Opdivo and chemo confirmed long-term survival in superior gastric, gastroesophageal junction or esophageal most cancers.
Chinese language sufferers with superior gastric most cancers, gastroesophageal junction (GEJ) most cancers, or esophageal adenocarcinoma demonstrated a clinically significant, long-term enchancment in general survival (OS) in contrast with chemotherapy alone after first-line remedy with Opdivo (nivolumab) plus chemotherapy in the course of the part 3 CheckMate 649 trial.
Up to date knowledge offered on the 2025 Gastrointestinal Cancers Symposium demonstrated that, at a minimal follow-up of 61.2 months for the Chinese language inhabitants handled in the course of the research, Opdivo plus chemotherapy (99 sufferers) generated a median OS of 14.3 months in contrast with 10.3 months for chemotherapy alone (109 sufferers) The 60-month OS charges have been 20% and seven%, respectively.
Amongst sufferers with a PD-L1 mixed optimistic rating (CPS) of at the least 5, these within the Opdivo group (75 sufferers) achieved a median OS of 15.5 months versus 9.6 months for sufferers within the chemotherapy group (81 sufferers). The respective 60-month OS charges have been 24% and eight%.
Glossary:
Thrombocytopenia: low platelet rely.
Neutropenia: low neutrophil rely.
General survival (OS): how lengthy sufferers reside after prognosis.
Development-free survival (PFS): how lengthy sufferers reside with out illness development.
Goal response charge (ORR): share of sufferers exhibiting tumor shrinkage.
Full response (CR): tumor is totally gone.
Partial response (PR): tumor shrinks by at the least 30%.
Secure illness (SD): tumor neither shrinks nor grows.
Progressive illness (PD): tumor grows.
Period of response (DOR): how lengthy a response lasts.
ECOG efficiency standing: a measure of a affected person’s common well being.
PD-L1 mixed optimistic rating (CPS): a measure of PD-L1 expression on tumor cells.
Immunologic etiology: immune system-related reason for illness.
The OS profit with Opdivo plus chemotherapy was constant throughout prespecified subgroups within the Chinese language inhabitants.
Within the general inhabitants, the median progression-free survival (PFS) was 8.3 months for the Opdivo group versus 5.6 months for the chemotherapy alone group. Within the inhabitants with a PD-L1 CPS of at the least 5, the median PFS was 8.5 months and 4.3 months for Opdivo plus chemotherapy and chemotherapy alone, respectively.
“These prolonged follow-up outcomes align with the general CheckMate 649 trial inhabitants, reinforcing Opdivo plus chemotherapy as the usual first-line remedy for Chinese language sufferers with superior gastric most cancers, GEJ most cancers, [or] esophageal adenocarcinoma,” lead research creator Dr. Lin Shen, and colleagues wrote in a poster presentation of the information.
Shen is vice chairman of Medical Oncology at Beijing Most cancers Hospital and Peking College, in addition to deputy director at Beijing Institute for Most cancers Analysis in China.
In April 2021, the FDA authorized Opdivo mixed with choose varieties of chemotherapy for the frontline remedy of sufferers with superior or metastatic gastric most cancers, GEJ most cancers, and esophageal adenocarcinoma, based mostly on prior knowledge from CheckMate 649.
Security and Extra Efficacy Knowledge for the Chinese language Inhabitants
No new security alerts with Opdivo plus chemotherapy have been reported with longer-term follow-up. Any-grade treatment-related uncomfortable side effects (TRAEs) occurred in 99% of sufferers within the Opdivo group versus 94% of sufferers within the management group. The charges of grade 3 (extreme) or 4 (life-threatening) TRAEs have been 66% and 50%, respectively. Severe any-grade TRAEs have been reported in 26% of sufferers within the experimental group versus 13% of sufferers within the chemotherapy alone group. The respective charges of grade 3 or 4 severe TRAEs have been 19% and 10%.
The most typical grade 3 or 4 TRAEs reported within the Opdivo group included decreased neutrophil rely (17%), decreased platelet rely (7%), thrombocytopenia (7%), decreased white blood cell rely (6%), anemia (6%) and neutropenia (6%).
Within the chemotherapy alone group, probably the most frequent grade 3 or 4 TRAEs comprised decreased platelet rely (11%), decreased neutrophil rely (11%), neutropenia (8%) and vomiting (5%).
