Abstract P3-09-09: Pre-operative Pembrolizumab (pembro) with Radiation Therapy (RT) in Patients with Operable Triple-Negative Breast Cancer (TNBC)

Background: Pembrolizumab (pembro)-mediated checkpoint blockade has shown modest efficacy in triple negative breast cancer (TNBC). Pathologic complete response (pCR) rates in TNBC are 34-55% with neoadjuvant chemotherapy (Cortazar Lancet 2014, Sharma Clin Cancer Res 2017) and 26% with neoadjuvant stereotactic radiation therapy (RT) alone (Riet Eur J Cancer 2017). However, because RT induces immune-mediated cell death that can generate a rich supply of tumor antigens and trigger anti-tumor immunity, the addition of pembro to RT can generate robust anti-tumor immune responses as demonstrated in metastatic TNBC (McArthur ASCO 2018). If administered in the pre-operative setting, immune therapy plus RT could induce long-term tumor-specific memory, and ultimately, improve cure rates. This study aimed to establish the safety of pre-operative pembro plus RT in 20 TNBC patients for whom lumpectomy and adjuvant RT were planned and to explore predictive biomarkers (NCT03366844). Methods: Women planning breast conserving surgery for operable, stage II/III, TNBC were enrolled in this single-institution pilot study. Study treatment consisted of pre-operative pembro (200mg IV) followed 3 weeks later by pembro (200mg IV) plus RT (24 Gy/3 fractions) to the primary breast tumor followed 3-5 weeks later by standard-of-care (SOC) neoadjuvant chemotherapy. Adjuvant RT was administered per SOC after surgery, but without a boost dose. Research blood and tumor biopsies were obtained at baseline, at week 4 prior to pembro/RT, and at week 6-8 prior to chemotherapy initiation. Co-primary endpoints were: safety/tolerability (defined by the number of patients who do not necessitate a delay in SOCchemotherapy or surgery) and change in tumor infiltrating lymphocyte (TIL) score. Secondary endpoints include safety/toxicity up to 19 weeks after study enrollment and pathologic complete response (pCR) rate. Results: As of 7/8/19, the accrual goal of 20 patients has been met. The median age is 53y (range 33-70y). The stage distribution is IIA (12), IIB (5), IIIA (2) and IIIC (1) with biopsy proven nodal involvement in 40%. To date, 18 patients have completed pembro/RT and 12 have completed chemotherapy and surgery. All patients received a taxane containing regimen, 8/12 (67%) received carboplatin and 10/12 (83%) received an anthracycline. Three patients did not complete the planned course of chemotherapy, two of whom had residual disease. None of the patients experienced significant delay (>2 weeks) in receiving SOC treatment. There were no observed grade 3 or 4 toxicities observed with pembro +/- RT. Grade 4 colitis in 1/18 was reported during SOC chemotherapy and was attributed to pembro. The most frequent grade 1/2 toxicities were nausea (3/18), arthralgia (12/18), fatigue (10/18), maculopapular rash (1/18), diarrhea (1/18) and mucositis (1/18). Of the 12 patients who completed surgery, 8/12 (67%) were ypT0N0, 9/12 (75%) were ypT0/Tis and 10/12 (83%) were ypN0. Of the 5 patients with node-positive disease at diagnosis, 3/5 (60%) became ypN0 and 1/5 (20%) became ypN1mic. Change in TILs after pembro or pembro-RT did not correlate with treatment response, however baseline TIL count ≥10% in the initial biopsy was associated with pCR (p = 0.01). Conclusions: Neoadjuvant pembro plus RT prior to SOC chemotherapy is safe/feasible and may increase pCR rates beyond chemotherapy alone. A randomized phase 2 study of checkpoint blockade +/- RT in a larger cohort is planned. Citation Format: Heather McArthur, Stephen Shiao, Scott Karlan, Farin Amersi, Brittany Arnold, Reva Basho, Michele Burnison, Alice Chung, Cathie Chung, Catherine Dang, Armando Giuliano, Negin Habibi Khameneh, Simon Knott, Cynthia Martin, Philomena McAndrew, Monica Mita, Dorothy Park, Christina Abaya, Alice Ho. Pre-operative pembrolizumab (pembro) with radiation therapy (RT) in patients with operable triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-09.