Survival outcomes according to ramucirumab (RAM)-related hypertension (HTN) in patients (pts) with advanced HER2-negative gastric (G) or gastro-esophageal junction (GEJ) cancer: An exploratory analysis of the phase III ARMANI trial.

Abstract

4051 Background: Retrospective studies suggest an association between treatment-related HTN and improved outcomes with anti-angiogenic agents, with most evidence derived from colorectal cancer pts treated with bevacizumab. Data on the prognostic significance of RAM-induced HTN are limited. We therefore explored the association between treatment-related HTN and survival outcomes in the ARMANI trial. Methods: ARMANI was a phase III trial enrolling pts with advanced HER2-negative G/GEJ cancer who had disease control after a 3-month first-line fluoropyrimidine and oxaliplatin (FOX) induction chemotherapy. Pts were randomized to switch maintenance with paclitaxel plus RAM (PTX-RAM) or the continuation of FOX. The objectives of this exploratory analysis were to evaluate the association between grade (G)≥2 HTN and survival outcomes across treatment arms (using the FOX arm as reference [ref]) and within the PTX–RAM arm. To mitigate time-related bias, Cox proportional hazards models were fitted with HTN modeled as a time-dependent covariate, considering pts ‘non-HTN’ until G≥2 HTN onset and ‘HTN’ thereafter. Because HTN is a post-randomization event, survival analyses in the PTX-RAM arm by HTN status were adjusted for baseline characteristics using inverse probability weighting based on propensity scores derived from a logistic regression model. Results: Among 276 pts (141 in PTX-RAM and 135 in FOX arm), G≥2 HTN occurred in 20 cases (7.2%), all observed in the PTX-RAM arm (20/141, 14.2%). The incidence of G≥2 HTN was similar between males and females (15.8% versus 10.9%) and between pts aged < 70 and ≥70 years (14.4% versus 13.5%). Median time to G≥2 HTN-onset was 3 months. In the between-arm comparison, the PTX–RAM arm showed improved progression-free survival (PFS) versus FOX regardless of HTN development (p = 0.192). In contrast, the overall survival (OS) benefit was greater in the HTN group (p = 0.071). These findings are detailed in the Table below. In analyses restricted to the PTX–RAM arm, G≥2 HTN onset was associated with improved OS (HR 0.43; 95% CI, 0.22-0.83; p = 0.033), whereas no significant difference was observed for PFS (HR 0.88; 95% CI, 0.50-1.57; p = 0.735). Conclusions: The development of G≥2 HTN was associated with a significant OS benefit in pts treated with PTX–RAM in the ARMANI trial. These findings support further research to identify biomarkers predictive of HTN onset to refine pts selection for switch maintenance strategies. Clinical trial information: NCT02934464 . Median PFS (months) (95% CI) HR (95% CI) Median OS (months) (95% CI) HR (95% CI) FOX 3.5 (2.8−4.2) ref 10.5 (8.5−13.5) ref PTX-RAM (non-HTN) 6.5 (5.8−7.7) 0.44 (0.32−0.60) 12.2 (10.6−14.4) 0.65 (0.49−0.87) PTX-RAM (HTN) 9.0 (4.2−16.9) 0.61 (0.38−0.99) 24.6 (13.3−64.4) 0.39 (0.22−0.69)