Abstract PO2-06-12: Patients with metastatic triple-negative breast cancer who receive trilaciclib prior to cytotoxic chemotherapy exhibit improved survival after receiving subsequent anticancer therapy

Abstract Background In an open-label, randomized, phase 2 trial in patients (pts) with metastatic triple-negative breast cancer (mTNBC; NCT02978716), administering trilaciclib prior to gemcitabine plus carboplatin (GCb) significantly prolonged overall survival (OS; a key secondary endpoint) versus administering GCb alone (median 19.8 vs 12.6 months; hazard ratio 0.37; P < 0.0001), with a nonsignificant trend toward improved progression-free survival (median 9.0 vs 5.7 months; hazard ratio 0.62; P = 0.13; Tan et al. Clin Cancer Res. 2022). Given murine data suggesting trilaciclib may preserve the long-term function of hematopoietic stem and progenitor cells (He et al. Sci Transl Med. 2017) and improve T-cell memory (Goel et al. Nature. 2017; Lelliott et al. Cancer Discov. 2021; Heckler et al. Cancer Discov. 2021), we examined survival of pts with mTNBC who received subsequent lines of therapy after receiving GCb with or without trilaciclib. Methods In the phase 2 trial, pts with ≤ 2 prior chemotherapy regimens for locally recurrent or metastatic TNBC were randomized 1:1:1 to receive GCb on days 1 and 8, trilaciclib prior to GCb on days 1 and 8, or trilaciclib alone on days 1 and 8 and prior to GCb on days 2 and 9. The 2 trilaciclib arms were combined for this analysis. To determine if trilaciclib improved outcomes in pts who received additional therapy after GCb, a post hoc survival analysis was performed using data from pts who received any subsequent anticancer therapy (SACT). Results In the subanalysis of data from pts with mTNBC who received any SACT after the phase 2 trial, clinical characteristics such as demographics, disease variables, duration from study treatment to first SACT, and type of SACT were balanced between the trilaciclib (n = 43) and placebo (n = 20) arms. The most common SACTs were gemcitabine, capecitabine, eribulin, taxanes, checkpoint inhibitors, carboplatin, and anthracyclines. Median OS in pts who had previously received trilaciclib was 32.7 months versus 12.8 months in those who had received placebo, with increasing separation of survival curves over time. Median OS from start of first SACT was 17.4 months in the trilaciclib arms vs 5.8 months in the placebo arm. Improved survival and sustained separation of curves was also observed in pts unable to receive SACT (trilaciclib, n = 25; placebo, n = 14), although the magnitude of benefit was smaller (median 9.4 vs 5.4 months). Mechanistic in vivo murine and in vitro human studies are underway to examine the effect of trilaciclib on the generation of memory T cells. These studies will assess the preferential differentiation of specific memory T-cell subsets along with in vivo assessment of memory T-cell responses following a rechallenge. Further data will be presented to evaluate whether the enhanced generation and preservation of a memory T-cell pool is supportive of improved outcomes in pts receiving SACT. Conclusions Data from the phase 2 study suggest that pts with mTNBC who received trilaciclib prior to cytotoxic chemotherapy have prolonged survival, which is notably improved for pts who are able to receive SACT following discontinuation of trilaciclib. The survival benefit from trilaciclib extends to pts who subsequently received immune checkpoint inhibitors and/or chemotherapy, and also to those who did not receive any SACT. Improved OS in pts receiving trilaciclib may be associated with protection of hematopoietic stem and progenitor cells and formation of a memory T-cell pool, which is critical for long-term immune surveillance and in eliciting rapid recall responses. OS will be evaluated in pts with mTNBC in the ongoing phase 3 trial of trilaciclib prior to GCb (PRESERVE 2; NCT04799249) and phase 2 trial of trilaciclib prior to sacituzumab govitecan (NCT05113966). Citation Format: Shom Goel, Joyce O'Shaughnessy, Kun-Hui Lu, Andrew Beelen, Symantha Melemed, John Yi, Michael Danso, Antoinette Tan. Patients with metastatic triple-negative breast cancer who receive trilaciclib prior to cytotoxic chemotherapy exhibit improved survival after receiving subsequent anticancer therapy [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 PO2-06-12.