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Expert Point of View: Cristina Saura Manich, MD, PhD


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Study discussant Cristina Saura Manich, MD, PhD, Head of the Breast Cancer Program at the Vall d’Hebron University Hospital in Barcelona, offered some thoughts as to the underlying mechanism of benefit from trilaciclib in the phase II study reported by Dr. Joyce A. O’Shaugnessy.

Trilaciclib is a first-in-class CDK4/6 reversible inhibitor that induces cell-cycle arrest in hematopoietic stem cells. It is designed to preserve bone marrow and immune system function during chemotherapy, which may, in turn, improve patient outcomes. To avoid possible concerns regarding cell-cycle arrest with chemotherapy, the investigators studied trilaciclib in a functionally CDK4/6-independent tumor in metastatic triple-negative breast cancer, Dr. Saura explained.

‘Most Striking’ Finding: Improved Survival

The “most striking” finding was the significant improvement in overall survival for the trilaciclib cohorts, with median overall survival increased from 12.6 months with gemcitabine/carboplatin to 19.8 months in the combined trilaciclib arms (P < .0001). Of note, gemcitabine/carboplatin “did not underperform, as its overall survival is in line with findings from similar trials,” she added.

Cristina Saura Manich, MD, PhD

Cristina Saura Manich, MD, PhD

“Subgroup analyses suggest that this benefit is seen regardless of CDK4/6 dependence and PD-L1 expression. Data from immune subtyping analyses and immunosequencing suggest that administering trilaciclib prior to gemcitabine/carboplatin both preserves and enhances immune system function…. A similar overall survival benefit was seen for patients with high or low immune-related expression,” Dr. Saura pointed out. Such observations point to the drug’s immunomodulatory effects, which may exert antitumor activity and “may help to explain the overall survival benefit in this trial,” she commented.

Dr. Saura noted that the trial was not powered to detect differences in overall survival. Thus, with overall survival as its primary endpoint, the registrational trial’s results will be important. 

DISCLOSURE: Dr. Saura disclosed support from or other relevant relationships with AstraZeneca, Philips Healthcare, Genentech, Roche, Novartis, Immunomedics, Seattle Genetics, GlaxoSmithKline, Boehringer Ingelheim, Puma Biotechnology, Roche, Pierre-Fabre, GP Pharma, and Grunenthal.

 


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