Researchers confirmed the efficacy of pertuzumab plus trastuzumab as a chemotherapy-free first-line treatment option for patients with HER2-positive metastatic breast cancer, according to results from a secondary analysis of a randomized trial in JAMA Oncology. 

However, they found that use of the 50-gene prediction analysis of microarray (PAM50) predictive microarray signature did not adequately identify patients more likely to benefit from treatment with pertuzumab plus trastuzumab. 

In the phase 2 study, 210 patients were randomly assigned to intravenous pertuzumab (840 mg initial dose, then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg initial dose, then 6 mg/kg every 3 weeks) without chemotherapy (Group A) or pertuzumab-trastuzumab (with same dosage) combined with either paclitaxel or vinorelbine tartrate (Group B). Second-line therapy with trastuzumab plus emtansine was recommended for patients in both treatment groups after progression. 

Overall survival (OS) at 24 months served as the study’s primary endpoint. The researchers observed similar OS outcomes in both treatment groups, with a 24-month OS of 79% (90% CI, 71.4-85.4) for patients in Group A and 78.1% (90% CI, 70.4-85.4) for patients in Group B. With a median follow-up of 63 months (range, 2-83), the median OS was 60.5 months for patients in Group A and 68.8 months for patients in Group B. 

The median progression-free survival (PFS) during first-line treatment was 8.4 months (95% CI, 7.9-12) for patients in Group A and 23.3 months (95% CI, 18.9-33.1) for patients in Group B. The median PFS for second-line treatment—during which patients received trastuzumab plus emtansine, regardless of initial assignment—was 8.9 months (95% CI, 4.4-11.7) for patients in Group A and 6.4 months (95% CI, 4-12.7) for patients in Group B. 

Samples from 141 tumors were available for PAM50 testing using the NanoString Breast Cancer 360 assay. Although the researchers initially hypothesized that patients with HER2-enriched tumors would respond more robustly to treatment with pertuzumab plus trastuzumab, they observed no significant differences in OS or PFS between patients with or without HER2-enriched tumors. 

The chemotherapy-free treatment combination was generally associated with fewer adverse events when compared to the addition of chemotherapy. The researchers noted that only fever and allergic reactions were more common among patients treated with pertuzumab plus trastuzumab alone. 

Self-reported quality-of-life data showed that patients in Group A experienced minor initial improvements after beginning treatment, which the researchers maintained throughout the treatment period. Patients in Group B maintained stable scores throughout the treatment period. 

“The findings of this secondary analysis of a randomized clinical trial suggest that selected de-escalation with pertuzumab plus trastuzumab alone without chemotherapy as first-line treatment followed by trastuzumab plus emtansine at progression in ERBB2-positive MBC may be a reasonable treatment option for some patients.”

- Jens Huober, MD, a gynecological and obstetric specialist at Cantonal Hospital St. Gallen, Switzerland.

Reference:

https://jamanetwork.com/journals/jamaoncology/article-abstract/2808225?resultClick=1

Disclosures: Some authors declared financial ties to drugmakers. See full study for details. The study was supported by Roche.

Photo Credit: Getty Images.

By Cameron Kelsall, MD /alert Contributor