Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in non-small-cell lung cancer: A meta-analysis of randomized trials

Abstract

2018) Impact of PD-L1 expression, driver mutations and clinical characteristics on survival after anti-PD-1/PD-L1 immunotherapy versus chemotherapy in nonsmall-cell lung cancer: A meta-analysis of randomized trials, OncoImmunology, 7:12, e1396403, ABSTRACT Purpose: To investigate the impact of programmed death-ligand 1 (PD-L1) expression, oncogenic mutations, and clinical characteristics on survival after treatment with anti-PD-1/PD-L1 antibodies versus chemotherapy in non-small cell lung cancer (NSCLC). Patients and Methods: This meta-analysis included randomized trials comparing anti-PD-1/PD-L1 antibodies with chemotherapy. Hazard ratios (HRs) and 95% confidence interval (CI) for overall survival (OS) for the trial population and prespecified subgroups were extracted. We calculated pooled estimates of treatment efficacy using the fixed-effects or random-effects model when appropriate. All statistical tests were two sided. Results: Seven trials involving 3871 patients were included. The pooled results showed that anti-PD-1/PD-L1 immunotherapy significantly prolonged OS (HR: 0.73; 95% CI, 0.63 to 0.84) and PFS (HR: 0.84; 95% CI, 0.71 to 0.99) compared to chemotherapy. OS benefit from immunotherapy were observed in all PD-L1 expression subgroups (negative: HR, 0.79; 95% CI, 0.67 to 0.93; weak-positive: HR, 0.80; 95% CI, 0.67 to 0.95; strong-positive: HR, 0.61; 95% CI, 0.47 to 0.78). Strong-positive PD-L1 expression showed a trend towards more benefit compared to weak-positive PD-L1 expression (interaction P D 0.08). KRAS mutant (HR: 0.60; 95% CI, 0.39 to 0.93), EGFR wild-type (HR: 0.73; 95% CI, 0.61 to 0.87) and smoker (HR: 0.70; 95% CI, 0.60 to 0.83) subgroups achieved significant OS benefit from immunotherapy compared to corresponding subgroups. Survival benefit to immunotherapy was not significantly associated with histology, CNS metastases, age, gender and performance status. Conclusion: This study confirmed that treatment with anti-PD-1/PD-L1 improves overall survival compared with chemotherapy. Benefit was seen, regardless of PD-L1 expression levels; however, PD-L1 strongpositive patients trended to have greatest benefit. Patients with a KRAS mutant or EGFR wild-type tumor have improved survival benefit from immunotherapy compared with KRAS wild-type or EGFR mutant NSCLC, respectively. KEYWORDS

<p>Update on liquid biopsy in clinical management of non-small cell lung cancer</p>

“…An analysis from the trial of CheckMate-026 determined a relationship between high tissue-based TMB and better clinical benefit with nivolumab in NSCLC in the firstline. 9 Aaron et al 8 also provided evidence to show that high TMB (≥20 mutations/mb) predicted better outcomes, including ORR (46% vs 14%; P=0.0025), PFS (10 vs 2.2 months; P=0.0005), and OS(11.1 months vs not reached, P=0.0557) in comparison with low (1-5 mutations/mb) to intermediate (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) mutations/mb) TMB after receiving treatment with anti-PD1/PD-L1 monotherapy. However, obtaining the tumor tissue needed for mutations detection is always a challenge facing the advanced NSCLC patients.…”

“…The selection criterion for immune therapy is recommended to be based on the molecular status of PD-L1 expression. 7 Other potential factors, including tumor mutation burden (TMB), are also analyzed to predict the prognosis of patients receiving immune therapy according to the genomic profiles of the tumor. 8,9 Tissue biopsy was regarded as the "standard procedure" for molecular detection and was indispensable in decision-making concerning treatment for advanced NSCLC patients before 2016.…”

Generation of Genetically Engineered Mouse Lung Organoid Models for Squamous Cell Lung Cancers Allows for the Study of Combinatorial Immunotherapy

“…Despite the promising clinical activity of immune checkpoint blocking antibodies against programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1) for non-small cell lung cancer (NSCLC), only a minority of patients (~20%) show a durable response (1). Thus, there is an urgent need to improve objective response rates.…”

Identifying optimal first-line interventions for advanced non-small cell lung carcinoma according to PD-L1 expression: a systematic review and network meta-analysis

“…However, a modicum of evidence is available which suggests that those diagnosed with metastatic NSCLC and displaying PD-(L)1 over-expression may encounter an increased benefit to combinations which include immune checkpoint inhibitors that target PD-(L)1 pathways. 1 At present, the optimal combination therapy for NSCLC remains illusive which has led some to consider the prospective application of PD-(L)1 expression as a predictive biomarker, thereby narrowing target populations.…”