Minikel, Dawn

Abstract Abstract Title: Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 Background: KEYNOTE-522 was a randomized, double-blind, placebo-controlled phase 3 trial which resulted in the FDA approval of pembrolizumab with neoadjuvant chemotherapy for patients with newly diagnosed, high-risk, early-stage triple-negative breast cancer (TNBC). Despite the significant improvement in pathological complete response (pCR) and event-free survival rates across all patients, the landmark trial included only 4.5% Black patients. It is essential to assess outcomes in representative treatment populations. We assessed real-world toxicity and treatment outcomes across Black and White patients who received standard-of-care treatment per KEYNOTE-522. Methods: In this retrospective, multicenter study, we examined patients with early-stage TNBC who received planned treatment per KEYNOTE-522 as standard-of-care (SOC) therapy. 16 sites were included in the analysis. IRB approval was obtained from each participating site. Number and length of treatment delays, treatment-related toxicities (both chemotherapy and immune-related) of all grades, and pCR rate were collected from the electronic medical record of each participating site, and deidentified data were shared for central analysis. Results: Of the 577 patients who initiated treatment with chemotherapy and immunotherapy, 534 patients were included in this analysis with 105 patients who self-identified as Black (19.7%) and 429 who self-identified as White (80.3%). There were no statistically significant differences in clinical and pathological characteristics between the two groups. White women were more likely to have grade 3+ immune-related adverse events (irAEs) compared to Black women (33.8% vs 20.9%, P=0.011). There was no significant difference across Black and White patients with respect to grade 3+ chemotherapy-related adverse events. Out of the 444 patients who have completed surgery, no difference in pCR rate was observed between Black and White women (45/86 52.3% vs 200/358 55.9%) (p = 0.6). The authors also saw no difference in the rates of hospitalizations between Black and White women (39% vs 36% p = 0.5), and rates of acute care utilization (38% vs 38% p = 0.9). Conclusions: We report safety and efficacy across Black and White women in a real-world analysis of patients who received treatment per KEYNOTE-522. Notably, White patients had a significantly higher frequency of grade 3+ irAEs, although the reason for this finding is unclear based on this analysis. Black patients had similar pCR rates and rates of treatment-related hospitalizations compared to White patients. Assessment of outcomes and toxicity by race in clinical trials and real-world analyses are critical in drug development. Citation Format: Mara Hofherr, Andrew Davis, Spenser January, Emily Owen, Farah Raheem, Lida A. Mina, Suganya Arunachalam Karikalan, Lauren Lyons, Meredith Watson Rose, Katherine Madden, Jerline Hsin, Aimee Keegan, Wai Yu, Shawna Kraft, Allison Schepers, Emily Armgardt, Douglas Mazewski, Alison Svoboda, Kayla Harwood, Jodi Taraba, Yonatan Resnick, Shelly Hummert, Lisa Grate, Sidney Keisner, Jacob Hobbs, Todd Davis, Kristin Bastian, Dawn Minikel, Wiliam Adler, Traci White, Avneek Singh Sandu, Fouad Boulbol, Kelsey Finch, Katherine Clifton. Real-world analysis comparing Black and White patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 [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 PS14-02.

Abstract Title: Real-world analysis of adverse events in patients with triple-negative breast cancer receiving therapy per KEYNOTE-522 Background: KEYNOTE-522 was a randomized, double-blind, placebo-controlled phase 3 trial which resulted in the FDA approval of pembrolizumab with neoadjuvant chemotherapy for patients (pts) with newly diagnosed, high-risk, early-stage triple-negative breast cancer (TNBC). Given the improvement in pathological complete response (pCR) and event-free survival rates, this regimen has emerged as standard-of-care (SOC) therapy. To date, real world outcome analyses are limited. Methods: In this retrospective, multicenter study, we examined pts with early-stage TNBC who received planned treatment per KEYNOTE-522 as SOC. 16 sites were included in the analysis. IRB approval was obtained from each participating site. Number and length of treatment delays, treatment related toxicities (both chemotherapy and immune-related) of all grades, and pCR rate were collected from the electronic medical record of each participating site, and deidentified data were shared for central analysis. Results: 577 pts were included in this analysis. The median age of the cohort was 52 [range 27-77]. 457 pts had T1-2 disease and 139 had T3-4 disease. 316 pts had N0 disease and 261 had N1-3 disease. 506 pts had baseline ECOG 0, 62 had ECOG 1, and 9 had ECOG 2-3. Of the 482 patients who had surgery at the time of this analysis, 219 patients had pCR (54.5%) and 192 pts were still receiving treatment. 217 patients (37%) had an adverse drug event (ADE) causing dose reductions and 228 patients (39.5%) had to discontinue treatment early. There were 360 unplanned care visits, with 91 patients having 2+ visits. 66 patients had hospitalizations due to the regimen with 102 total hospitalizations. 179 (31%) of patients had grade 3+ immune related adverse events (irAEs), including many that are rare and potentially serious. 317 (54%) had an immune related adverse effect (see Table 1). There was no significant difference in the frequency of grade 3+ irAE based on age or body mass index. We observed no difference in residual disease between patients who discontinued treatment early and those who did not. However, if patients had an ADR causing a dose reduction, pts were significantly more likely to have residual disease (P=0.039) Conclusions: In a multicenter real-world analysis, the KEYNOTE-522 regimen was associated with a high frequency of dose reductions, early treatment discontinuations, ER visits, and hospitalizations. This may have accounted for a lower pCR rate than observed in the landmark clinical trial. Most grade 3+ irAEs occurred at greater frequency in our real-world analysis. Providers should carefully monitor for toxicity to ensure optimal patient outcomes. Table 1 Citation Format: Mara Hofherr, Katherine Clifton, Spenser January, Emily Owen, Farah Raheem, Lida A. Mina, Suganya Arunachalam Karikalan, Lauren Lyons, Meredith Watson Rose, Katherine Madden, Jerline Hsin, Aimee Keegan, Wai Yu, Shawna Kraft, Allison Schepers, Emily Armgardt, Douglas Mazewski, Alison Svoboda, Kayla Harwood, Jodi Taraba, Yonatan Resnick, Shelly Hummert, Lisa Grate, Sidney Keisner, Jacob Hobbs, Todd Davis, Kristin Bastian, Dawn Minikel, Traci White, William Adler, Avneek Singh Sandu, Fouad Boulbol, Kelsey Finch, Andrew Davis. Real-World Analysis of Adverse Events in Patients with Triple Negative Breast Cancer Receiving Therapy per KEYNOTE-522 [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 PS14-06.