Historically, PLWH have been excluded from participation in oncology trials, which may affect generalizability of findings. represent 70% of these deaths and NECA will increase with aging of the PLWH populace.3 During the past decade, NECA clinical trials of immune checkpoint inhibitors (ICIs) have changed the treatment landscape of many cancers. Historically, PLWH have been excluded from participation in oncology trials, which may impact generalizability of findings. In this systematic review and meta-analysis, we investigated characteristics of ICI trials associated with inclusion of PLWH. NECA Methods We performed a systematic search using the key word checkpoint to identify prospective trials involving programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) or cytotoxic T-lymphocyteCassociated protein 4 ICIs published in 6 high-profile general medicine and oncology journals (Table 1) between January 1, 2016 and March 31, 2019. Two impartial reviewers (D.V.A. and H.S.) assessed articles, including supplements and protocols, as well as ClinicalTrials.gov data to determine whether PLWH were eligible for enrollment. In cases of ambiguity, results were discussed with a third reviewer (D.H.). This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Table 1. Characteristics of Included Trials New England Journal of MedicineLancetLancet OncologyJournal of Clinical OncologyJAMAJAMA OncologyAnnals of Oncologyvalues were 2-tailed, and statistical significance was defined as less than .05. No corrections were made for multiple significance screening. Data analysis was performed using SPSS statistical software version 25.0 (IBM) and Revmen review software version 5.3 (Cochrane) and conducted from June 1, 2019, to June 21, 2019. Results Of 569 articles screened, 126 articles were trials of ICIs. We excluded 8 studies: 4 studies were duplicates, and 4 studies involved ICIs other than PD-1, PD-L1, or cytotoxic T-lymphocyteCassociated protein 4. Our final analysis included 118 articles comprising 30?693 patients. Demographic data for the 118 articles are summarized in Table 1. For PLWH eligibility analysis, we excluded 11 trials owing to unavailability of data. Of 107 trials with PLWH inclusion criteria data, 5 trials (4.7%, 258 patients) allowed enrollment of PLWH. All 5 trials that allowed PLWH were academic, whereas no trials sponsored by a pharmaceutical organization included PLWH (odds ratio, 259.77; 95% CI, 26.25-2570.61; Value
Funding Pharmaceutical industry87087259.77 (26.25-2570.61)<.001 Academic155201 [Reference]Publication date 2016240241 [Reference]NA 2017291300.16 (0.01-8.53).37 2018343370.18 (0.02-1.91).16 2019151160.08 (0.01-4.48).22Combination of ICI with other treatment No654690.43 (0.04-4.07).47 Yes371381 [Reference]Involved PD-1 and PD-L1 ICIs No8190.34 (0.03-3.42).36 Yes944981 [Reference]Tumor type Lung220224.88 (0.58-40.74).14 Melanoma150154.15 (0.41-41.39).22 Urothelial130133.96 (0.36-43.14).26 Renal cell carcinoma7073.45 (0.18-63.66).40 Head and neck squamous cell carcinoma6170.58 (0.04-8.11).58 Other394431 [Reference]NALine of treatment First collection metastatic352370.78 (0.12-4.91).80 Other673701 [Reference]Trial phase 1360366.93 (1.13-42.24).04 2385431 [Reference]NA 3280285.76 (0.90-36.53).06 Open in a separate window Abbreviations: ICI, immune checkpoint inhibitors; NA, not applicable; PD-1, programmed cell death 1; PD-L1, programmed-death ligand 1; OR, odds ratio. Discussion Limitations of our study include the lack of multivariable adjustment and absence of reporting the justification for PLWH exclusion. Nonetheless, our results demonstrate an almost universal exclusion of PLWH from trials involving ICIs. There are no good justifications for this practice. A 2019 systematic review4 exhibited that the security profile of PD-1 or PD-L1 ICIs in PLWH was similar to that of the general populace, with no unusual adverse events. A study by Uldrick et al5 of a phase 1 trial including 30 patients with HIV and advanced malignancy treated with pembrolizumab reported a security profile in keeping with studies of participants without HIV. While academic studies were more likely to allow PLWH, even within Rabbit Polyclonal to CK-1alpha (phospho-Tyr294) this group only 5 trials permitted PLWH. Whereas the reasons for PLWH exclusion are not disclosed in any protocols, we suspect that this practice results from dogma rather than reasoned decision. A recent American Society of Clinical Oncology task force6 recommended inclusion of PLWH in oncology trials, particularly patients with T-cell CD4+ counts of 350 cells/L or higher, who constitute a group with intact immunological function and NECA survival in keeping with the general populace. In contrast, the NECA exclusion of PLWH is usually unsupported by current data, denies patients the benefit of ICI therapy, and is ethically unjustifiable. We advocate for any broader inclusion of these patients in oncology trials..