|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Extended adjuvant therapy with letrozole after sequential endocrine therapy may increase disease-free survival in post-menopausal women with breast cancer who were previously treated with tamoxifen, according to the results of a prospective, randomized, multicentric trial conducted in Italy (ClinicalTrials.gov Identifier: NCT01064635). The findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
Between August 2005 and May 2010, the authors randomly assigned 2056 patients in a 1:1 ratio to receive letrozole for 2 to 3 years (control arm), or for 5 years (extended arm). The patients were all post-menopausal women with stage I, II, or III breast cancer free of recurrence after 2 to 3 years of adjuvant tamoxifen. The investigators followed the patients for about 10 years (IQR range, 8.6-11.4). The primary end point of the study was disease-free survival.
After analyzing data from the entire intention-to-treat population of 2056 patients, the researchers found that the 10-year estimated disease-free survival was 77% in the group that received letrozole for 5 years compared with 74% in the group that received letrozole for 2 to 3 years (HR 0.84, 95% CI 0.69-1.03; P =.09). A landmark analysis of 1891 patients also showed that the 8-year estimated disease-free survival was 77% in the arm that received letrozole for 5 years compared with 72% in the control arm (HR 0.81, 95% CI 0.65-1.00; P =.051).
“In conclusion, our study showed that after 2 [to] 3 years of tamoxifen, extended adjuvant treatment with additional 5 years of letrozole is associated with a 19% reduction in invasive disease-free survival events,” said lead study author Lucia Del Mastro, MD, of the University of Genova, and Ospedale Policlinico San Martino in Genova, Italy.
However, a greater proportion of patients in the arm that received treatment for 5 years discontinued treatment early than in the control arm. Of 1026 patients in the extended arm, 43% discontinued treatment early compared with 24% of 1030 patients in the control arm. Toxicity and primary disease events were among reasons for discontinuation.
In addition, the researchers found that the burden of certain side effects was greater in the extended arm. When the investigators evaluated 1960 patients for toxicity, they found, for example, that 81 (8%) women who received letrozole for 5 years were diagnosed with osteoporosis compared with 47 (5%) women who received treatment for 2 to 3 years. Moreover, 9 (1%) women who received treatment for the longer time period experienced bone fractures compared with 5 (<1%) women who received letrozole for the shorter time period experienced bone fractures.
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Del Mastro L, Mansutti M, Bisagni G, et al. Benefit from letrozole as extended adjuvant therapy after sequential endocrine therapy: A randomized, phase III study of Gruppo Italiano Mammella (GIM). Presented at: 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 504.