Dalpiciclib Plus Pyrotinib May Be a Potential Chemo-Free Treatment Option in HER2-Positive Advanced Breast Cancer

An interim analysis indicated that dalpiciclib plus pyrotinib yielded promising results in patients with HER2-positive advanced stage breast cancer.

Dalpiciclib (SHR6390) combined with pyrotinib (Irene) showed promising efficacy and could be a potential oral, chemotherapy-free regimen for patients with HER2-positive advanced breast cancer, according to preliminary findings from a single-arm phase 2 prospective study (NCT04293276).

Findings from the interim analysis indicated that a total of 28 patients experienced an objective response, translating to an objective response rate (ORR) of 70%, meeting the primary end point of the analysis. Additionally, 2.5% (n = 1) of patients treated with the combination achieved a complete response and 67.5% (n = 27) of patients achieved a partial response. During the follow-up of 7.4 months, 12 progression-free survival (PFS) events occurred; the median PFS has not yet been reached.

“[Patients with[ HER2-positive advanced breast cancer who had not received more than 1 line of systemic therapy in advanced setting were recruited. Prior CDK4/6 inhibitors and HER2 targeted [tyrosine kinase inhibitors] were not allowed,” Min Yan, MD, a medical oncologist at Sutter Health, said during a presentation on the findings at the 2021 European Society of Medical Oncology Congress.

At data cutoff, 41 patients were enrolled, 40 of whom were eligible for efficacy, with 1 having withdrawn prior to the efficacy assessment. Patients had a median age of 53 years, and 90.2% (n = 37) had an ECOG performance status of 1. Additionally, 43.9% (n = 18) were hormone receptor (HR)– positive. At the time of screening, 92.7% (n = 38) had visceral metastases, 53.7% (n = 22) had lung metastases, 41.5% had liver metastases, and 34.1% had brain metastases. Moreover, 58.5% (n = 24) of patients had 3 or more metastatic sites.

A total of 51.2% (n = 21) of patients received 1 previous line of therapy and 48.8% (n = 28) had 0 lines of prior therapy. Additionally, 68.3% (n = 28) had previously received trastuzumab (Herceptin), and 31.7% (n = 13) were trastuzumab-naïve. Moreover, 87.8% (n = 36) were not resistant to trastuzumab. Investigators also reported that 92.7% (n = 38) had received prior chemotherapy, and 29,3% (n = 12) had received prior endocrine therapy.

Patients received 125 mg of dalpiciclib daily for 3 weeks, with 1 week off, and 400 mg of pyrotinib daily during the 28-day cycles.

Enrollment on stage 2 of the study was dependent on whether 13 or more of 23 evaluable patients in stage 1 were responders.

In a subgroup analysis, patients who were HR-positive had an ORR of 55.6% (n = 10). Additionally, patients who had no prior lines of therapy had an ORR of 75.0% (n = 15) compared with 65.0% (n = 13) among those who had 1 prior line of therapy. Investigators also reported that patients who were trastuzumab resistant had an ORR of 80.0% (n = 4) compared with 76.9% (n = 10) among those who were trastuzumab-naïve and 66.7% (n = 18) among those who were treated with trastuzumab. Additionally, an ORR was reported in 84.6% (n = 11) of patients who had brain metastases vs 70.3% (n = 26) in those who with visceral metastases and 66.7% (n = 2) in those who did not have visceral metastases.

All patients experienced some form of treatment-related adverse effects (TRAEs); however, most TRAEs were tolerable. A total of 22.0% (n = 9) of patients required dose reductions, although no treatment discontinuations due to AEs were reported.

A total of 75.6% (n = 31) of patients had grade 3/4 AEs. The most common grade 3/4 AEs were neutropenia (58.5%; n = 24), leukopenia (56.1%; n = 23), and diarrhea (17.1%; n = 7).


Yan M, Niu L, Zhang M, et al. Dalpiciclib, a novel CDK4/6 inhibitor, combined with pyrotinib for HER2+ advanced breast cancer: interim results of a phase II trial. Poster presented at the 2021 European Society of Medical Oncology Congress. September 16-21, 2021. Virtual. Accessed October 5, 2021. Abstract 276P.