Abstract P3-02-04: Phase II study of Pembrolizumab Maintenance treatment in patients with HER2-negative inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) after response to chemotherapy
Authors: Iwase Toshiaki , Alexander Angela , Chiv Vivian , Kai Megumi , Kida Kumiko , Parker Charla , Marx Angela N. , Cohen Evan , Gao Hui , Reuben James , Wang Xiaoping , Krishnamurthy Savitri , Liu Diane , Shen Yu , Ramirez David , Tripathy Debu , Booser Daniel , Yam Clinton , Valero Vicente , Lim Bora , Ueno Naoto T. , Willey Jie S. 
Published: March 2023

Abstract
Accumulating physical and hematologic toxicities make the indefinite use of chemotherapy unfeasible for many patients with metastatic/recurrent HER2– IBC or TNBC. Whether maintenance immunotherapy has a role in the treatment of these patients is unclear. We conducted a single-arm phase II trial of pembrolizumab monotherapy in patients with metastatic/recurrent HER2– IBC or TNBC (regardless of their PD-L1 expression status) and report here the clinical data from this trial. Methods: Eligible patients were enrolled between 2015 and 2022 and had had a CR, a PR, or SD after a minimum of 3 cycles of chemotherapy for metastatic/recurrent disease. PD-L1 expression status was not used to determine eligibility. Patients received 200 mg of pembrolizumab every 3 weeks (q3w) until disease progression, intolerable toxicity, or 2 years. In late 2021, the study was amended to allow patients who had received ≥8 cycles of q3w therapy to transition to q6w dosing (400 mg), based on the FDA’s approval of both dosing regimens across all indications. The primary endpoint was the 4-month disease control rate (DCR); exploratory endpoints included safety and correlative biomarkers from tissue and blood to ascertain associations between clinical response and PD-L1 expression, T-cell clonality, and immune profiling. Results: Of 43 patients (median age, 54 years; range, 34-77 years), 11 had IBC (10 with triple-negative IBC and 1 with ER+ HER2– IBC), and 32 had TNBC. The 4-month DCR was 58.1% (95% CI: 43.4%-72.9%). During a median follow-up of 11.4 months, 25 patients died. The entire cohort’s median OS and PFS times were 26.0 months (95% CI: 11.0-33.5 months) and 4.8 months (95% CI: 3.0-7.1 months), respectively. The median OS times of the IBC and TNBC groups did not differ significantly, nor did those of the CR, PR, and SD groups. The median PFS times of the IBC group (2.2 months) and TNBC group (4.8 months) did not differ significantly (p = .12), but those of the CR, PR, and SD groups did (not reached, 10.3 months, and 3.4 months, respectively; p = .01). Among the 37 patients who are off study treatment, most patients (84%; n=31/37) discontinued treatment owing to disease progression rather than toxicities (n=2), and the toxicities overall were consistent with the known profile of single-agent anti-PD1. Five patients had grade 3 events; there were no grade 4 or 5 events. Three patients had irreversible endocrinopathies (thyroiditis and adrenal insufficiency) requiring hormone replacement, but only 1 patient discontinued pembrolizumab because of these events. One patient discontinued treatment because of optic neuritis requiring steroids. Four patients completed 2 years of treatment without disease progression. Conclusions: Pembrolizumab maintenance therapy achieves acceptable disease control after induction chemotherapy. The PFS in this trial compares favorably to the expected durations of response to later lines of therapy. The toxicity profile of pembrolizumab compares favorably with those of chemotherapy and ADCs, which may provide a rationale for the use of ICIs in this setting. However, whether pembrolizumab maintenance therapy is helpful in TNBC patients who have received concurrent pembrolizumab with neoadjuvant chemotherapy is unknown, as these patients were excluded from the trial. Acknowledgements: This trial was supported by Merck.
Citation Format: Toshiaki Iwase, Angela Alexander, Vivian Chiv, Megumi Kai, Kumiko Kida, Charla Parker, Angela N. Marx, Evan Cohen, Hui Gao, James Reuben, Xiaoping Wang, Savitri Krishnamurthy, Diane Liu, Yu Shen, David Ramirez, Debu Tripathy, Daniel Booser, Clinton Yam, Vicente Valero, Bora Lim, Naoto T. Ueno, Jie S. Willey. Phase II study of Pembrolizumab Maintenance treatment in patients with HER2-negative inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) after response to chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-02-04.