Mafalda Oliveira, MD, PhD
Invited study discussant, Mafalda Oliveira, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, said the phase II G1T28-04 study was “a ‘negative’ trial with clinically ‘positive’ results: an improved toxicity profile and overall survival benefit…. Despite the statistically negative results [for the primary endpoint], I believe the data show very interesting trends.”
Aside from the “striking” improvement in overall survival, trilaciclib-treated patients tolerated treatment better. Although hematologic toxicity overall was comparable between the study arms, patients receiving trilaciclib had less grade 3 or 4 thrombocytopenia, “which often leads to dose holding,” and lower rates of anemia, “which translated into a significantly lower incidence of red blood cell transfusions,” Dr. Oliveira noted.
“Most important, however, was that exposure to chemotherapy was greater in the trilaciclib arms,” she commented. “I wonder how the results would look if the primary endpoint had been exposure to chemotherapy or number of cycles received?”
Possible Enhanced Antitumor Immunity
Dr. Oliveira acknowledged that lacking power to detect a difference in overall survival, the finding of benefit may be just a “statistical fluke.” However, she described several preclinical and clinical studies that have demonstrated direct antitumor and immune-modulating effects of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. “The findings of this study are consistent with the hypothesis of enhanced antitumor immunity with CDK4/6 inhibition,” she said.
Although the final overall analysis is pending, and there are some questions yet to be answered, “The finding of more than a 5-month gain in overall survival warrants further investigation,” Dr. Oliveira concluded. ■
DISCLOSURE: Dr. Oliveira disclosed support from or other financial relationships with AstraZeneca, Philips Healthcare, Genentech, Roche, Novartis, Immunomedics, Seattle Genetics, GlaxoSmithKline, Boehringer Ingelheim, Puma Biotechnology, Roche, Pierre-Fabre, GP Pharma, and Grünenthal.
An unanticipated result of a randomized phase II study was the improvement in overall survival achieved with the investigational CDK4/6 inhibitor trilaciclib in women with metastatic triple-negative breast cancer. The drug was not being evaluated for its anticancer effects, but rather as a means of ...