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Pertuzumab improves PFS for HER-2–positive breast cancer
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SAN ANTONIO — The addition of pertuzumab to trastuzumab plus an aromatase inhibitor was well tolerated and prolonged PFS in postmenopausal women with HER-2–positive locally advanced or metastatic breast cancer, according to results of the phase 2 PERTAIN trial presented at San Antonio Breast Cancer Symposium.
Grazia Arpino , MD, PhD, from Rimawi M Università degli Studi di Napoli Federico II in Naples, Italy, and colleagues evaluated data from 129 HER-2–positive patients with locally advanced or metastatic breast cancer who had not received prior systemic therapy other than endocrine therapy.
All patients received an 8-mg/kg loading dose of trastuzumab (Herceptin, Genentech) followed by 6-mg/kg every 3 weeks plus 1 mg daily of anastrozole or 2.5-mg letrozole. Researchers randomly assigned 129 patients to that combination alone and 129 patients to also receive an 840-mg loading dose of pertuzumab (Perjeta, Genentech) followed by 420 mg every 3 weeks. At the researcher’s discretion, induction chemotherapy could be given for 18 to 24 weeks prior to starting endocrine therapy.
The primary endpoint was PFS, stratified by induction chemotherapy and time since adjuvant hormone therapy.
In total, 32.6% of patients in the pertuzumab arm and 28.7% in the control arm underwent induction docetaxel. Another 24.8% of patients in the pertuzumab arm and 24% of patients in the control arm underwent induction paclitaxel.
The objective response rate was 63.3% (95% CI, 95% CI, 53.5-72.3) in patients who received pertuzumab and 55.7% (95% CI, 45.7-65.3) in patients who received trastuzumab plus an aromatase inhibitor, which did not reach statistical significance. The median duration of response was 27.1 months for patients who received pertuzumab compared with 15.1 months in patients who received the control (P = .02).
The median OS was not reached in either treatment group, according to the researchers.
The median PFS was 18.9 months for patients who received pertuzumab compared with 15.8 months in patients who received trastuzumab (HR = 0.65; 95% CI, 0.48-0.89).
All-grade adverse events were observed in 122 patients in each arm (pertuzumab, 96.1% vs. control, 98.4%). More than half of patients in the pertuzumab group experienced a grade 3 event (50.4%) compared with 38.7% in the control group.
The most common grade 3 or worse events included hypertension (pertuzumab, 10.2% vs. control, 11.3%), diarrhea (7.1% vs. 2.4%) and neutropenia (3.1% vs. 6.5%).
The researchers concluded: “PERTAIN met its primary endpoint: [pertuzumab, trastuzumab and aromatase inhibitor] is effective and well-tolerated, and may offer a novel treatment option for patients with HER-2–positive/hormone receptor–positive [locally advanced or metastatic breast cancer].” – by Melinda Stevens
Reference:
Arpino G, et al. Abstract S3-04. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2016; San Antonio, Texas.
Disclosure: Arpino reports consultant roles with Amgen, Celgene, Novartis and Roche; speakers bureau roles with Amgen, Celgene, GlaxoSmithKline, Novartis and Roche; and contracts with Eisai, GlaxoSmithKline, Novartis and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Andrew D. Seidman, MD
The primary endpoint of the trial was PFS, and this was an example of a trial that really met its primary endpoint. PFS went from about 16 months to 19 months in favor of dual inhibition with trastuzumab (Herceptin, Genentech) and pertuzumab (Perjeta, Genentech). This result makes me think about the dichotomy between a statistically significant P value and a trial that may actually impact practice. I think about, for example, last year’s presentation by my colleague, Maura N. Dickler, MD, who examined the role of letrozole alone or with bevacizumab (Avastin, Genentech) in postmenopausal women with HER-2–negative breast cancer. Those results, published this year in Journal of Clinical Oncology, showed a slightly bigger PFS advantage of about 4 months in a first-line metastatic setting, and that is an example of a trial that has not changed practice and likely will not change practice.
I am chairing a working group for NCI’s breast cancer steering committee, and we are critically looking at endpoints in metastatic breast cancer clinical trials to try to avoid this scenario where we have a statistically significant result, but one that might not necessarily lead to a clinically useful regimen. The notion of incremental gain in PFS that is perhaps modest but statistically significant must be filtered by a metric that captures toxicity [and] that perhaps captures logistical inconvenience to patients. We are not really addressing cost in our own analysis, but certainly that is a variable that we need to think about.
Interestingly, in the PERTAIN trial, there was a subset analysis of patients who did not lead in with a period of chemotherapy. They received aromatase inhibitor and either [trastuzumab] or [trastuzumab and pertuzumab] straight out of the box. There were a 110 such patients. Those patients actually had a bigger gain, as the improvement in PFS went from about a year to 21 months. Unfortunately, it is a small subset of a randomized phase 2 trial, [but] it certainly is provocative and warrants further exploration.
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