Abstract PO2-20-11: Safety and efficacy of KEYNOTE-522 in combination with anti-retroviral therapy in a patient with HIV and triple-negative breast cancer

Introduction: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), accounting for about 15% of all BC. TNBC is more aggressive than other BC with a higher risk of recurrence and mortality. The current standard of care for high-risk, early-stage TNBC based on the KEYNOTE-522 trial is neoadjuvant multidrug chemotherapy (paclitaxel and carboplatin [TCb] weekly x 12 weeks and doxorubicin and cyclophosphamide [AC] Q3 weeks) with pembrolizumab (P). The trial demonstrated patients who received chemotherapy plus P had a higher pathological complete response and event-free survival compared to patients who received chemotherapy plus placebo. However, the trial excluded patients with any autoimmune disease requiring treatment within 2 years, a diagnosis of immunodeficiency or steroids within 7 days before the first treatment, or a known history of human immunodeficiency virus (HIV). While limited data exist on immune checkpoint inhibitors (ICI) in patients with immunodeficiencies, subsequent data demonstrate that patients with HIV have similar efficacy and immune-related adverse events (irAE) compared to patients without HIV, and 2017 consensus recommendations encouraged broader eligibility in clinical trials to include patients with HIV. We present one of the first reported clinical cases of a patient with HIV diagnosed with stage IIB TNBC, treated per KEYNOTE-522 and anti-retroviral therapy (ART). Clinical Case: A 55-year-old female with a medical history significant for HIV, self-detected a mass in her left breast. Diagnostic imaging demonstrated a suspicious 4.0 cm mass in the left breast without adenopathy. An ultrasound-guided biopsy of the mass revealed grade 3 invasive ductal carcinoma with ER 0%, PR < 1%, and HER-2 1+. The clinical stage was cT2N0M0, prognostic stage IIB. Genetic testing was positive for germline BRCA2 pathogenic variant. HIV PCR < 20 copies/mL and CD4 count 1.298 K/uL prior to neoadjuvant chemotherapy. The patient was adherent to HIV ART with bictegravir, emtricitabine, and tenofovir alafenamide. The patient received KEYNOTE-522, including 11 cycles of TCb-P, followed by four cycles of AC-P. Following neoadjuvant treatment, the patient underwent a left segmental mastectomy and sentinel lymph node biopsy and achieved a pathological complete response. She completed left whole breast radiation (RT) with 3DCRT plus 3DCRT tumor bed boost to a total dose of 48.06 cGy and one-year of adjuvant P. Treatment-related adverse events included grade 4 febrile neutropenia after cycle one AC without growth factor, requiring a 5-day hospitalization; and grade 3 peripheral neuropathy, resulting in discontinuation of week 12 of TCb. The patient also developed paronychia, and a pulmonary embolism after week 11 of TCb. She had no irAE. Radiation-related adverse events included grade 1 left breast dermatitis and fatigue and mild left breast soreness. Discussion: Among the subset of patients diagnosed with TNBC, the percentage of patients with HIV or immunodeficiency receiving active BC treatment is low. Safety and efficacy data for novel cancer therapeutics including ICI are limited since historically patients with HIV and other immunodeficiency states were excluded from trials. Anti-PD-1 ICI has become a key part of the standard of care for the treatment of breast cancer. Patients with HIV experience rare infectious complications and have a life expectancy near the general population with ART. We support the inclusion of patients with HIV in future clinical trials for TNBC and/or ICI and recommend treatment of patients with HIV and TNBC per standard of care in multi-disciplinary collaboration with HIV clinicians. Citation Format: Stephanie Haddad, Stephanie Graff, Matthew Hadfield, Yihong Wang, Charu Taneja, Kara Leonard, Martha Sanchez, Robert Ward, Ana Lourenco, Mary Anne Fenton. Safety and efficacy of KEYNOTE-522 in combination with anti-retroviral therapy in a patient with HIV and triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-11.