Comparison of First-Line Treatments for Patients With Extensive-Stage Small Cell Lung Cancer

Abstract

IMPORTANCE Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is. OBJECTIVE To clarify which first-line combination regimen is associated with the best tumor response among patients with ES-SCLC. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were systematically searched to extract eligible literature from database inception to December 2019. STUDY SELECTION Head-to-head randomized clinical trials on first-line treatments for patients with ES-SCLC were included with outcomes and toxic effects reported, including objective response rate (ORR, involving complete response and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and treatment related adverse events (TRAEs) of grades 3 to 5. Of 199 eligible articles, 14 were included. DATA EXTRACTION AND SYNTHESIS Data were independently extracted and collected by 2 reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Main outcomes were OS, PFS, DCR, ORR, and TRAEs of grades 3 to 5. RESULTS A total of 3 phase 2 and 11 phase 3 randomized clinical trials involving 4838 patients were included. Programmed cell death ligand 1 (PD-L1) inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy, compared with etoposide-based chemotherapy alone, 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). Bevacizumab plus etoposide-based chemotherapy provided the best PFS compared with etoposide-based chemotherapy alone (hazard ratio, 1.54; 95% CI, 1.09-2.27), although this was not translated into OS benefit. The addition of PD-L1 inhibitors to etoposideplatinum chemotherapy caused no more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31), while bevacizumab plus etoposide-platinum regimen induced the most TRAEs grades 3 to 5 among all first-line treatments (eg, compared with irinotecan-platinum regimen: OR, 4.24; 95% CI, 1.26-14.57). Based on the surface under the (continued) Key Points Question Is the combination of a programmed cell death ligand 1 (PD-L1) inhibitor with etoposide-platinum chemotherapy associated with better tumor response among patients with extensive-stage small cell lung cancer compared with other first-line treatments? Findings In this systematic review and network meta-analysis of 3 phase 2 and 11 phase 3 randomized clinical trials, which included 4838 patients, the combination of a PD-L1 inhibitor (durvalumab or atezolizumab) with etoposide-platinum regimen was associated with better tumor response and sa...

Efficacy and Safety of Niraparib as Maintenance Treatment in Patients With Extensive-Stage SCLC After First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study

“…2 For more than three decades and up until very recently, etoposide or irinotecan plus carboplatin or cisplatin had remained the standard first-line treatment for ES-SCLC. 3 Despite initial responsiveness to such platinum-based chemotherapies, patients tend to experience rapid progression and high rates of relapse and resistance, leading to poor survival outcomes. With conventional platinum-based chemotherapy, the median progression-free survival (PFS) of patients with ES-SCLC reported in different clinical studies mostly ranged from only 4 to 7 months with the overall survival (OS) only at 8 to 11 months.…”

Prognostic Value of 18F–FDG–PET Parameters in Patients with Small Cell Lung Cancer: A Meta-Analysis and Review of Current Literature

“…Up to 40% of patients do not achieve objective response to first-line therapy [ 2 ], but even when objective response is achieved, it is often followed by a quick and fatal relapse, and overall survival (OS) is poor [ 2 ]. The introduction of immunotherapy for first-line treatment and for treatment of relapse gives hope for an improved clinical outcome [ 3 , 4 , 5 ].…”

“…1 Kwon et al did not provide results from multivariate analysis of non-PET-parameters;2 stage was independently prognostic in multivariate analysis including SUV max , not when including MTV or TLG; 3 results from multivariate analysis available only;4 overlapping cohorts of Kim SJ and Kim MH;5 Sum of SUV max in 1-5 lesions identified by RECIST; 6 overlapping cohorts in the two studies by Oh; 7 data only available for a larger cohort of 320 patients. Mixed stage and mixed treatments 8.…”

Comparative Efficacy and Safety of Immunotherapeutic Regimens with PD-1/PD-L1 Inhibitors for Previously Untreated Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Network Meta-Analysis

“…Previous meta-analyses comparing ICIs plus chemotherapy with chemotherapy alone [ 45 , 46 ], and others comparing treatment regimens for previously untreated ES-SCLC [ 47 , 48 , 49 ] have reported that the ICIs+chemotherapy group had a better efficacy profile than the chemotherapy alone group. However, to date, no study has compared OS and PFS across six therapeutic regimens, including Pem+EP, Dur+EP, Atz+EP, AP, IP, and EP, for previously untreated ES-SCLC.…”