San Antonio: Results of Breast Cancer Treatment with Combination of Pertuzumab, Trastuzumab, and AI After 6 Years

Extension of PFS with combination of pertuzumab + trastuzumab + AI

The fact that adding pertuzumab to trastuzumab and chemotherapy (CHT), specifically docetaxel, in the first line can significantly improve progression-free survival (PFS) and overall survival (OS) in patients with HER2-positive metastatic breast cancer was demonstrated by the CLEOPATRA study.

PERTAIN was the first randomized phase II study to evaluate the addition of pertuzumab to trastuzumab and an aromatase inhibitor (AI) with or without induction CHT in the first line of treatment in patients with HER2⁺ and HR⁺ metastatic or locally advanced breast cancer. It showed that this approach could extend PFS (primary endpoint) in advanced HER2⁺ and HR⁺ breast cancer.

During the SABCS 2020 conference, the results of the assessment of the efficacy and safety of the combination of pertuzumab + trastuzumab + AI after a median follow-up period of 6 years were presented.

Study course

The study population was recruited from 71 sites in 8 countries from February 2012 to October 2014. It consisted of two arms in a 1:1 ratio, each with 129 participants, one receiving the combination of pertuzumab + trastuzumab + AI and the other trastuzumab + AI.

Pertuzumab was given initially at a dose of 840 mg i.v. and then 420 mg i.v. every 3 weeks, trastuzumab initially at a dose of 8 mg/kg i.v. and then 6 mg/kg i.v. every 3 weeks, and AI was chosen as anastrozole (1 mg daily p.o.) or letrozole (2.5 mg daily p.o.). Induction CHT (docetaxel or paclitaxel) could be administered for 18−24 weeks before starting endocrine therapy; 75 and 71 participants, respectively, underwent it. Treatment lasted until disease progression or the occurrence of unacceptable toxicity.

Safety was assessed in 127 vs. 124 patients. Adverse events of any grade occurred at almost the same rate in both arms, with 122 individuals each (96.1 vs. 98.4%). The most common grade ≥ 3 adverse events were hypertension, diarrhea, and neutropenia.

Results of the final analysis

After completion of the study, a follow-up period with a median of more than 6 years ensued. Based on the evaluation of the data collected during this time, researchers were able to update the data on PFS, OS, and safety. They found that:

• the benefit in PFS seen in the arm receiving the combination including pertuzumab was maintained over 6 years;
• OS was similar in both arms;
• a potentially better treatment effect was observed with the addition of pertuzumab in individuals who did not receive induction CHT after randomization;
• no new safety signals were observed.

Conclusion

The authors conclude that overall, this study provides further evidence of the role of the combination of pertuzumab with trastuzumab in the first line of treatment for HER2-positive metastatic or locally advanced breast cancer and suggests that some individuals with this disease benefit from the combination of pertuzumab + trastuzumab + AI without undergoing induction chemotherapy.

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Source: Arpino G., de la Haba-Rodriguez J., Ferrero J.-M. et al. Final analysis of PERTAIN: a randomised, open-label, multicenter phase II trial assessing the efficacy and safety of first-line pertuzumab given in combination with trastuzumab plus an aromatase inhibitor in patients with HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer. Abstract PD3-02. SABCS, 2020 Dec 8−11.