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SAN ANTONIO -- The addition of palbociclib (Ibrance) to current standard-of-care therapy following induction chemotherapy resulted in a significant and clinically meaningful improvement in progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-positive metastatic breast cancer, the phase III PATINA study showed.

The median PFS was 44.3 months among patients treated with palbociclib in combination with anti-HER2 therapy and endocrine therapy versus 29.1 months in a control arm of patients treated with anti-HER2 therapy and endocrine therapy alone (HR 0.74, 95% CI 0.58-0.94, P=0.0074), reported Otto Metzger, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston.

The 5-year PFS rate was 43.2% in the palbociclib arm compared with 33.4% in the control arm, he noted at the San Antonio Breast Cancer Symposium (SABCS).

The overall response rates (ORR) in the palbociclib and control groups were 29.9% and 22.2%, respectively -- responses evaluated from the time of randomization after patients had achieved a best response of 68.5% with induction therapy.

Overall survival (OS) data were immature, with median OS not reached in patients randomized to palbociclib compared with 77 months in the control arm. The estimated 5-year OS rates were 74.3% and 69.8%, respectively (HR 0.86, 95% CI 0.6-1.24).

"Our results really reinforce the strong scientific rationale for overcoming resistance to anti-HER2 therapy and endocrine therapy with the addition of palbociclib," Metzger said. "The PATINA phase III study demonstrated a clinically meaningful improvement in PFS among patients diagnosed with HR-positive, HER2-positive disease. The median PFS in the control arm of our study ... far exceeds what we had expected, and despite that, we're seeing a 15.2-month improvement ... with the addition of palbociclib."

"The toxicity was manageable," he added. "And I would argue that palbociclib, when added to anti-HER2 and endocrine therapy, may represent a new standard of care for patients diagnosed with HR-positive/HER2-positive advanced breast cancer."

SABCS invited discussant Sara Hurvitz, MD, of the University of Washington and the Fred Hutch Cancer Center in Seattle, who called the PFS results in the palbociclib arm "incredible ... and really historic, I would argue."

Moreover, she noted the interim OS results were more than 6 years. "So again, this is historic and very important data," she said.

"Today, we heard definitive proof that there are benefits to targeting more than just HER2 in HER2-positive breast cancer," she added. "CDK4/6 inhibitors, in my opinion, should be considered as part of the armamentarium for our patients. Nuanced patient selection will be needed, and we need more biomarkers and patient-reported outcomes."

Metzger noted that while anti-HER2 therapies have significantly improved survival outcomes, "resistance to therapy remains inevitable in a majority of patients with advanced HER2-positive breast cancer."

However, there is a rationale for blocking CDK4/6 in HER2-positive disease, he said, adding that combined CDK4/6 and HER2 inhibition has been shown to be synergistic and have anti-tumor activity in preclinical models of HER2-positive breast cancer.

For the trial, the researchers enrolled 518 patients in eight countries from June 2017 to July 2021. These patients were randomized to receive palbociclib plus anti-HER2 therapy consisting of trastuzumab (Herceptin) or trastuzumab plus pertuzumab (Perjeta) and endocrine therapy or anti-HER2 and endocrine therapy alone.

Median patient age was 53 years, over 90% were white, and the median number of cycles of induction therapy prior to randomization was six.

More than 97% of patients were treated with dual (trastuzumab and pertuzumab) HER2 blockade, and about 90% of patients were treated with an aromatase inhibitor.

Neutropenia was the most common grade 3 event, occurring in 63.2% of patients in the palbociclib arm, "which we believe to be consistent with what we know from the toxicity profile of palbociclib," Metzger reported.

In addition, diarrhea was more common in the palbociclib arm, with grade 2 and grade 3 diarrhea occurring in 26.4% and 11.1% of patients, respectively, versus 10.5% and 1.6% in the control arm.

"Importantly, the incidence of grade ≥4 adverse events was similar across the study arms [12.3% in the palbociclib arm vs 8.9% in the control arm]," Metzger noted. Treatment discontinuations due to adverse events occurred in 7.5% of patients in the palbociclib arm, and there were no reported treatment-related deaths in either arm.

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