PD-L1 Inhibitor Plus Etoposide-Platinum Regimen Promising for Extensive-Stage SCLC

The results from a systematic review and meta-analysis show that a PD-L1 inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy could be an optimal first-line treatment option for patients with extensive-stage small-cell lung cancer (ES-SCLC; JAMA Netw Open. 2020 Oct 1;3(10):e2015748.).

“Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of [ES-SCLC] have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is,” wrote Ting Zhou, PhD, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China, and colleagues. 

With this in mind, Dr Zhou et al. systematically searched electronic databases from inception to December 2019. They included 14 of 199 eligible articles on head-to-head randomized clinical trials on first-line patients with ES-SCLC, along with the outcomes and toxic effects reported, including objective response rate (ORR, involving complete and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grades 3 to 5. 

The data were independently extracted and collected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and then pooled using a random-effects model.

Based on their review, PD-L1 inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy showed the most favorable OS (hazard ratio, 1.40; 95% CI, 1.09-1.80) and the best DCR (odds ratio [OR], 0.42; 95% CI, 0.21-0.81), compared to chemotherapy alone. 

Contrarily, bevacizumab plus etoposide-based chemotherapy demonstrated the best PFS (hazard ratio, 1.54; 95% CI, 1.09-2.27), but this did not translate into OS benefit. PD-L1 inhibitor plus etoposide-platinum had the highest probability of being ranked first for OS (0.87) and DCR (0.97), based on the surface under the cumulative ranking curve value.

PD-L1 inhibitors plus etoposide-platinum chemotherapy did not cause more toxic effects than chemotherapy alone (o more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31). However, bevacizumab plus etoposide-platinum regimen induced the most grades 3 to 5 AEs among all first-line treatments (OR, 4.24; 95% CI, 1.26-14.57). 

“The findings of this study suggest that the PD-L1 inhibitor plus etoposide-platinum regimen may be an optimal first-line treatment for patients with extensive-stage small-cell lung cancer,” concluded Zhou and colleagues.—Alexandra Graziano