According to results from the phase 3 AFT-38 PATINA trial, the addition of palbociclib to anti-HER2 therapy and endocrine therapy demonstrated a statistically significant improvement of progression-free survival among patients with hormone receptor (HR)-positive, HER2-positive advanced breast cancer in the first-line metastatic setting.

These results were first presented by Otto Metzger, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2024 San Antonio Breast Cancer Symposium.

While “anti-HER2 therapies have significantly improved survival outcomes,” Dr Metzger stated in his presentation, “resistance to therapy remains inevitable in advanced HER2-positive breast cancer.” He went on to explain that there is “strong rationale for blocking CDK4/6 in HER2-positive disease” as “combined CDK4/6 and HER2 inhibition shows synergistic anti-tumor activity in preclinical models of HER2-positive breast cancer.”

This open-label, phase 3 trial enrolled 518 patients with HR-positive, HER2-positive metastatic breast cancer who had no prior treatment in the advanced setting aside from induction therapy. All patients received 6 to 8 cycles of trastuzumab-based chemotherapy. Following completion of induction therapy, patients were required to have no evidence of disease progression. Patients were then randomized on a 1-to-1 basis to receive either anti-HER2 therapy and endocrine therapy alone (control arm, n = 257; prior to receiving treatment 9 patients withdrew and were not included in the safety analysis), or with the addition of palbociclib (palbociclib arm, n = 261). Patients were stratified based on pertuzumab use (97.3% of the overall population received pertuzumab), prior anti-HER2 therapy in the neo/adjuvant setting, response to induction therapy (complete response [CR], partial response [PR], or stable disease [SD]) as determined by investigator assessment, and the type of endocrine therapy administered (fulvestrant or aromatase inhibitor). The primary end point of this study was investigator-assessed progression-free survival (PFS), with overall survival (OS) as the key secondary objective.

With a median follow-up of 52.6 months, the PFS in the pertuzumab arm was 44.3 months compared with 29.1 months in the control arm, with a 26% reduction of risk of experiencing a PFS event (P = .0074). When evaluating PFS by the stratification factors, Dr Metzger stated “the magnitude of treatment benefit is maintained” by patients who received prior anti-HER2 therapy and those achieved a better response (CR or PR vs SD) to the induction phase. The confirmed objective response rate in the palbociclib arm was 29.9% vs 22.2% in the control arm (P = .046). Of the response rate, Dr Metzger noted that it was “evaluated from the time of randomization, after patients have already had [induction chemotherapy] and a 68% response rate. This is an additional response.” The clinical benefit rate was 89.3% and 81.3%, respectively (P = .01). The overall survival data was immature at the time of analysis; however, the median OS in the palbociclib arm has not been reached and the OS in the control arm is 77 months.

Neutropenia, fatigue, stomatitis, and diarrhea were among the adverse events more common in the palbociclib arm vs the control arm, with grade 3 neutropenia as the most common. Dr Metzger noted “the incidence of adverse events grade 4 or higher were similar across the study arms,” occurring in 12.3% of patients in the palbociclib arm and 8.9% of patients in the control arm (P = .21). In the palbociclib arm 7.5% of patients discontinued treatment due to adverse events. There were not treatment-related deaths reported in the study.

Dr Metzger concluded these results “reinforce the strong scientific rationale for overcoming resistance to anti-HER2 therapy and endocrine therapy with the addition of palbociclib.” He went on to say that the addition of palbociclib to anti-HER2 therapy and endocrine therapy “demonstrates a clinically meaningful improvement in PFS…more than a year of improvement” for this patient population, and this regimen “may represent a new standard of care for patients diagnosed with HR-positive, HER2-positive advanced breast cancer.”

Source:

Metzger O, Mandrekar S, DeMichele A, et al. AFT-38 PATINA: A Randomized, open-label, phase III trial to evaluate the efficacy and safety of palbociclib + anti-HER2 therapy + endocrine therapy vs anti-HER2 therapy +endocrine therapy after induction treatment for hormone receptor positive (HR+)/HER2-positive metastatic breast cancer. Presented at the 2024 San Antonio Breast Cancer Symposium. Dec 10-13, 2024; San Antonio, TX. Abstract GS2-12.