Abstract GS4-01: Ten-year results from NRG Oncology/NSABP B-42: A randomized, double-blinded, placebo-controlled clinical trial of extended adjuvant endocrine therapy with letrozole (L) in postmenopausal women with hormone-receptor+ breast cancer (BC) who have completed previous adjuvant therapy with an aromatase inhibitor (AI)
Authors: Mamounas Eleftherios P , Bandos Hanna , Lembersky Barry C , Jeong Jeon Hyeon , Geyer Charles E , Rastogi Priya , Fehrenbacher Louis , Graham Mark L , Chia Stephen K , Brufsky Adam M , Walshe Janice M , Soori Gamini S , Dakhil Shaker R , Seay Thomas E , Wade James L , McCarron Edward C , Paik Soonmyung , Swain Sandra M , Wickerham D Lawerence , Wolmark Norman 
Published: March 2020

Background: In the NSABP B-42 trial we aimed to determine whether 5 yrs of letrozole (L) v placebo (P) improves DFS in patients (pts) who have completed 5 yrs of hormonal therapy (tx). 3966 postmenopausal pts with stage I-III, hormone-receptor+ BC, disease-free after 5 yrs of an AI or tamoxifen (TAM) for ≤3 years → AI for the remainder of 5 yrs, were randomized to L 2.5 mg or P daily for an additional 5 yrs. In the primary analyses the beneficial effect of extended tx with 5 yrs of L did not reach statistical significance on disease-free survival (DFS). There was no significant improvement in overall survival (OS) with L, but L did provide a significant improvement in breast-cancer-free interval (BCFI) and distant recurrence (DR). The updated results based on the data received as of April 30, 2019, are presented here. Methods: Stratification was by pathological nodal status, prior adjuvant TAM or not, and baseline dexa T scores (&gt;-2.0, ≤-2.0 SD). Primary endpoint was DFS including local, regional, distant recurrence, second primary cancers, and deaths from any cause as first event. Secondary endpoints included OS, BCFI (including recurrence or contralateral BC as first event), DR, osteoporotic fractures (OF), and arterial thrombotic (AT) events. Differences in DFS, OS, BCFI, DR, OF, and AT between L and P were assessed by the stratified log-rank tests and Cox proportional hazards models. Statistical significance level was set at 0.05. Results: Median follow-up for 3923 pts included in the current analyses was 9.3 yrs. As of 4/30/19, 890 DFS events had occurred (L=411, P=479); L resulted in a statistically significant increase in DFS v P (HR=0.84; 95% CI 0.74, 0.96; p=0.011); 10-yr DFS was L=76.1% and P=72.1%. The effect of L was statistically significantly different for pts with baseline T score ≤-2.0 (HR=0.63; 95% CI 0.49, 0.82) v those with a score &gt;-2.0 (HR=0.93; 95% CI 0.80, 1.09) (interaction p=0.013). 495 deaths occurred (L=243, P=252); there was no statistically significant difference in OS with L v P (HR=0.97, 95% CI 0.82, 1.16; p=0.77); 10-yr OS was L=86.1% and P=85.5%. 413 BCFI events occurred (L=178, P=235); L v P resulted in a statistically significant 26% decrease in BCFI events (HR=0.74, 95% CI 0.61, 0.91; p=0.003); 10-yr cumulative incidence (Cum In) of BCFI was L=10.3% v P=13.3%. 229 DRs occurred (L=96, P=133); L v P resulted in a statistically significant 29% reduction in DR (HR=0.71, 95% CI 0.55, 0.93; p=0.01); 10-yr Cum In of DR was L=5.7% v P=7.5%. There were 209 OF (L=109, P=100). There were no significant differences in time to OF with L v P (P=0.46). Cum In of OF through 10 yrs was L=6.5% v P=6.4%. There were 154 AT events (L=82, P=72). Treatment with L did not result in an overall statistically significant increase in AT events compared to P (p=0.38). Cum In of AT through 10 yrs was L=4.7% v P=4.1%. Conclusions: The effect of extended tx with 5 yrs of L on DFS persisted in the updated analyses and reached statistical significance. There was no significant improvement in OS with L, but L continued to provide a significant improvement in BCFI and DR. Support: U10CA180868, -180822; UG1CA189867; Korea Health Technology R&D Project; Novartis.

Citation Format: Eleftherios P Mamounas, Hanna Bandos, Barry C Lembersky, Jeon Hyeon Jeong, Charles E Geyer, Jr, Priya Rastogi, Louis Fehrenbacher, Mark L Graham, Stephen K Chia, Adam M Brufsky, Janice M Walshe, Gamini S Soori, Shaker R Dakhil, Thomas E Seay, James L Wade, III, Edward C McCarron, Soonmyung Paik, Sandra M Swain, D Lawerence Wickerham, Norman Wolmark. Ten-year results from NRG Oncology/NSABP B-42: A randomized, double-blinded, placebo-controlled clinical trial of extended adjuvant endocrine therapy with letrozole (L) in postmenopausal women with hormone-receptor+ breast cancer (BC) who have completed previous adjuvant therapy with an aromatase inhibitor (AI) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS4-01.