TRASTUZUMAB FOR 9 WEEKS NOT ENOUGH

Several trials have looked at a shorter duration of therapy with trastuzumab (Herceptin, Roche) for HER2+ breast cancer to reduce cardiotoxicity associated with the drug.

The Italian Short-HER study explored a 9-week course of trastuzumab combined with chemotherapy in the adjuvant setting compared with standard 1-year treatment, and as reported previously, overall failed to meet the primary endpoint of noninferiority.

Now researchers have reported a further exploratory analysis which shows that the shorter 9-week course of trastuzumab provides the same disease-free survival (DFS) as the standard 1-year course of treatment for women with low- and intermediate-risk HER+ early stage breast cancer and was associated with less cardiotoxicity.  

However, for high-risk women DFS was worse with the shorter treatment time.

The researchers conclude that the benefit–risk ratio is clearly in favor of 1-year trastuzumab for patients with high-risk disease.

"For patients at low to intermediate risk for relapse, the issue of treatment de-escalation is still an open one based on the DFS," they concluded in a poster presentation (191P) here at the European Society for Medical Oncology (ESMO) 2018 Congress.

However, breast cancer experts emphasize that 1 year of trastuzumab remains the current standard of care.  

"There is no patient for whom I would try 9 weeks of trastuzumab," ESMO expert Carmen Criscitiello, MD, PhD, of the European Institute of Oncology, Milan, Italy, told Medscape Medical News.

Details of the Short-HER Study

The phase 3 Italian Short-HER study randomized 1254 patients to receive de-escalation therapy of a shorter 9-week course of trastuzumab (short group) or standard 1-year course (long group).

The study did not meet its primary endpoint of noninferiority for the shorter 9-week course. At a median 6 years of follow-up, the hazard ratio (HR) for DFS was 1.13 (90% CI, 0.89 - 1.42), as previously reported.

For the current analysis, patients at low-, intermediate-, or high-risk were defined as follows:

• Low risk (n = 467): Tumors ≤ 2 cm and node-negative disease (N0).
• Intermediate risk (n = 586): Tumors ≤ 2 cm and 0-3 positive lymph nodes, or tumors > 2 cm and 0-3 positive lymph nodes.
• High risk (n = 191): Tumors of any size but more than 4 positive lymph nodes.

For the low-risk group, 5-year DFS was 91% for the long group and 92% for the short group (HR, 0.96; 95% CI, 0.56 - 1.66). For the intermediate-risk group, corresponding 5-year DFS was 87% and 88% (95% CI, 0.56 - 1.36). But for the high-risk group, 5-year DFS was 82% for the long group and 64% for the short group (HR, 1.99; 95% CI, 1.18 - 3.36).