PD-1 Inhibitors Safe, Effective in Patients With HIV and Non-Small Cell Lung Cancer
None of the patients experienced grade 3 or 4 immune-related adverse events or immune reconstitution inflammatory syndrome.
The programmed death receptor 1 (PD-1) inhibitors nivolumab and pembrolizumab may be safe and effective for patients with non-small-cell lung cancer (NSCLC) and HIV, according to a study recently published in the Journal of Thoracic Oncology.1
HIV is an independent risk factor for lung cancer,2 and lung cancer has emerged as one of the leading overall causes of death in people living with HIV.3 Although several PD-1 pathway inhibitors have recently been approved for treatment of advanced NSCLC, patients with HIV have been excluded from nearly all clinical trials of immune checkpoint inhibitors in lung cancer, resulting in a lack of data on safety and efficacy of PD-1 pathway inhibitors in this population.4-7 Previously, there has only been 3 case reports of patients with NSCLC and HIV who were treated with an immune checkpoint inhibitor.8-10 The current study describes 7 cases of people with NSCLC and HIV who were treated with PD-1 inhibitors.
Clinicopathologic data and treatment outcomes of patients with HIV and NSCLC at the Beth Deaconess Medical Center and the Dana-Farber Cancer Institute were collected from retrospective chart review. Included were 7 patients with metastatic NSCLC and HIV infection who were treated with PD-1 inhibitors; 5 received pembrolizumab and 2 received nivolumab. Of these patients, 6 were male and 1 was female (age range: 43-59) and all had a history of tobacco use and lung adenocarcinoma histology. In all cases, immune checkpoint inhibitor therapy was administered intravenously at standard doses: pembrolizumab 200 mg every 3 weeks or nivolumab 3 mg/kg every 2 weeks. All patients received antiretroviral therapy (ART) while on anti-PD-1 treatment. The patients who were already receiving ART continued their HIV regimen without a change or interruption of ART.
Partial responses to immune checkpoint inhibitors were observed in 3 of the 7 cases. Among 4 patients with a PD-1 ligand tumor proportion score of 50%, 3 had a partial response, 2 currently remain on treatment, and 1 patient who had an ongoing response died as a result of complications unrelated to immunotherapy treatment. Furthermore, 2 patients had stable disease and 2 patients had progressive disease as a best overall response.
Treatment with the PD-1 inhibitor was generally well tolerated in all 7 patients. No grade 3 to 4 immune-related adverse events or treatment-related deaths occurred while on anti-PD-1 therapy, and autoimmune thyroiditis was not observed in these 7 people. Additionally, in patients for whom follow up values were available, CD4 counts and HIV viral load did not change markedly while on treatment with a PD-1 inhibitor.
Study authors concluded that even though additional research is necessary, “In this small cohort of patients, anti-PD-1 therapy appears to be safe, and in some cases, very effective in HIV-positive patients with lung cancer.”
Disclosures: Dr Costa received consultancy fees from AstraZeneca, Takeda and Pfizer. Dr Hammond received funding from Merck. Dr Awad received grants and personal fees from Bristol Myers Squibb and personal fees from Merck and AstraZeneca.
- Ostios-Garcia L, Faig J, Leonardi GC, et al. Safety and efficacy of PD-1 inhibitors among HIV-positive patients with non-small-cell lung cancer [published online April 6, 2018]. J Thorac Oncol. doi: 10.1016/j.jtho.2018.03.031
- Kirk GD, Merlo C, O'Driscoll P, et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis. 2007;45(1):103-110.
- Reddy KP, Kong CY, Hyle EP, et al. Lung cancer mortality associated with smoking and smoking cessation among people living with HIV in the United States. JAMA Intern Med. 2017;177:1613-1621.
- Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med. 2015;373(17):1627-1639.
- Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med. 2015;373(2):123-135.
- Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540-1550.
- Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389(10066):255-265.
- McCullar B, Alloway T, Martin M. Durable complete response to nivolumab in a patient with HIV and metastatic non-small cell lung cancer. J Thorac Dis. 2017;9(6):E540-E542.
- Hentrich M, Schipek-Voigt K, Jäger H, et al. Nivolumab in HIV-related non-small-cell lung cancer. Ann Oncol. 2017;28(11):2980.
- Guihot A, Marcelin A-G, Massiani M-A, et al. Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer. Ann Oncol. 2018;29(2):517-518.