The combination of palbociclib (Ibrance) and trastuzumab (Herceptin) demonstrated safety and efficacy in patients with advanced estrogen receptor (ER)+/HER2+ breast cancer, according to preliminary results of an ongoing phase II trial.
Overall, 19 of 45 patients in 3 cohorts remained progression free at 6 months with the combination, including 72% of patients with luminal-type breast cancer.
Toxicity associated with palbociclib and trastuzumab was consistent with known effects of the drugs, Eva Ciruelos, MD, of Hospital 12 de Octubre in Madrid, and colleagues reported at the San Antonio Breast Cancer Symposium.
"Identification of the nonluminal subtypes by PAM5 might help identify patients who might not derive a large benefit from the treatment strategy, regardless of hormone receptor status," the investigators concluded in a poster presentation. "Our results might have important implications for current and future clinical trials evaluating CDK4/6 inhibitors in HER2+/ER+ disease."
The combination of hormonal therapy and a CDK4/6 inhibitor has become a standard regimen in the first- and second-line setting for patients with advanced hormone receptor (HR+)/HER2-negative breast cancer. Multiple investigations are ongoing to evaluate CDK4/6 inhibitors in combination with trastuzumab in patients with HR+/HER2+ breast cancer.
Ciruelos and colleagues reported initial findings from an ongoing phase II open-label trial to evaluate the efficacy, safety, and gene expression patterns of patients treated with palbociclib and trastuzumab.
Investigators enrolled patients who had received 2 to 4 prior lines of therapy into 3 cohorts: 1 group with estrogen receptor-negative (ER-)/HER2+ breast cancer and 2 cohorts of patients with ER+/HER2+ disease. Patients with ER+/HER2+ breast cancer were randomized to receive palbociclib and trastuzumab with or without letrozole. Each cohort had a safety run-in phase of the first 12 patients (6 patients in the group randomized to letrozole, 3 patients in the other 2 groups).
The primary efficacy endpoint for all 3 cohorts was the proportion of patients who remained progression free at 6 months (PFS6). For the initial part of the trial to be considered successful, at least 6 patients had to achieve PFS6 in each cohort (5 in the ER-/HER2+ cohort, after 1 patient was inadvertently randomized to 1 of the ER+ cohorts). Secondary objectives included safety and the association of intrinsic breast cancer subtype (as determined by PAM50, N=40) with PFS.
The results showed that 5 of 15 patients in the ER-/HER2+ cohort attained PFS6 with palbociclib and trastuzumab, as did 6 of 15 patients with ER+ who received palbociclib without letrozole and 8 of 15 randomized to receive letrozole.
PAM50 results showed that 11 of 40 patients had luminal breast cancer (A and B combined, all with ER+ disease. The analysis showed that 25 of 40 patients had HER2E intrinsic subtype breast cancer (12 with ER+ tumors, 14 with HR- tumors), and 3 patients (all ER+) had normal-like tumors, and 1 (ER-) had a basal-like tumor.
Patients with luminal subtype disease had a threefold higher median PFS (12 versus 4 months). The difference existed in an analysis of all 40 patients with PAM50 results (12.4 vs 4.1 months, P
= .052) and in an analysis limited to patients with ER+ breast cancer (12.4 vs 4.1, P
= .044). The difference persisted after exclusion of patients with normal-like tumors.
An analysis of clinical benefit rate at 6 months (CBR6, response plus stable disease) also revealed significantly better results in patients with luminal type breast cancer. In the overall population and the ER+ group, 8 of 11 (72.7%) patients with luminal tumors attained CBR6. That compared with 9 of 29 (31.0%) patients with nonluminal intrinsic subtype in the total population (P
= .031) and 4 of 16 patients with ER+ breast cancer (P
The most common adverse events (all grades) in the trial were neutropenia (80%), asthenia (60%), anemia (33%), and thrombocytopenia (29%, including 53% in patients who received letrozole). The most common grade 3/4 adverse events were neutropenia (69%) and thrombocytopenia (13%).
Because all 3 cohorts met criteria for a successful outcome, enrollment will continue in an expansion component with accrual of an additional 16 patients per cohort.
Ciruelos R, Willagrasa P, Pare L, et al. SOLTI-1303 PATRICIA phase II (stage I) – pabloclib and trastuzumab in postmenopausal patients with HER2-positive metastatic breast cancer. In: Proceedings from the 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, Texas.
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