Efficacy and safety of PD‐1/PD‐L1 inhibitor plus chemotherapy versus chemotherapy alone as first‐line treatment for extensive‐stage small cell lung cancer: A systematic review and meta‐analysis

Abstract

Background: Immunotherapy has afforded new treatment options for extensive small cell lung cancer (ES-SCLC). However, reports on the effectiveness of immune checkpoint inhibitors (ICIs) combined with chemotherapy on survival in ES-SCLC patients are inconsistent. Therefore, we conducted a meta-analysis on the efficacy and safety of ICI combined with chemotherapy for ES-SCLC. Methods: We searched for randomized controlled clinical trials related to firstline treatment of ES-SCLC with ICI combined with chemotherapy in PUBMED, ESMO, ASCO, and WCLC since 2018. The primary outcome was overall survival (OS). Results: Four studies were included. Compared to chemotherapy alone, ICI in combination with chemotherapy as first-line treatment reduced the risk of death (hazard ratio [HR]: 0.76; 95% CI: 0.68-0.86; P < 0.00001) and disease progression (HR: 0.76; 95% CI: 0.68-0.84; P < 0.00001). The objective response rate (ORR) with ICI plus chemotherapy was significantly higher than that with chemotherapy alone (HR: 1.10; 95% CI: 1.02-1.19, P = 0.01). The duration of response (DoR) rate at one year was also better with ICI plus chemotherapy (HR: 3.46; 95% CI: 2.24-5.33; P < 0.00001). Security analysis revealed that the incidence of immune-mediated adverse events (imAEs) (HR: 3.77; 95% CI: 1.99-7.15, P < 0.0001) and grade 3/4 imAEs (HR: 7.01; 95% CI: 2.48-19.81; P = 0.0002) increased significantly with ICI plus chemotherapy. Conclusions: ICI combined with chemotherapy as first-line treatment can significantly improve the OS and progression-free survival (PFS) of ES-SCLC patients, but the toxicity caused by immunotherapy should be carefully considered.

Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline

“…After applying the eligibility criteria, 95 remained, forming the evidentiary basis for the guideline recommendations. These include 19 SRs and MAs, [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] three pooled analyses, [41][42][43] 34 phase III RCTs, 26 phase II studies, and four prospective [104][105][106][107] and nine retrospective cohort studies. [108][109][110][111][112][113][114][115][116] Primary studies already included in the SRs and MA are not included in this total.…”

Positive clinical outcomes following therapy with programmed cell death protein 1/programmed cell death ligand 1 inhibitors in neuroendocrine carcinoma of the cervix

“…Chemotherapy can induce cancer cell death, promoting tumor antigen release, increasing antigen presentation, and stimulating immune effectors, which may enhance antitumor immunity. PD-1/PD-L1 inhibitors + chemotherapy have a magnificent efficacy, which can be used in upper gastrointestinal malignancies, triple-negative breast cancer, NSCLC, SCLC, and other cancers ( Paz-Ares et al, 2018 ; Cortes et al, 2020 ; Zhang et al, 2020 ; Janjigian et al, 2021 ). In Tangjitgamaol et al’s study, 23 (96%) of 24 patients with NECC expressed vascular endothelial growth factor (VEGF) ( Tangjitgamaol et al, 2005 ).…”

Combination of chemotherapy and immune checkpoint therapy by the immunoconjugates-based nanocomplexes synergistically improves therapeutic efficacy in SCLC

“…Currently, chemo-immunotherapy is becoming one of the most promising and encouraging strategies to improve the survival outcomes of SCLC (Farid & Liu, 2020 ; Zhang et al., 2020 ; Chen et al., 2021 ). It has been demonstrated that most of chemotherapeutics were able to enhance the toll-like receptor activity and promote the DCs activation (Rocco et al., 2019 ).…”