Adding pertuzumab to trastuzumab-AI improves PFS in HER2-positive advanced breast cancer
Adding pertuzumab to trastuzumab plus an aromatase inhibitor (AI) improves progression-free survival (PFS) in patients with HER2-positive metastatic or locally advanced breast cancer, the phase II PERTAIN study has shown.
“PERTAIN is the first randomized phase II trial to investigate pertuzumab plus trastuzumab and an AI in this patient setting,” wrote investigators of the study. “Preclinical models have suggested that HER2 blockade with pertuzumab and trastuzumab may inhibit HER2-oestrogen receptor crosstalk more efficiently, enhancing the antitumour activity of tamoxifen or oestrogen deprivation. Our study builds on these findings and those of the recently reported phase III ALTERNATIVE trial of lapatinib plus trastuzumab and an AI vs trastuzumab plus an AI alone.” [J Clin Oncol 2018;36:2826-2835]
In the open-label study, 258 patients with HER2-positive, hormone receptor-positive metastatic or locally advanced breast cancer were randomized to receive trastuzumab (8 mg/kg followed by 6 mg/kg every 3 weeks) plus an AI (oral anastrozole 1 mg every day or letrozole 2.5 mg every day) with or without pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks). Among these patients, 75 in the pertuzumab plus trastuzumab arm and 71 in the trastuzumab arm also received induction chemotherapy.
PFS, the primary endpoint of the study, was significantly improved with pertuzumab plus trastuzumab and AI vs trastuzumab plus AI alone (stratified median, 18.89 months vs 15.8 months; stratified hazard ratio [HR], 0.65; 95 percent confidence interval [CI], 0.48 to 0.89; p=0.007). The PFS improvements with the addition of pertuzumab were observed across all predefined subgroups.
Among patients who did not receive induction chemotherapy, median PFS was 21.72 months in the pertuzumab plus trastuzumab arm vs 12.45 months in the trastuzumab arm (HR, 0.55; 95 percent CI, 0.34 to 0.88). Among those who received induction chemotherapy, median PFS was 16.89 months vs 16.85 months (HR, 0.75; 95 percent CI, 0.50 to 1.13).
The objective response rate (ORR) was numerically higher with the addition of pertuzumab to trastuzumab and AI (63.3 percent vs 55.7 percent with trastuzumab and AI alone; p=0.2537), mainly driven by complete responses (7.3 percent vs 0.9 percent).
Notably, median duration of response (DoR) in patients with confirmed complete/partial response was significantly longer in the pertuzumab plus trastuzumab arm vs the trastuzumab arm (27.1 months vs 15.11 months; HR, 0.57; 95 percent CI, 0.36 to 0.91; p=0.0181).
Grade ≥3 adverse events (AEs) were reported in 50.4 percent and 38.7 percent of the patients, respectively. The most common grade ≥3 AEs were hypertension (10.2 percent vs 11.3 percent), diarrhoea (7.1 percent vs 2.4 percent), neutropenia (3.1 percent vs 6.5 percent), and anaemia (3.9 percent vs 2.4 percent).
“The superior efficacy of pertuzumab plus trastuzumab and an AI was not associated with significantly improved ORR,” the investigators noted. “The significant PFS improvements with the addition of pertuzumab may have been driven by more sustained responses, as shown by the significant increase in DoR.”
“Identifying patients who are likely to gain the most benefit from the combination of endocrine therapy with pertuzumab and trastuzumab is important as, given our results, patients with HER2-positive and hormone receptor-positive disease may not always require a chemotherapy treatment that is associated with greater toxicity,” they suggested.