Sintilimab improves survival in advanced gastric, gastroesophageal junction cancer
Click Here to Manage Email Alerts
Key takeaways:
- Sintilimab plus chemotherapy conferred longer median OS compared with placebo plus chemotherapy.
- Patients with PD-L1 combined positive scores of 5 or greater experienced the biggest benefit.
Adding sintilimab to chemotherapy improved survival compared with placebo among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma, phase 3 study results published in JAMA showed.
The strongest survival benefit appeared to be among the subset of patients with a PD-L1 combined positive score of 5 or greater, according to researchers.
“Among patients with previously untreated advanced gastric or gastroesophageal junction adenocarcinoma, adding sintilimab to standard chemotherapy was associated with significantly improved overall survival and progression-free survival compared with placebo plus standard chemotherapy,” Jianming Xu, MD, of The Fifth Medical Center, Chinese PLA General Hospital, in Beijing, China, and researchers wrote.
Background and methodology
Limited treatments exist for patients diagnosed with gastric and gastroesophageal junction cancers; however, the addition of sintilimab (Innovent Biologics/Eli Lilly) to chemotherapy has shown promising efficacy.
The double-blind, placebo-controlled ORIENT-16 trial evaluated the saftey and efficacy of sintilimab among patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers. Researchers randomly assigned study participants to receive either sintilimab plus chemotherapy or placebo plus chemotherapy.
Researchers also analyzed the effectiveness of the two treatments arms among a subset of patients with a PD-L1 combined positive score of 5 or greater.
Among the 650 patients (median age, 59 years; 74.3% men) in the trial enrolled through 62 hospitals in China, 327 patients received sintilimab and 323 patients received placebo, in addition to capecitabine and oxaliplatin every 3 weeks for a maximum of 6 cycles; however, maintenance therapy continued for up to 2 years.
OS time from randomization served as the study’s primary endpoint.
Results, next steps
Researchers observed that the addition of sintilimab to chemotherapy improved OS compared with placebo (median, 15.2 months vs. 12.3 months; stratified HR = 0.77; 95% CI, 0.63-0.94) among the general patient population.
Upon further analysis, researchers noted that patients with a combined positive score of 5 or greater (n = 397) exhibited statistically greater OS results than those with scores lower than 5 (median, 18.4 months vs. 12.9 months; HR = 0.66; 95% CI, 0.5-0.86).
The most common grade 3 or higher treatment-related adverse events included decreased platelet count (sintilimab, 24.7%; placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1%; placebo, 18.8%) and anemia (sintilimab, 12.5%; placebo, 8.8%).
Researchers acknowledged several potential study limitations, such as the trial being a multicenter study performed throughout China, making the potential generalizability of the results for other populations unclear.
Next steps
The combination of a PD-L1 inhibitor and chemotherapy has become a standard of care across the world for patients with gastric or gastroesophageal junction adenocarcinoma because of the CheckMate 649 study, which showed significant improvements in OS and PFS with nivolumab (Opdivo, Bristol Myers Squibb) plus chemotherapy, Xu and colleagues wrote.
The ORIENT-16 study randomly assigned patients to receive an alternative anti-PD-1 antibody to nivolumab, and yet still found similar results in that survival benefits persisted with the addition of immunotherapy to standard chemotherapy, especially among patients with higher PD-L1 expression.
Collapse
Click Here to Manage Email Alerts