Trilaciclib Advances in First-Line TNBC Treatment

3d rendered medically accurate illustration of a breast cancer: © SciePro - stock.adobe.com

The phase 3 PRESERVE 2 trial (NCT04799249) of trilaciclib (Cosela) in combination with gemcitabine and carboplatin for the first-line treatment of metastatic triple-negative breast cancer (TNBC) has been recommended to continue to the final analysis by the independent data monitoring committee, according to G1 Therapeutics, Inc.¹

No concerns regarding safety were expressed by the data monitoring committee nor did they recommend any other changes to the study. G1 continues to maintain data blinding as the interim analysis of the phase 3 study did not meet early stopping criteria.

In the final analysis, overall survival (OS) will be evaluated in the intent-to-treat population. This analysis is expected to take place in the third quarter of 2024.

“We remain confident in the ability of trilaciclib to ultimately achieve the OS primary end point based on the robust survival benefit demonstrated in the prior randomized phase 2 study, which continued to meaningfully increase over time as patients received subsequent therapies, as well as the increased statistical power for the final analysis of this pivotal study,” said Jack Bailey, chief executive officer at G1 Therapeutics, in a press release.

According to findings from a post hoc analysis from the phase 2 trial presented during a poster session at the 2023 San Antonio Breast Cancer Symposium, patients given subsequent anticancer therapy had a median OS rate of 32.7 months (95% CI, 15.3-not estimable [NE]) in the trilaciclib plus gemcitabine/carboplatin arm vs 12.8 months (95% CI, 8.3-17.8) in the placebo arm (P = .001).²

Finding showed that the median OS and progression-free survival (PFS) rates were improved in the trilaciclib arm regardless of the type of subsequent anticancer treatment that patients received. In the trilaciclib arm, the median OS from initiation of subsequent anticancer treatment was 14.0 months (95% CI, 9.0-NE) compared with 5.8 months (95% CI, 4.8-7.2) in patients who received prior gemcitabine/carboplatin only.

“While a positive interim analysis would have enabled us to bring this therapy to patients in need sooner, we look forward to completing the study and potentially making this meaningful new treatment option available to patients with this highly aggressive form of breast cancer as early as next year,” added Bailey in a press release.¹

Trilaciclib is a transient CDK4/6 inhibitor given to patients via intravenous (IV) infusion. The first-in-class therapy aims to preserve bone marrow and immune system function during cytotoxic therapy to improve patient outcomes.

In the global, multicenter, randomized, placebo-controlled, line extension PRESERVE 2 study is a phase 3 trial evaluating trilaciclib vs placebo administered prior to gemcitabine and carboplatin as a treatment for patients with locally advanced unresectable or metastatic TNBC.³

Two separate cohorts are being evaluated in the trial, both following the same general study conduct and design. Cohort 1 consists of patients who are receiving first-line therapy, regardless of PD-L1 status, who are PD-1/PD-L1 inhibitor therapy-naive. In cohort 2, patients with PD-L1-positive disease who are receiving second-line therapy following prior PD-1/PD-L1 inhibitor therapy in the locally advanced unresectable/metastatic setting are included.

Patients aged 18 years and older with evaluable locally advanced unresectable or metastatic TNBC who have available archival tumor tissue, an ECOG performance status of 0 or 1, and adequate organ function as demonstrated by normal laboratory values are included in the study. Radiation therapy for metastatic disease is also permitted.

Once enrolled, patients were randomly assigned in a 1:1 fashion to receive either trilaciclib or placebo administered before first-line gemcitabine and carboplatin via IV infusion on days 1 and 8 in 21-day cycles. Patients continued to receive treatment until disease progression.

The effect of trilaciclib vs placebo on OS in patients receiving first-line gemcitabine and carboplatin is the primary end point of the study. The secondary end points are quality-of-life and effects on chemotherapy-induced fatigue, myeloprotective effects, and PFS.

REFERENCES:

1. G1 Therapeutics to continue pivotal phase 3 trial of trilaciclib in metastatic triple negative breast cancer following interim analysis by independent data monitoring committee. News release. G1 Therapeutics, Inc. February 12, 2024. Accessed February 20, 2024. http://tinyurl.com/eakz9zdw

2. Goel S, O’Shaughnessy J, Lu K, et al. Patients with metastatic triple-negative breast cancer who receive trilaciclib prior to cytotoxic chemotherapy exhibit improved overall survival after receiving subsequent anticancer therapy. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract P02-06-12.

3. Trilaciclib, a CDK 4/6 inhibitor, in patients receiving gemcitabine and carboplatin for metastatic triple-negative breast cancer (TNBC) (PRESERVE 2). ClinicalTrials.gov. Updated January 16, 2024. Accessed February 20, 2024. https://clinicaltrials.gov/ct2/show/NCT04799249