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PHEREXA: Benefit for Second-Line Pertuzumab Questionable



We observed an 8-month increase in median overall survival with pertuzumab, to 36.1 months. Statistical significance for overall survival cannot be claimed due to the hierarchical testing. However, the magnitude of benefit is in keeping with prior experience of pertuzumab in metastatic breast cancer.
— Ander Urruticoechea, MD

In the second-line metastatic breast cancer setting, the addition of pertuzumab (Perjeta) to trastuzumab (Herceptin)/capecitabine did not significantly improve progression-free survival, results of the phase III ­PHEREXA trial showed.1 This is the first randomized trial to evaluate the efficacy of the triplet pertuzumab/trastuzumab/capecitabine after disease progression on trastuzumab for advanced disease.

Median progression-free survival was 9.0 months with the doublet and 11.1 months with the triplet (hazard ratio [HR] = 0.82; P = .07). The findings elicited much discussion at the 2016 ASCO Annual Meeting, where they were presented by Ander Urruticoechea, MD, of the Onkologikoa Foundation, San Sebastian, Spain.

PHEREXA randomized 452 patients with HER2-positive metastatic breast cancer to trastuzumab/capecitabine or the same plus pertuzumab, after progression on trastuzumab-based therapy.

Study Details

Patients who received a prior taxane and had disease progression during or after first-line trastuzumab-based therapy were randomly assigned to trastuzumab plus capecitabine at 1,250 mg/m2 twice daily (2 weeks on, 1 week off every 3 weeks) or pertuzumab at 840 mg, then 420 mg every 3 weeks plus trastuzumab and capecitabine at 1,000 mg/m2 every 3 weeks.

Role of Pertuzumab in Breast Cancer

  • The phase III PHEREXA trial examined the benefit of adding pertuzumab to trastuzumab/capecitabine in HER2-positive metastatic breast cancer patients progressing on trastuzumab-based therapy.
  • The study did not meet the primary endpoint of progression-free survival; median progression-free survival was 9.0 months with the doublet and 11.1 months with the triplet (HR = 0.82; P = .07).
  • Median overall survival was improved by 8 months (not statistically significant).

Median progression-free survival by independent review, the primary endpoint, was 9.0 months in the control arm and 11.1 months with trastuzumab/capecitabine/pertuzumab (HR = 0.82; P = .07). Median overall survival was 28.1 vs 36.1 months, respectively (HR = 0.68; no P value cited).

“We observed an 8-month increase in median overall survival with pertuzumab, to 36.1 months. Statistical significance for overall survival cannot be claimed due to the hierarchical testing. However, the magnitude of benefit is in keeping with prior experience of pertuzumab in metastatic breast cancer,” Dr. Urruticoechea commented.

Adverse events of grade ≥ 3 were similar for the pertuzumab arm (51.8%) and control arm (59.6%), but pertuzumab-treated patients had more grade ≥ 3 diarrhea (16% vs 10%) and left-ventricular systolic dysfunction (7% vs 3%). Treatment discontinuations due to adverse events were reported by 19.3% of the control arm and 21.1% of the pertuzumab arm. ■

Disclosure: Dr. Urruticoechea has had a consulting or advisory role with Eisai and Roche and has received reimbursement for travel, accommodations, or expenses from Eisai, Novartis, Roche, and Sysmex.

Reference

1. Urruticoechea A, Rizwanullah M, Im S, et al: PHEREXA: A phase III study of trastuzumab + capecitabine +/- pertuzumab for patients who progressed during/after one line of trastuzumab-based therapy in the HER2-positive metastatic breast cancer setting. 2016 ASCO Annual Meeting. Abstract 504. Presented June 6, 2016.


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