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PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy.

ABSTRACT: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxel-cisplatin chemotherapy. A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Among the 12 SNPs investigated, PD-L1 rs2297136T?>?C and rs4143815C?>?G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T?>?C was significantly associated with both better chemotherapy response and better OS, and the rs4143815C?>?G had a significantly better response to chemotherapy. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype (ht4) carrying variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes. Patients with at least one ht4 had significantly better chemotherapy response and OS compared to those without ht4. PD-L1 rs2297136T?>?C and rs4143815C?>?G polymorphisms may be useful for the prediction of clinical outcome of 1(st) line paclitaxel-cisplatin chemotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the chemotherapy outcome of NSCLC patients.

SUBMITTER: Lee SY

PROVIDER: S-EPMC4867646 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy.

Lee Shin Yup SY Jung Deuk Kju DK Choi Jin Eun JE Jin Cheng Cheng CC Hong Mi Jeong MJ Do Sook Kyung SK Kang Hyo-Gyoung HG Lee Won Kee WK Seok Yangki Y Lee Eung Bae EB Jeong Ji Yun JY Shin Kyung Min KM Yoo Seung Soo SS Lee Jaehee J Cha Seung Ick SI Kim Chang Ho CH Park Jae Yong JY

Scientific reports 20160516

This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxel-cisplatin chemotherapy. A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. A ...[more]

PMID: 27181838

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Project description:BackgroundCurrently, there has been no direct comparison between programmed cell death protein 1 (PD-1) inhibitors plus different chemotherapy regimens in first-line treatments for advanced gastric cancer (AGC). This study performed a network meta-analysis (NMA) to evaluate the efficacy and safety of PD-1 inhibitors plus oxaliplatin- or cisplatin-based chemotherapy.MethodsPubMed, Embase, and the Cochrane Central Register were used to seek a series of phase III randomized controlled trials (RCTs) studying on first-line PD-1 inhibitors plus chemotherapy and phase III RCTs comparing first-line oxaliplatin and cisplatin-based chemotherapy for AGC to perform NMA. The main outcome was overall survival (OS) and other outcomes included progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAEs).ResultsEight eligible RCTs involving 5723 patients were included. Compared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy could prolong the OS without statistical significance (hazard ratio [HR]: 0.82, 95% credible interval [CI]: 0.63-1.06). However, for patients with combined positive score (CPS) ≥ 1, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged the OS (HR: 0.75, 95% CI: 0.57-0.99). PFS in PD-1 inhibitors plus oxaliplatin-based chemotherapy was significantly longer than that in PD-1 inhibitors plus cisplatin-based chemotherapy (HR: 0.72, 95% CI: 0.53-0.99). Regarding safety, the incidence of ≥ 3 TRAEs was similar between PD-1 inhibitors plus oxaliplatin-based chemotherapy and PD-1 inhibitors plus cisplatin-based chemotherapy (RR: 0.86, 95% CI: 0.66-1.12). The surface under the cumulative ranking area curve (SUCRA) indicated that PD-1 inhibitors plus oxaliplatin-based chemotherapy ranked first for OS (97.7%), PFS (99.3%), and ORR (89.0%). For oxaliplatin-based regimens, there was no significant difference between nivolumab plus oxaliplatin-based chemotherapy and sintilimab plus oxaliplatin-based chemotherapy in terms of OS, PFS, ORR, and ≥3 TRAEs.ConclusionCompared with PD-1 inhibitors plus cisplatin-based chemotherapy, PD-1 inhibitors plus oxaliplatin-based chemotherapy significantly prolonged PFS. Considering both efficacy and safety, PD-1 inhibitors plus oxaliplatin-based chemotherapy might be a better option in the first-line treatment for AGC.

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PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy.

Publications

PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel-cisplatin chemotherapy.

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