The addition of the monoclonal antibody pertuzumab to standard therapy (trastuzumab [Herceptin] plus the chemotherapy drug docetaxel) for women with an aggressive type of early-stage breast cancer (HER2-positive disease) improved the rate of complete tumour disappearance by more than half after just four cycles (12 weeks) of treatment compared with the standard regimen alone.
The striking findings of the phase 2 NeoSphere study, published Online First in the Lancet Oncology, also found that this combination without the addition of chemotherapy achieved tumour eradication in a sizeable proportion of women (17%) with none of the chemotherapy-associated toxicities, suggesting that it might be possible to treat some tumours without chemotherapy.
"The tumour response to this new triplet combination is one of the highest reported to date, despite just a short treatment time, and could be a big advance for women with HER-2 positive disease. Moreover, these findings suggest a potential future role for chemotherapy-free HER-2 targeted therapy, although such regimens require further investigation"*, explains lead author of the study Luca Gianni from the San Raffaele Cancer Center, Milan, Italy.
About one in five breast cancer tumours are HER-2 positive. Trastuzumab is a monoclonal antibody developed to block the cancer-causing activity of the HER2 protein and is the standard therapy for women with HER-2 positive disease. Pertuzumab is another HER-2 targeted drug that has a complementary mechanism of action to trastuzumab and has shown promising anti-tumour activity in a previous phase 2 trial of women with advanced HER-2 positive breast cancer.
The NeoSphere study was designed to compare different regimens of HER-2 targeted therapies with and without chemotherapy. The study included 417 previously untreated women with early HER-2 positive disease who were randomly assigned to receive four cycles of treatment before surgery with either: trastuzumab plus doctaxel; pertuzumab and trastuzumab plus doctaxel; trastuzumab plus pertuzumab; or pertuzumab plus docetaxel.
About 46% of women who received the new triple combination had a pathological complete response where the tumour completely disappeared, compared with 29% of women given standard therapy, and 17% given pertuzumab plus trastuzumab without chemotherapy.
Importantly, the new triple combination was well tolerated and did not significantly increase side effects or cardiac risk compared with the other regimens.
Less than 2% of women given the chemotherapy-free trastuzumab and pertuzumab regimen reported grade 3 or higher adverse events compared with 12% to 14% of women in the chemotherapy-containing treatment groups.
The authors conclude: "These findings justify further exploration in adjuvant trials and support the neoadjuvant [before surgery] approach for accelerating assessment in early breast cancer."
Professor Luca Gianni, San Raffaele Cancer Center, Milan, Italy. T) 39-02-2643-6529 E) Gianni.luca@hsr.it
Notes to Editors:
*Quote direct from author and cannot be found in text of article
Journal
The Lancet Oncology