((B-011)) (B-011) Association Between Non-adherence to Oral Anticancer Monotherapy in Clinical Trials (CTs) and Progression-Free Survival (PFS) in Patients (pts) with R/R Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

Background: In CTs, medication non-adherence can underestimate treatment (tx) efficacy and incur additional operational costs. While regulatory bodies emphasize adherence assessment, little is reported on adherence to oral anticancer therapies in CTs.

Objectives: This study examined the association between non-adherence to oral anticancer monotherapy in CTs and PFS in pts with R/R CLL/SLL.

Methods: Adult pts with R/R CLL/SLL receiving oral monotherapy (BTKi, BCL2i, or PI3Ki) from < 5 CTs conducted worldwide between 2013 and 2022 were sourced from the Medidata Clinical Cloud®. The index date was defined as 360 days post-tx initiation. Pts alive, without progression (PD), and not censored by the index date were included. Non-adherence was defined as any deviation from the intent-to-treat protocol and measured using the proportion of days covered (PDC). PDC was calculated for 12 consecutive 30-day intervals following tx initiation, with pts considered non-adherent in each interval if their PDC was < 80%. Adherence trajectory (AdhT) groups were identified using group-based trajectory modeling. PFS was defined as the time from the index date to PD or death. 1:1 exact matching was performed to balance the key baseline characteristics of AdhT groups. The association between AdhT groups and PFS was assessed in the matched sample using unadjusted and adjusted Cox models.

Results: Of 1273 pts included in CTs, 999 were eligible for analysis at the index date. Two distinct AdhT groups were observed: consistently high adherence (913 pts; mean PDC 0.97) and declining adherence (86 pts; mean PDC 0.37). 84 (98%) of the 86 pts with declining adherence were matched with pts with high adherence, resulting in a matched sample of 168 pts (63% aged ≥ 65 years [y]; 62% male; 94% White; ECOG 0-1/2: 98%/2%; prior lines of therapy 1/2/3/4+: 54%/25%/11%/11%; BCL2i/non-BCL2i: 42%/58%; highest grade of tx-related adverse event [AE] 3-4/1-2/no AE: 73%/25%/2%; and median follow-up: 2.7 y [IQR: 2.1-3.2]). Median PFS from the index date was 40.4 months (95% CI: 29.3, not reached [NR]) for pts with declining adherence and NR for pts with high adherence. Pts with declining adherence had significantly shorter PFS compared to those with high adherence (unadjusted hazard ratio [HR]: 2.08 [95% CI: 1.23, 3.54; P = 0.007]; adjusted HR: 2.20 [95% CI: 1.28, 3.80; P = 0.004]).

Conclusions: This analysis showed a significant relationship between adherence and efficacy outcome in CTs in pts with R/R CLL/SLL, highlighting the importance of adherence to tx. However, the strict adherence definition may overestimate non-adherence. Future research should evaluate the reasons for non-adherence and consider strategies to reduce non-adherence in CTs.