Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study

Author(s): Antoinette R. Tan;Gail S. Wright; Anu R. Thummala; Michael A. Danso; Lazar Popovic; Timothy J. Pluard; Hyo S. Han; Željko Vojnović; Nikola Vasev; Ling Ma; Donald A. Richards; Sharon T. Wilks; Dušan Milenković; Jie Xiao; Jessica Sorrentino; Janet Horton; Joyce O’Shaughnessy

Source: Clin Cancer Res (2022) 28 (4): 629–636. doi.org/10.1158/1078-0432.CCR-21-2272

Gail Lynn Shaw Wright, MD, FACP, FCCP is co-author of this study that examines the efficacy of administering Trilaciclib prior to chemotherapy in patients with metastatic triple-negative breast cancer.

PURPOSE

We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716).

PATIENTS AND METHODS

Patients were randomized (1:1:1) to group 1 [GCb (days 1, 8); n = 34], group 2 [trilaciclib prior to GCb (days 1, 8); n = 33], or group 3 [trilaciclib (days 1, 8) and trilaciclib prior to GCb (days 2, 9); n = 35]. Subgroup analyses were performed according to CDK4/6 dependence, level of programmed death-ligand 1 (PD-L1) expression, and RNA-based immune signatures using proportional hazards regression. T-cell receptor (TCR) β CDR3 regions were amplified and sequenced to identify, quantify, and compare the abundance of each unique TCRβ CDR3 at baseline and on treatment.

RESULTS

Median overall survival (OS) was 12.6 months in group 1, not reached in group 2 (HR = 0.31; P = 0.0016), 17.8 months in group 3 (HR = 0.40; P = 0.0004), and 19.8 months in groups 2 and 3 combined (HR = 0.37; P < 0.0001). Efficacy outcomes were comparable regardless of cancer CDK4/6 dependence status and immune signatures. Administering trilaciclib prior to GCb prolonged OS irrespective of PD-L1 status but had greater benefit in the PD-L1–positive population. T-cell activation was enhanced in patients receiving trilaciclib.

CONCLUSIONS

Administering trilaciclib prior to GCb enhanced antitumor efficacy, with significant improvements in OS. Efficacy outcomes in immunologic subgroups and enhancements in T-cell activation suggest these improvements may be mediated via immunologic mechanisms.

Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer

ASCENT-03 shows that in first-line, PD-1/PD-L1–ineligible advanced TNBC, sacituzumab improves PFS to 9.7 vs 6.9 months and extends median duration of response (DOR) to 12.2 vs 7.2 months, with similar overall response rate (ORR) (48% vs 46%) and immature overall survival (OS) (21.5 vs 20.2 months) Grade ≥3. Adverse events (AEs) were comparable (66% vs 62%), but sacituzumab had more neutropenia and diarrhea, fewer discontinuations (4% vs 12%), and early-cycle infection-related deaths in patients without primary G-CSF. For PD-1/PD-L1–ineligible mTNBC, SG offers more durable control than chemo with manageable myelosuppression — so consider SG first-line and start G-CSF early in higher-risk patients.

Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline

Guidelines for post-mastectomy radiation include patients who received neoadjuvant therapy, with or without residual disease after treatment. A good topic to review.

First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer

Our site participated in this study, where patients were tested for ESR1 mutations via circulating tumor DNA (ctDNA). Those who tested positive were switched to camizestrant (Cami), which demonstrated improved progression-free survival.

Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly utilizes the ubiquitin–proteasome system. It was compared to fulvestrant in patients who had received one prior line of hormonal therapy with a CDK4/6 inhibitor. Among patients with ESR1 mutations, Vepdegestrant demonstrated a median progression-free survival (PFS) of 5.0 months versus 2.1 months with fulvestrant. In the overall population, the median PFS was 3.8 months for Vepdegestrant and 3.6 months for fulvestrant, indicating that the drug showed particular efficacy in tumors harboring ESR1 mutations.

Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer

Elinzanitant, a neurokinin-targeted therapy, has been shown to reduce vasomotor symptoms compared to placebo. These symptoms are one of the reasons some of my patients discontinue aromatase inhibitor (AI) therapy, so Elinzanitant presents a promising alternative to help manage these side effects. Additionally, Fezolinetant is already approved and available on the market.