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Purpose As cancer burden has risen worldwide, physicians, patients, and their advocates have become aware that the clinical cancer trial research paradigm is not ubiquitous. Furthermore, the number and characteristics of trials that are registered in low- and middle-income countries (LMICs) compared with that in high-income countries (HICs) are unknown. Methods We collected retrospective data on trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or with the WHO International Clinical Trial Registry Platform between 2010 and 2017. The data were then classified as trials within LMICs or HICs using definitions from the World Bank. Results Included in these analyses were 6,710 trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%) trials from LMICs and 4,759 (71%) trials from HICs (P < .001). Although the proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P = .66), the number of phase I trials in LMICs was significantly lower than that of HICs (20% v 2%; P < .001). For several LMICs with the highest mortality-to-incidence ratios for breast, lung, or cervical cancer, there were no cancer trials registered in the registration data bases searched for this work. Conclusion There are differences in access to cancer clinical trials in LMICs compared with HICs. Several factors, such as excessive cost and a lack of infrastructure and expertise, may explain these differences. [ABSTRACT FROM AUTHOR]

Purpose: As cancer burden has risen worldwide, physicians, patients, and their advocates have become aware that the clinical cancer trial research paradigm is not ubiquitous. Furthermore, the number and characteristics of trials that are registered in low- and middle-income countries (LMICs) compared with that in high-income countries (HICs) are unknown. Methods: We collected retrospective data on trials for breast, lung, and cervical cancer registered in ClinicalTrials.gov or with the WHO International Clinical Trial Registry Platform between 2010 and 2017. The data were then classified as trials within LMICs or HICs using definitions from the World Bank. Results: Included in these analyses were 6,710 trials, of which 3,164 (47%) were breast cancer trials, 3,283 (49%) were lung cancer trials, and 263 (4%) were cervical cancer trials. There were 1,951 (29%) trials from LMICs and 4,759 (71%) trials from HICs (P <.001). Although the proportion of phase III trials in HICs versus LMICs was similar (18% v 17%; P =.66), the number of phase I trials in LMICs was significantly lower than that of HICs (20% v 2%; P <.001). For several LMICs with the highest mortality-to-incidence ratios for breast, lung, or cervical cancer, there were no cancer trials registered in the registration data bases searched for this work. Conclusion: There are differences in access to cancer clinical trials in LMICs compared with HICs. Several factors, such as excessive cost and a lack of infrastructure and expertise, may explain these differences. [ABSTRACT FROM AUTHOR]

Purpose: Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort., Methods: In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4 + ≥50 cells/μL and HIV plasma RNA <200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria., Results: Thirty-two cisgender men enrolled with baseline median CD4 + T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus-related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4 + T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable)., Conclusion: Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.

Purpose: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer., Methods: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC)., Results: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS., Conclusion: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

The observation in 1981 of the emergence of Kaposi sarcoma (KS) among young men who had sex with men was one of the first harbingers of the HIV epidemic. With advances in HIV care, the incidence of HIV-associated KS (HIV + KS) has decreased over time in the United States. However, it remains a persistent malignancy among some HIV-infected populations and is one of the most common tumors in sub-Saharan Africa. Because of the relapsing and remitting nature of this cancer, patients with HIV + KS can experience significant, long-term, morbidity. Patients with severe HIV + KS may also have concurrent lymphoproliferative syndromes, malignancies, and/or infections that can contribute to mortality. Several chemotherapy agents were explored in clinical trials for HIV + KS during the early stage of the epidemic. As HIV + KS emerges with CD4 lymphopenia and immunodysregulation, T-cell-sparing options are important to consider. Here, we explore the pathogenesis of HIV + KS and the current evidence for immunotherapy and therapies that potentially target KS pathogenesis. This review provides the current landscape of therapies for HIV + KS and highlights management issues for patients with HIV and cancer., Competing Interests: Ramya RamaswamiResearch Funding: Celgene (Inst), Genentech (Inst), EMD Serono (Inst), CTI BioPharma Corp (Inst), Merck Serono (Inst) Kathryn LurainResearch Funding: Celgene (Inst), Merck (Inst), EMD Serono (Inst), CTI BioPharma Corp (Inst), Miltenyi Biotec (Inst), Janssen Oncology (Inst) Robert YarchoanResearch Funding: Celgene (Inst), Merck (Inst), Genentech (Inst), CTI BioPharma Corp (Inst), Janssen Research & Development (Inst), EMD Serono (Inst), Bristol Myers Squibb/Celgene (Inst)Patents, Royalties, Other Intellectual Property: Patent related to increase in immune surface markers by pomalidomide, lenalidomide, and related drugs in patients with KSHV-associated diseases, Various patents on vasostatin (I), KSHV vIL-6 (I), internalization of surface markers (I), calreticulin (I), and calreticulin fragments (I), Various patents including patents on anti-HIV therapies and soluble IL-2 receptor; mostly expired, Patents on the treatment of Kaposi sarcoma with IL-12, Patent(s) on the treatment of HIV and hepatitis virus with an antiviral drug and a vaccine to prevent resistance.No other potential conflicts of interest were reported.

Because of tremendous advances in HIV care, the survival of many people living with HIV (PLWH) now approaches that of the general population. This has led to a shift in the types of malignancies diagnosed among PLWH from AIDS-defining cancers during the height of the HIV epidemic toward more non-AIDS-defining cancers and age-related incidental cancers in the last 2 decades. Despite these trends, positive cancer outcomes still lag behind patients without HIV, and many PLWH never receive appropriate cancer therapy. We explore the reasons for the epidemiologic shift that has been observed, as well as the factors that influence treatment disparities. Furthermore, several studies have demonstrated similar cancer survival rates when PLWH and certain cancers receive the same treatment as those who are HIV-negative. Among possible solutions to improve cancer outcomes include increasing the inclusion of PLWH in clinical trials, using guidelines specific for the treatment of HIV-associated malignancies, and incorporating a multidisciplinary approach to cancer management in PLWH.