No-chemo regimen in HER2+ metastatic breast cancer shortens PFS with no OS impact
Omitting first-line chemotherapy for patients with metastatic HER2+ breast cancer treated with pertuzumab plus trastuzumab did not affect overall survival (OS) despite shorter progression-free survival (PFS), according to updated results of the phase II PERNETTA* trial.
“PFS was shorter but did not seem to affect OS in the long run. Omitting chemotherapy in the first line could be discussed as an option with patients who have a low-to-intermediate tumour burden,” said first author Professor Jens Huober from University Hospital Ulm in Ulm, Germany. He called for a phase III trial to provide “definitive proof that patients are not at risk of early death if they start with antibodies alone”.
Study participants were 210 patients with HER2+ metastatic breast cancer who were randomized to receive pertuzumab (420 mg Q3W after 840 mg loading dose) plus trastuzumab (6 mg/kg Q3W after 8 mg/kg loading dose) alone (median age, 59 years) or in addition to paclitaxel (90 mg/m2 on days 1, 8, and 15 every 4 weeks; n=46) or vinorelbine (30 mg/m2 on days 1 and 8 every 3 weeks; n=59; median age, 57 years). This was followed by maintenance pertuzumab plus trastuzumab until disease progression. After progression, patients received T-DM1 (trastuzumab emtansine; 3.6 mg/kg Q3W) as second-line therapy.
At 24 months, there was no difference in OS between patients who received pertuzumab plus trastuzumab alone and those who received the combination plus chemotherapy (77.1 percent vs 76.2 percent; median 46.0 months vs not reached). [ESMO Breast Cancer Congress 2019, abstract 150O_PR]
The findings did not differ between patients with ER+ (75.0 percent [pertuzumab-trastuzumab] vs 74.2 percent [pertuzumab-trastuzumab-chemo]) and ER- disease (81.1 percent vs 79.5 percent).
However, PFS was shorter among patients who received pertuzumab plus trastuzumab alone compared with those who received the combination plus chemotherapy (median, 8.4 vs 23.3 months). Again, hormone receptor status had little impact on the findings with a median PFS of 8.3 vs 23.7 months among those with ER+ disease and 8.8 vs 22.2 months among those with ER- disease.
Most treatment-related adverse events (AEs) during first-line therapy occurred more frequently among those who received pertuzumab-trastuzumab-chemotherapy compared with pertuzumab-trastuzumab alone, with the most frequent AEs being diarrhoea and fatigue (67 percent vs 46 percent [diarrhoea] and 67 percent vs 50 percent [fatigue]). Exceptions were fever and allergic reactions which occurred more frequently in pertuzumab-trastuzumab than pertuzumab-trastuzumab-chemotherapy recipients (14 percent vs 10 percent [fever] and 13 percent vs 6 percent [allergic reaction]).
“Chemotherapy was associated with more AEs and [a] higher treatment burden as indicated by patient-reported symptoms,” said study author Dr Patrik Weder from the Cantonal Hospital in St. Gallen, Switzerland. However, quality of life as determined using the Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (FBSI-16) was comparable between groups.
“The omission of chemotherapy is an option in the presence of a dual-anti-HER2-directed-therapy followed by T-DM1 without being at risk of early death,” added Weder.
“The introduction of anti-HER2 therapies has brought a huge survival benefit in early and advanced HER2+ breast cancer, thus there is now a need for reducing the intensity and side effects of the treatment administered,” said Dr Carmen Criscitiello from the European Institute of Oncology, Milan, Italy, who was not involved in the study. She highlighted the importance of identifying the patients whose survival would not be affected by omitting certain treatments.
“Here we have a PFS that is almost two times less than that achieved with chemotherapy. The short OS endpoint did not capture if denying a treatment which is demonstrated to be meaningfully most effective impacts on long-term survival. In addition, the sample size is very small to detect a difference in OS. Avoiding chemotherapy in HER2+ disease is appealing for patients and investigators, but it has to be done safely,” said Criscitiello.