Anti‐PD1 versus anti‐PD‐L1 immunotherapy in first‐line therapy for advanced non‐small cell lung cancer: A systematic review and meta‐analysis

Abstract

Background Due to the increasing number of trials with immune checkpoint inhibitors (ICIs) in the first‐line therapy of non‐small cell lung cancer (NSCLC) patients, we performed a systematic review and meta‐analyses to investigate the difference between anti PD‐1 and PD‐L1 antibodies, used alone or in combination with chemotherapy, through adjusted indirect analysis to minimize the potential bias regarding overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and grade 3–5 adverse events (AEs). Methods A systematic review of studies reporting clinical outcomes and toxicity associated with first‐line therapy employing anti‐PD1 or anti‐PD‐L1 antibodies alone, or in combination with chemotherapy, to treat metastatic, treatment‐naïve NSCLC patients was performed. Primary outcomes were OS, PFS, ORR and grade 3–5 AEs. We used a random‐effects model to generate pooled estimates for proportions. Meta‐analyses using pooled risk ratios were performed for binary outcomes from comparative studies with the random effects model. Results A total of 13 eligible studies met our eligibility criteria, including 7673 patients. In the ICI‐chemotherapy combination subgroup, we observed that anti‐PD1 therapy was associated with better OS (p = 0.022) and PFS (p = 0.029) compared with anti‐PD‐L1 therapy. In the monotherapy subgroup, there was no statistical difference between the use of anti‐PD‐1 and anti‐PD‐L1 for OS and PFS. With regard to ORR and toxicity, in the ICI‐chemotherapy combination subgroup, we observed a trend of better ORR (p = 0.12) with the use of anti‐PD1 therapy and less frequent grade 3–5 AEs compared to the use of anti‐PD‐L1 therapy (p = 0.0302). In the monotherapy subgroup, there was no statistical difference between the use of anti‐PD‐1 and anti‐PD‐L1 regarding ORR and toxicity. Conclusions Our study suggests that PD‐1 drug plus chemotherapy is superior to anti‐PD‐L1 plus chemotherapy for NSCLC; nevertheless, as monotherapy, both strategies appear to be similar.

Mutational signature analysis in non-small cell lung cancer patients with a high tumor mutational burden

“…One of these biomarkers is the expression of PD-L1 on tumor cells, indicating eligibility for immune checkpoint inhibitor therapy [ 2 , 3 ]. However, PD-L1 expression as a predictive biomarker for response to immune checkpoint blockade (ICB) is fairly unreliable due to dynamic and heterogeneous expression in the tumor microenvironment, divergent assay interpretation and lack of PD-L1 platform standardization [ 4 – 8 ]…”

Drug Regimen for Patients after a Pneumonectomy

“…Depending on the study population, further research may be needed due to the limited tolerance in post-pneumonectomy patients before assessing generalizability. In terms of toxicity, it has been reported that PD-1 or PD-L1 antibodies are associated with lower risk of grade 3-5 adverse events compared to chemotherapy (OR 0.45; 95% CI: 0.38-0.54 for PD-1, HR 0.54; 95% CI: 0.40-0.72 for PD-L1) [44]. When combined with chemotherapy, PD-1 antibodies showed less frequent grade 3-5 adverse events than PD-L1 antibodies (p = 0.0302) although there was no statistically significant difference as monotherapies [44].…”

“…In terms of toxicity, it has been reported that PD-1 or PD-L1 antibodies are associated with lower risk of grade 3-5 adverse events compared to chemotherapy (OR 0.45; 95% CI: 0.38-0.54 for PD-1, HR 0.54; 95% CI: 0.40-0.72 for PD-L1) [44]. When combined with chemotherapy, PD-1 antibodies showed less frequent grade 3-5 adverse events than PD-L1 antibodies (p = 0.0302) although there was no statistically significant difference as monotherapies [44]. While more studies are needed to determine the optimal drug regimen of immunotherapeutic agents with or without chemotherapy or radiotherapy, PD-1 antibodies may be a better treatment option to be incorporated into post-pneumonectomy management.…”

What if Bevacizumab was discontinued! Can IMpower130 be exchanged for IMpower150 for advanced non-squamous NSCLC patients with PD-L1 <50% and without genomic mutations?

“…There were two meta-analysis studies compared between PD-1 and PD-L1 inhibitors in NSCLC in 2nd line setting, and they concluded that anti-PD-1 drugs had better performance than anti-PD-L1 ICIs [34,35]. Another meta-analysis by Brito and colleagues based on 13 clinical trials involved ICIs for treatment-naïve advanced NSCLC patients, suggested the superiority of anti-PD-1 over PD-L1 inhibitors when there was a combination with chemotherapy, but as monotherapy, there was no difference between them [36]. Brito hypothetically proposed that the difference could be due to the inhibition of PD-1 which would block both PD-L1 and PD-L2 and that was not achievable by PD-L1 blockade.…”