TRAEs led to remedy discontinuation in 51% of sufferers within the Opdivo group versus 26% of sufferers within the chemotherapy alone group. 4 treatment-related deaths (4%) have been reported within the experimental group versus 1 treatment-related loss of life (1%) within the management group.
Notably, grade 3 or 4 TRAEs with potential immunologic etiology occurred in not more than 7% of Chinese language sufferers within the Opdivo plus chemotherapy group throughout organ classes; no grade 5 (loss of life) occasions occurred in both group.
Within the general inhabitants, the ORR was 66% within the Opdivo group versus 45% within the chemotherapy alone group. Within the experimental group, the whole response (CR), partial response (PR), secure illness (SD) and progressive illness (PD) charges have been 17%, 49%, 25% and 9%, respectively. These respective charges have been 8%, 37%, 30% and 14% within the management group.
The median period of response (DOR) within the general inhabitants was 12.5 months for the Opdivo group versus 5.6 months for the chemotherapy alone group.
Within the PD-L1 CPS of at the least 5 inhabitants, the ORR was 68% within the Opdivo group versus 48% within the chemotherapy alone group. The respective CR, PR, SD and PD within the Opdivo group have been 19%, 49%, 23% and 9%. These respective charges have been 11%, 37%, 25% and 17% within the management group. The median DOR on this inhabitants was 12.5 months and 6.9 months for the experimental and management teams, respectively.
The OS, PFS and ORR advantages with the Opdivo routine have been constant throughout totally different PD-L1 CPS subgroups.
Amongst all randomly assigned sufferers within the experimental group, sufferers who responded to Opdivo plus chemotherapy (49 sufferers) skilled a median OS of 21.5 months in contrast with 9 months for many who had SD or PD (33 sufferers). Within the chemotherapy group, responders (42 sufferers) achieved a median OS of 14.5 months versus 9.1 months for non-responders (34 sufferers).
Within the inhabitants of sufferers with a PD-L1 CPS of at the least 5, those that responded to Opdivo plus chemotherapy (40 sufferers) had a median OS of 23.3 months versus 11.5 months for many who didn’t reply to the experimental routine (23 sufferers). Within the chemotherapy group, the median OS was 13.1 months for responders (33 sufferers) versus 9.1 months for non-responders (22 sufferers).
CheckMate 649 Overview
The randomized, open-label, world part 3 research enrolled sufferers with beforehand untreated, unresectable, superior or metastatic gastric most cancers, GEJ most cancers and esophageal adenocarcinoma. Sufferers weren’t permitted to have HER2-positive illness, and an ECOG efficiency standing of 0 to 1 was required.
Sufferers have been randomly assigned in a 1:1:1 trend. Within the first experimental group, sufferers acquired Opdivo at 360 milligrams (mg) together with XELOX (oxaliplatin and capecitabine) as soon as each three weeks; or Opdivo at 240 mg plus FOLFOX (oxaliplatin, leucovorin and fludarabine) as soon as each two weeks. Within the management group, sufferers acquired chemotherapy alone within the type of XELOX as soon as each three weeks or FOLFOX as soon as each two weeks. Therapy continued till illness development, unacceptable toxicity, withdrawal of consent or finish of research.
Within the Opdivo group, 15% of sufferers acquired FOLFOX, and 85% got XELOX. These charges have been 13% and 87%, respectively, within the management group.
The research additionally included a second experimental group the place sufferers acquired Opdivo at 1 mg per kilogram (mg/kg) plus Yervoy (ipilimumab) at 3 mg/kg as soon as each three weeks for 4 cycles, adopted by Opdivo alone at 240 mg as soon as each two weeks.
Blinded impartial central evaluate–assessed PFS and OS within the inhabitants of sufferers with a PD-L1 CPS of at the least 5 served because the trial’s twin main finish aim. Secondary finish objectives included OS and PFS within the general inhabitants, the inhabitants of sufferers with a PD-L1 CPS of at the least 1 and the inhabitants of sufferers with a PD-L1 CPS of at the least 10; and general response charge.
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Reference
“First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) versus chemo in sufferers (pts) with superior gastric most cancers, gastroesophageal junction most cancers, and esophageal adenocarcinoma (GC/GEJC/EAC): 5-year (y) follow-up of Chinese language pts from CheckMate 649.” By Dr. Shen L et al. J Clin Oncol. 2025; suppl.392
