In an observational study conducted in Germany that began after the marketing authorization was received for reference trastuzumab in early breast cancer (EBC), researchers were able to analyze outcomes for patients treated with trastuzumab both with and without cytotoxic treatment.
Trastuzumab (Herceptin) is a monoclonal antibody that has been used in adjuvant treatment of HER2-positive early breast cancer (EBC) for over 10 years. Based on results from previous randomized trials, combined treatment with trastuzumab and chemotherapy (either as primary systemic or adjuvant treatment) is considered the standard of care in this type of cancer.
In an observational study conducted in Germany that began after the marketing authorization was received for reference trastuzumab treatment in early breast cancer, researchers were able to analyze outcomes for patients treated with trastuzumab both with and without cytotoxic treatment.
Results of the study found that trastuzumab plus chemotherapy should remain the preferred treatment option in all patients with HER2-positive EBC with an indication for adjuvant treatment. The study also reported, however, that a limited number of patients will need an alternative treatment approach, due either to contraindications or patient preference (in an American interview-based regional survey of 119 women who did not receive guideline-recommended adjuvant therapy, patient refusal was the reported reason for 31% of cases). In this specific subgroup of patients, trastuzumab monotherapy, eventually combined with endocrine agents, could be a reasonable option that offers beneficial long-term outcomes.
Between September 2006 and July 2011, 3940 patients (n = 3940) with HER2-positive breast cancer were recruited for participation in the study. Patients were then categorized as 3935 with (n = 3703; 94%) or without (n = 232; 6%) any sequential or concurrent (neo)adjuvant chemotherapy.
Relapse-free survival (RFS) and overall survival (OS) were calculated as the time between the baseline assessment before the first trastuzumab administration and the respective event. Surviving patients (without relapse for RFS) were censored at the last valid observation point. Patients who were not receiving chemotherapy were almost 3 years older on average (P = .0008), and were often presented with a worse performance status (P <.0001) than those receiving chemotherapy.
A total of 452 RFS events were observed by the authors. In the chemotherapy group, the RFS rate was 90% (95% CI, 89%-92%) at 3 years and 83% (95% CI, 81%-85%) at 5 years. The corresponding rates were distinctly lower in the cohort receiving no chemotherapy: 84% (95% CI, 78%-89%) and 80% (95% CI, 74%-87%), respectively.
The authors noted that the difference between treatment groups was statistically significant (HR 1.49; 95% CI, 1.06-2.09; P =.022). A similar pattern was observed for OS, although with only marginally non-significant inferiority for the group receiving no chemotherapy, based on a total of 248 reported deaths (HR 1.56; 95% CI, 1.00-2.44; P =.052).
In order to better assess the utility of trastuzumab as monotherapy, the authors say that they can compare their results against patients with HER2-positive breast cancer who did not receive adjuvant chemotherapy or trastuzumab, and cite a large cohort of 965 patients with small breast cancer tumors from the MD Anderson Center who had a 5-year RFS rate of 77%. “Indirect comparisons (with the usual caveats) against our RFS estimate of 80% suggest considerable benefit from trastuzumab monotherapy,” write the authors.
These data, write the authors, support the use of trastuzumab plus chemotherapy as the preferred treatment in patients with HER2-positive EBC and an indication for adjuvant treatment, though trastuzumab monotherapy combined with endocrine therapy might be a reasonable option offering favorable outcomes in some patients.