The review of 5 phase 3 randomized controlled trials found that overall, the combination treatments improved survival outcomes while eliciting more, but manageable, side effects.
As various immune-oncology combination treatments continue to be assessed in clinical trials for use in first-line advanced esophageal cancer, researchers of a meta-analysis published in International Immunopharmacology have found which combinations yield the strongest efficacy.
The review of 5 phase 3 randomized controlled trials found that overall, the combination treatments improved survival outcomes while eliciting more, but manageable, side effects. As a whole, adding a PD-1 inhibitor to chemotherapy was associated with improved overall survival (OS) (HR: 0.69, 95% CI: 0.62–0.76, P < .001), progression-free survival (PFS) (HR: 0.62, 95% CI: 0.55–0.70, P < .001) and objective response rate (ORR) (risk ratio [RR]: 1.41, 95% CI: 1.23–1.62, P < .001) among the 3000 patients included in the studies.
While PD- 1/PD-L1 inhibitors have emerged as promising treatments in esophageal cancer—pembrolizumab is currently approved in the second-line setting—preliminary data suggest that combining PD-1 inhibitors with chemotherapy may have a synergistic effect. To date, there have been no head-to-head comparisons of different chemo-immunotherapy combinations in the first-line setting.
Across the combinations,toripalimab plus chemotherapy (tori-chemo) yielded the strongest OS results relative to chemotherapy (HR: 0.58, 95% CI: 0.43-0.78) followed by sintilimab plus chemotherapy (sinti-chemo) (HR: 0.63, 95% CI: 0.51-0.78) and camrelizumab plus chemotherapy (camre-chemo) (HR: 0.70, 95% CI: 0.56-0.88).
Sinti-chemo and camre-chemo were associated with the most improved PFS relative to chemotherapy (HR: 0.56, 95% CI: 0.46-0.68). Notably, nivolumab plus chemotherapy (nivo-chemo) demonstrated significantly shorter PFS than tori-chemo (HR: 0.72, 95% CI: 0.51-1.00), sinti-chemo (HR: 0.69, 95% CI: 0.51-0.94) and camre-chemo (HR: 0.69, 95% CI: 0.51-0.94).
Subgroup analyses found significantly improved OS among patients with PD-L1 tumor-positive score (TPS) ≥ 10% and longer PFS among patients with PD-L1 combined positive score (CPS) ≥ 10.
“This led us to consider which method of assessing PD-L1 expression had better prognostic value in esophageal cancer. At present, it is still controversial, with some studies using TPS and others using CPS,” explained the researchers. “Based on our analysis, PD-L1 TPS may be more meaningful in OS and PD-L1 CPS probably more predictive in PFS for advanced esophageal cancer patients who used IO-chemotherapy combination as first-line treatment. Further studies are still needed to explore the association between PD-L1 expression and the efficacy of PD-1 inhibitors.”
Highest ORR compared with chemotherapy was seen with nivo-chemo (RR: 1.73, 95% CI:1.40-2.14), followed by pembrolizumab plus chemotherapy (pembro-chemo) (RR:1.54,95%CI:1.27-1.87) and sinti-chemo (RR:1.47, 95% CI: 1.28-1.70). Camre-chemo had the lower ORR rate among the combinations.
The chemo-immunotherapy combinations were associated with an increase in serious adverse events (AEs) (pooled RR: 1.36, 95% CI: 1.15-1.61, P < .001) and treatment discontinuation due to AEs (pooled RR: 1.82, 95% CI: 1.55-2.14, P < .001). Among the combinations, camre-chemo and pembro-chemo were associated with relatively lower grade ≥3 AEs.
Immune-mediated AEs of any grade (pooled RR: 2.01, 95% CI: 1.35-2.98, P = .001) and immune-mediated AEs of grade ≥3 (pooled RR: 2.33, 95% CI: 1.36-3.97, P = .002) were both higher with chemo-immunotherapy combinations.
Reference
Li Z, Sun Y, Lai M, Zhou Y, Qiu M. Efficacy and safety of PD-1 inhibitors combined with chemotherapy as first-line therapy for advanced esophageal cancer: A systematic review and network meta-analysis. Int Immunopharmacol. Published online April 20, 2022. doi:10.1016/j.intimp.2022.108790
A Focus on Women: AUA Best Posters Highlight Female Athletes, Prenatal Care, and Women in Urology
May 9th 2024Three posters from the American Urological Association (AUA) 2024 Annual Meeting focused on urinary incontinence in female athletes, prenatal care for fetuses with spina bifida in California, and the experiences of women residents at the Brady Urological Institute.
Read More
CMS Medicare Final Rule: Advancing Benefits, Competition, and Consumer Protection
May 7th 2024On this episode of Managed Care Cast, we're talking with Karen Iapoce, senior director of government products and programs at ZeOmega, about the recent CMS final rule on Medicare Part D and Medicare Advantage.
Listen
Patients With Advanced, Recurrent Melanoma May Experience Lasting AEs From ICM Therapy
May 9th 2024A cross-sectional, mixed-methods study found that adverse effects (AEs) can occur even after 1 year of treatment with immune checkpoint modulator (ICM) therapy in patients with melanoma.
Read More
Diagnostic Oversights Limit Luspatercept Benefits in MDS
May 8th 2024Investigators of a retrospective study encourage colleagues to utilize molecular testing for patients with an established diagnosis of lower-risk myelodysplastic syndromes (MDS), to be sure they don’t miss out on treatments, like luspatercept, for which they qualify.
Read More
Integrating RECIST and Clinician Approaches Boosts NSCLC Research
May 8th 2024Outcomes among patients with stage IV non–small cell lung cancer as evaluated within clinical trials via Response Evaluation Criteria in Solid Tumors (RECIST) and clinician response criteria in observational studies were compared for their concordance and reliability.
Read More