Abstract 1389P
Background
Anti PD1 and anti PD-L1 treatment regimens are now the standard of care for non-oncogenic driven advanced NSCLC. As people living with HIV (PLHIV) were excluded from almost all registration trials, we conducted a prospective phase II trial evaluating the safety and efficacy of Nivolumab in this population.
Methods
PLHIV with HIV viral load <200 copies/mL under antiretroviral therapy for ≥ 4 weeks and stage III-IV NSCLC who had progressed after at least one prior platinum-based doublet chemotherapy, were eligible to receive Nivolumab (3 mg/kg every 2 weeks), regardless of their CD4 cell count. The primary endpoint was disease control rate (DCR) at 8 weeks. Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Blood T-cell markers (PD1, CTLA4, TIM-3, Ki-67) were monitored at baseline, cycle 2, 3, 9, 15, 27, 51 and at the end of treatment.
Results
Sixteen patients (87.5% males), median age of 58 (range: 44-71), were enrolled between 12/2017 and 07/2019; 94% were smokers, 81% had an ECOG PS 0-1. Median duration of known HIV infection was 24 years (range 3-39), median CD4 count 384 cells/μL (range: 187-778) and HIV viral load (VL) 25 copies/mL. Histologies were adenocarcinoma (62.5%), squamous cell (31%) and others (6.5%). PD-L1 expression was negative in 9/14 tumors (64%) and positive in 5 (36%) tumors with 3 ≥50% tumoral cells. Patients received Nivolumab in 2nd (69%) and 3rd (31%) line setting for a median treatment duration of 3.5 months (range: 0.5-22.8). DCR at 8 weeks was 62.5 % (95%CI: [38.8-86.2]) with 12.5% of partial responses and 50 % of stable diseases. Median PFS and OS were 3.4 (95%CI: 1.77-5.49) and 14 (95%CI: 2.17-NR) months respectively. Most treatment-related adverse events (AE) were grade 1 or 2 (n=11, 69%), and only one patient experienced a grade 3 AE (pemphigoid at cycle 27). No opportunistic infection or unexpected clinical immune-related events were observed. Blood CD4 cell count and HIV viral load were not modified during Nivolumab treatment.
Conclusions
Nivolumab after platinum based-chemotherapy was associated with outcomes comparable to registration trials and was well tolerated in PLHIV with NSCLC.
Clinical trial identification
NCT03304093.
Editorial acknowledgement
Legal entity responsible for the study
French Cooperative Thoracic Intergroup (IFCT).
Funding
Bristol-Myers Squibb.
Disclosure
A. Lavole: Travel/Accommodation/Expenses: BMS. J. Mazieres: Advisory/Consultancy: Roche; Research grant/Funding (institution): Roche; Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BMS; Research grant/Funding (institution): BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Hengruii; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer; Advisory/Consultancy: Takeda. L. Greillier: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Roche; Travel/Accommodation/Expenses: BOEHRINGER INGELHEIM; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: TAKEDA; Advisory/Consultancy: AbbVie; Advisory/Consultancy: ASTRA ZENECA; Advisory/Consultancy: BOEHRINGER; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: TAKEDA. J-P. Spano: Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: Biogaran; Honoraria (self): Lilly; Advisory/Consultancy: Mylan; Advisory/Consultancy: Pfizer; Honoraria (self): Pierre Fabre Oncology; Advisory/Consultancy: Leopharma; Honoraria (self): Novartis; Advisory/Consultancy: Biogaran; Honoraria (self): AstraZeneca ; Honoraria (self): Gilead; Research grant/Funding (institution): MSD Avenir; Non-remunerated activity/ies: BMS. J. Cadranel: Honoraria (self): AstraZeneca/ MedImmune; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Roche/Genentech; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca/ MedImmune; Advisory/Consultancy: Genentech; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Merck Sharp & Dohme; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Lilly; Advisory/Consultancy: Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca/ MedImmune. All other authors have declared no conflicts of interest.