113MO NATALEE update: Safety and treatment (tx) duration of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC)

In NATALEE, RIB + NSAI showed a significant invasive disease-free survival (iDFS) benefit (HR, 0.749; 95% CI, 0.628-0.892; 1-sided P=.0006) vs NSAI alone in men and pre-/postmenopausal women with HR+/HER2− EBC. Understanding RIB tolerability is key for clinical decision making. We report RIB safety and tx duration in NATALEE. Pts in NATALEE were randomized 1:1 to RIB (400 mg/d 3 wk on/1 wk off, 36 mo) + NSAI (letrozole or anastrozole, ≥60 mo) or NSAI alone. Men and premenopausal women also received goserelin. In this analysis, pts were followed for safety/tolerability for ≤36 mo + 30 d follow-up. At the final iDFS analysis, 1997/2525 (79.1%) pts in the safety set had discontinued RIB. Most pts (1752 69.4%) had completed ≥24 mo of RIB, while 1091 (43.2%) had completed 36 mo of RIB; 528 (20.9%) pts were still on RIB. The median relative dose intensity (RDI) during RIB tx was 94%.Adverse events (AEs) occurred in 2474 (98.0%) pts in the RIB arm (NSAI alone: 2145/2442 87.8%; Table); of these, 2368 (93.8%) were likely related to a treatment component (NSAI alone: 1566 64.1%). Serious AEs occurred in 357 (14.1%) pts on RIB (NSAI alone: 256 10.5%). AEs led to RIB dose interruptions in 1671 (66.2%) pts and RIB dose reductions in 576 (22.8%) pts. Early RIB discontinuations due to AEs were reported in 498 (19.7%) pts. Median time to AE-related discontinuation was 4 mo. Grade ≥2 neutropenia (Kaplan–Meier KM median, 1.0 mo) and AST/ALT elevations (KM median, not reached) generally first occurred within 3 mo. QTcF increase from baseline >60 ms occurred in 19 (0.8%) pts (NSAI alone: 2 0.1%).Table: 113MOMost common AEs (>10% in RIB + NSAI arm in the safety set)AEs, n (%)RIB + NSAI n = 2525NSAI alone n = 2442Neutropeniaa1579 (62.5)113 (4.6)Infectionsa1253 (49.6)883 (36.2)Arthralgia942 (37.3)1058 (43.3)Hepatobiliary toxicitya,b667 (26.4)273 (11.2)Leukopeniaa595 (23.6)111 (4.5)Nausea588 (23.3)190 (7.8)Headache575 (22.8)415 (17.0)Fatigue564 (22.3)322 (13.2)Hot flush486 (19.2)489 (20.0)Asthenia428 (17.0)291 (11.9)Alopecia380 (15.0)109 (4.5)Diarrhea366 (14.5)135 (5.5)Constipation335 (13.3)123 (5.0)Cough332 (13.1)201 (8.2)Insomnia292 (11.6)281 (11.5)Pyrexia280 (11.1)147 (6.0)Back pain272 (10.8)247 (10.1)Pain in extremity261 (10.3)219 (9.0)aGrouped term per MedDRA v. 26.0bAST, ALT, ALP, bilirubin, and GGTP elevations Open table in a new tab aGrouped term per MedDRA v. 26.0 bAST, ALT, ALP, bilirubin, and GGTP elevations With the majority of pts completing RIB tx, these data confirm that RIB-related AEs and dose-related adjustments occurred early, highlighting the importance of timely management of AEs. RIB was well-tolerated in NATALEE with current dose adjustment guidelines.