PMID- 28275115 OWN - NLM STAT- MEDLINE DCOM- 20180214 LR - 20220410 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 22 IP - 4 DP - 2017 Apr TI - Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis. PG - 470-479 LID - 10.1634/theoncologist.2016-0419 [doi] AB - BACKGROUND: Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS: PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. RESULTS: A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. CONCLUSION: PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer. CI - (c) AlphaMed Press 2017. FAU - Nishijima, Tomohiro F AU - Nishijima TF AD - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA Tomohiro.Nishijima@unchealth.unc.edu. FAU - Shachar, Shlomit S AU - Shachar SS AD - Division of Oncology, Rambam Health Care Campus, Haifa, Israel. FAU - Nyrop, Kirsten A AU - Nyrop KA AD - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA. FAU - Muss, Hyman B AU - Muss HB AD - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20170308 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (B7-H1 Antigen) RN - 0 (CD274 protein, human) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (Nivolumab) RN - 52CMI0WC3Y (atezolizumab) RN - DPT0O3T46P (pembrolizumab) SB - IM MH - Antibodies, Monoclonal/adverse effects/therapeutic use MH - Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use MH - B7-H1 Antigen/*antagonists & inhibitors/genetics MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics/pathology MH - Disease-Free Survival MH - Drug-Related Side Effects and Adverse Reactions/classification/*pathology MH - Humans MH - Melanoma/*drug therapy/genetics/pathology MH - Nivolumab MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors/genetics PMC - PMC5388381 OTO - NOTNLM OT - Chemotherapy OT - Meta-analysis OT - PD-1/PD-L1 inhibitor OT - Systematic review OT - Toxicity COIS- Disclosures of potential conflicts of interest may be found at the end of this article. EDAT- 2017/03/10 06:00 MHDA- 2018/02/15 06:00 PMCR- 2018/04/01 CRDT- 2017/03/10 06:00 PHST- 2016/10/22 00:00 [received] PHST- 2016/12/16 00:00 [accepted] PHST- 2017/03/10 06:00 [pubmed] PHST- 2018/02/15 06:00 [medline] PHST- 2017/03/10 06:00 [entrez] PHST- 2018/04/01 00:00 [pmc-release] AID - theoncologist.2016-0419 [pii] AID - ONCO12077 [pii] AID - 10.1634/theoncologist.2016-0419 [doi] PST - ppublish SO - Oncologist. 2017 Apr;22(4):470-479. doi: 10.1634/theoncologist.2016-0419. Epub 2017 Mar 8.