to demonstrate superior overall survival and progression-free survival in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma, with a manageable safety profile,” concluded Dr. Moehler and colleagues in their presentation of the trial’s first results at the European Society for Medical Oncology (ESMO) Virtual Congress in September 2020.

The recommended nivolumab doses are 360 mg every three weeks, in combination with fluoropyrimidine- and platinum-containing chemotherapy every three weeks; or 240 mg every two weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy every two weeks. 

For More Information

Moehler M, Shitara K, Garrido M, et al (2020). Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Ann Oncol (ESMO Virtual Congress Abstracts), 31(suppl_4):S1142-S1215. Abstract LBA6_PR. DOI:10.1016/annonc/annonc325

Clinicaltrials.gov (2020). Efficacy study of nivolumab plus ipilimumab or nivolumab plus chemotherapy against chemotherapy in stomach cancer or stomach/esophagus junction cancer (CheckMate649). NLM identifier: NCT02872116.

Opdivo® (nivolumab) prescribing information (2021). Bristol-Myers Squibb Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125554s091lbl.pdf

US Food & Drug Administration (2021). FDA approves first immunotherapy for initial treatment of gastric cancer. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-initial-treatment-gastric-cancer

US Food & Drug Administration (2021). FDA approves nivolumab in combination with chemotherapy for metastatic gastric cancer and esophageal adenocarcinoma. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-combination-chemotherapy-metastatic-gastric-cancer-and-esophageal

Image credit: Mikael Häggström, MD. Licensed under CC0 1.0

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