CHICAGO—Palbociclib alone and in combination with endocrine therapy offers clinical benefit among women with HR-positive, HER2-negative metastatic breast cancer; the cyclin-dependent kinase (CDK)4 and CDK6 inhibitor might reverse endocrine therapy resistance, according to findings from the Italian phase II, multicenter, open-label To Reverse Endocrine Resistance (TREnd) clinical trial (abstract 1002), presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6.
“Despite no difference being seen in clinical benefit rate [CBR], the progression-free survival [PFS] and related subgroup analyses by duration of prior endocrine therapy suggest that palbociclib could reverse acquired resistance to the same endocrine agent used in the prior line of endocrine therapy,” said lead study author Luca Malorni, MD, of the Hospital of Prato, Instituto Toscano Tumori in Prato, Italy.
The research team enrolled 115 postmenopausal patients diagnosed with HR-positive, HER2-negative metastatic breast cancer whose disease had progressed after 1 or 2 endocrine treatments, randomizing participants to receive palbociclib (125 mg daily for 3 weeks followed by 1 week off) either alone (n = 58) or in combination with their current endocrine therapy (aromatase inhibitor or fulvestrant) (n = 57). The primary study endpoint, CBR, is composed of complete response (CR), partial response (PR), and stable disease rates for at least 6 months.
CBR was similar in both groups: 54% in the combined-treatment group compared with 60% in the palbociclib monotherapy group. No study participants experienced CR; 10% of the combined-therapy group and 7% of the monotherapy group experienced PR, Malorni reported.
The difference in PFS for the two study arms did not reach statistical significance (10.8 vs 6.5 months; hazard ratio [HR], 0.69; 95% CI, 0.4–1.1; P = .12, n.s.).
However, duration of clinical benefit was significantly longer for the combination therapy group when prior endocrine therapy had concluded more than 6 months prior to study participation (median PFS, 11.5 vs 6.5 months for palbociclib alone; HR, 0.35; 95% CI, 0.18–0.7; P = .02).
Adverse events were comparable overall between the palbociclib monotherapy and combination therapy groups. Neutropenia and leukopenia were the most frequent grade 3 and grade 4 adverse events. For neutropenia, the grade 4 rates for the combination treatment group and palbociclib-only group were 11% and 19%; grade 4 leukopenia occurred in 4% and 2% of patients, respectively. Treatment was discontinued for toxicities in 4 patients in the combination therapy group and 3 patients in the palbociclib-only group.
“Translational studies are ongoing to explore potential biomarkers,” Malorni noted.