Opdivo plus chemo in sufferers with superior gastric or esophageal cancers confirmed improved 5-year general survival in comparison with chemotherapy alone.
Amongst sufferers with superior gastric and gastroesophageal junction (GEJ) most cancers, or esophageal adenocarcinoma (EAC), remedy with first-line Opdivo (nivolumab) plus chemotherapy demonstrated deep responses and an general survival (OS) profit versus chemotherapy alone, in keeping with 5-year follow-up information from the part 3 CheckMate 649 trial.
The up to date outcomes shared throughout the 2025 ASCO Gastrointestinal (GI) Cancers Symposium confirmed that at a minimal follow-up of 60.1 months, the median OS was 14.4 months with Opdivo plus chemotherapy versus 11.1 months with chemotherapy alone in sufferers with a PD-L1 mixed optimistic rating (CPS) of 5 or greater. The 5-year OS charges have been 16% and 6%, respectively. OS and progression-free survival (PFS) on this subgroup have been the first finish factors of the trial.
Throughout all sufferers randomized to Opdivo plus chemotherapy or the management arm of chemotherapy alone, the median OS at 5 years was 13.7 months versus 11.6 months, respectively. The 5-year OS charges throughout all sufferers have been 12% versus 6%, respectively.
The PFS profit beforehand reported with the addition of Opdivo to chemotherapy was additionally maintained with longer follow-up. Amongst sufferers with a PD-L1 CPS of 5 or better, the median PFS at 5 years was 8.3 months within the investigative arm versus 6.1 months within the management arm. Throughout all randomized sufferers, the 5-year median PFS was 7.8 months versus 6.9 months, respectively.
Glossary:
Median length of response (mDOR): the size of time {that a} affected person with a illness experiences a optimistic response to a remedy earlier than their illness progresses once more.
Goal response charge (ORR): sufferers who’ve a partial response or full response to the remedy inside a sure time frame.
Total survival (OS): the typical size of time sufferers are alive after the beginning of remedy.
Open label: a sort of analysis the place each the contributors and researchers are conscious of which remedy is being administered.
PD-L1 mixed optimistic rating (CPS): a technique utilized in most cancers pathology to evaluate the extent of PD-L1 expression on tumor cells.
Development-free survival (PFS): the size of time throughout and after remedy {that a} affected person lives with the illness nevertheless it doesn’t worsen.
5-year response information highlighted the sturdiness of the clinically significant exercise of the Opdivo mixture on this frontline setting. The target response charge (ORR) within the CPS better than or equal to five subgroup was 60% within the Opdivo plus chemo arm in contrast with 45% within the management arm. The median length of response (mDOR) was 9.6 versus months 7.0 months, respectively. Amongst all sufferers, the ORR was 58% versus 46% and the mDOR was 8.5 versus 6.9 months, respectively.
There have been no new security indicators noticed with the prolonged follow-up, in keeping with Janjigian. The commonest grade 3 (extreme) or 4 (life-threatening) treatment-related unwanted effects within the Opdivo plus chemotherapy arm have been neutropenia (16%), decreased neutrophil rely (11%), anemia (6%) and elevated lipase (6%). Within the chemotherapy-alone arm, the commonest grade 3 or 4 treatment-related unwanted effects have been neutropenia (13%), decreased neutrophil rely (9%), diarrhea (3%), peripheral neuropathy (3%), anemia (3%) and vomiting (3%).
“To our information, these outcomes characterize the longest follow-up in a part 3 trial of a programmed death-1 inhibitor plus chemo in superior GC, GEJC and EAC and proceed to assist [Opdivo] plus chemotherapy as commonplace first-line remedy,” mentioned presenting creator Dr. Yelena Y. Janjigian, chief of the Gastrointestinal Oncology Service at Memorial Sloan Kettering Most cancers Heart, in New York, New York.
In April 2021, the FDA accepted Opdivo to be used together with choose kinds of chemotherapy within the frontline remedy of this affected person inhabitants primarily based on earlier findings from CheckMate 649.
Concerning the CheckMate 649 Trial
The open-label, randomized, international part 3 CheckMate 649 trial enrolled sufferers with beforehand untreated, unresectable, superior or metastatic gastric most cancers, GEJ or EAC. Sufferers had no identified HER2 positivity and an ECOG efficiency standing of 0 or 1.
Research enrollment occurred at 175 hospitals and most cancers facilities throughout 29 international locations. Sufferers have been randomized in a to one of many following remedy cohorts:
- Opdivo (360 milligrams, mg) plus oxaliplatin at 130 mg per sq. meter (mg/m2) on day 1 and capecitabine at 1000 mg/m2 twice day by day from days 1 to 14 (XELOX routine) each three weeks or Opdivo at 240 mg plus oxaliplatin at 85 mg/m2, leucovorin at 400 mg/m2 and fluorouracil (FU) at 400 mg/m2 on day 1 and FU at 1200 mg/m2 day by day on days 1 and a couple of (FOLFOX routine) each two weeks (789 sufferers).
- XELOX each three weeks or FOLFOX each two weeks (833 sufferers).
- Opdivo at 1 mg per kilogram (kg) plus Yervoy (ipilimumab) at 3 mg/kg each three weeks for 4 cycles adopted by Opdivo at 240 mg each two weeks (409 sufferers).
On the 2025 Symposium, Janjigian shared 5-year information for the Opdivo plus chemotherapy arm and the management arm of chemotherapy alone. Baseline traits between these two arms have been properly balanced. Throughout each arms, the median age was roughly 62 years, 70% of sufferers have been male, three-quarters of sufferers have been non-Asian and roughly 58% of sufferers had an ECOG efficiency standing of 1. The first tumor location at preliminary prognosis throughout all sufferers was 70% gastric most cancers, 16% GEJ and 14% EAC.
Roughly 18% of sufferers in every arm had signet ring cell carcinoma, 96% had metastatic illness, 40% had liver metastases and 24% had peritoneal metastases. Sixteen % of sufferers in every arm had tumor cell PD-L1 expression 1% or better and three% had microsatellite instability excessive standing. About 54% of sufferers in every arm obtained FOLFOX and 46% obtained XELOX.
The twin major finish factors have been OS and PFS within the subset of sufferers with a PD-L1 CPS of 5 or greater. Secondary finish factors comprised OS in these with a PD-L1 CPS of 1 or greater and the all-randomized inhabitants; OS in these with a PD-L1 CPS of 10 or greater; blinded impartial central assessment–assessed PFS in these with a PD-L1 CPS of 10 or greater, 1 or greater and the all-randomized inhabitants; and ORR. Security and high quality of life served because the exploratory finish factors of the trial. The information cutoff information for the outcomes offered was Could 28, 2024.
References:
“Nivolumab (NIVO) + chemotherapy (chemo) vs chemo as first-line (1L) remedy for superior gastric most cancers/gastroesophageal junction most cancers/esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up outcomes from CheckMate 649.” By Dr. Janjigian Y, et al. J Clin Oncol. 2025; suppl.398
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