Without trastuzumab, women who received standard chemotherapy had a 3-year event-free survival rate of 56%. When neoadjuvant and adjuvant trastuzumab was added, survival climbed to 71% (hazard ratio, 0.59, p = 0.013).
As reported in the January 30th issue of The Lancet, Dr. Luca Gianni, from Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and colleagues assessed the outcomes of 235 women who were randomized to receive neoadjuvant chemotherapy alone or combined with 1 year of treatment with neoadjuvant and adjuvant trastuzumab.
After other studies began showing beneficial effects with adjuvant trastuzumab, subjects in the chemotherapy-only group were offered this treatment as well. Ultimately, 19 patients (16%) opted for adjuvant trastuzumab.
The neoadjuvant chemotherapy regimen included doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil. The study also featured a parallel cohort of 99 patients with HER2-negative disease; these women received the chemotherapy regimen, but not trastuzumab.
As noted, the trastuzumab group had significantly better event-free survival than did the chemotherapy-only group. Local, regional, and distant recurrences were all less common in the trastuzumab group. By contrast, overall survival at 3 years in the trastuzumab and chemotherapy-only groups was not significantly different: 87% and 79%, respectively.
No difference in event-free survival was seen between HER-positive patients not treated with trastuzumab and HER-negative patients. Event-free and overall survival rates for HER-negative patients at 3.2 years were 67% and 86%, respectively.
Adverse events were generally comparable in the three groups, there was no increase in grade 3 or 4 non-cardiac toxicities with trastuzumab. Patients given trastuzumab were less likely to maintain normal cardiac function, but the reductions in function were mostly mild.
“Adjuvant studies require thousands of women to show survival benefits, at high cost and often long follow-up,” Dr. Melanie D. Seal and Dr. Stephen K. Chia, from British Columbia Cancer Agency, Vancouver, Canada, comment in an editorial. “Studies such as NOAH illustrate the benefits and potential of neoadjuvant trials and should challenge the dogma of our current strategies of therapeutic trials in early-stage breast cancer.”
NOAH was funded by F. Hoffmann-La Roche, the maker of Herceptin.