Crossover from one aromatase inhibitor (AI) to another in the Exemestane and Letrozole Pharmacogenetics (ELPh) trial.

Abstract

158 Background: Tolerance of AI therapy can be poor due to treatment-emergent toxicities and can lead to early discontinuation (non-persistence). Patients often switch from one AI to another when toxicities develop; however, limited prospective data exist on patients who switch AI. Here we describe the effect of switching from E to L or L to E on tolerance of and persistence with therapy. Methods: Postmenopausal women initiating AI therapy were enrolled on the ELPh trial and randomized to E or L. Those that stopped their AI for self-reported intolerance were offered crossover to alternate AI after a 2-6 week washout. Kaplan-Meier estimates of proportions on AI after 1, 3, and 6 months were assessed during 1st and 2nd AI. Associations between time on 2ndAI and clinicopathologic factors were analyzed using univariable Cox proportional hazards model. To evaluate effect of crossover on patient-reported outcomes, multiple questionnaires, including a pain visual analog scale (VAS), were assessed serially. Results: 83 women, mean age 60 years, 45% prior chemotherapy, and 31% with prior tamoxifen use, participated in the crossover protocol. 71% reported improvement in symptoms a mean 4.72 weeks after discontinuing 1st AI therapy. Median time on 1st AI was 6.8 months (95% CI 5.8-9 months), and on 2nd AI was 11.5 months (6.9-24.2). The probability of persistence at 1, 3, and 6 months for the 1st AI was 94%, 76%, and 55% and for the 2nd AI was 89%, 73%, and 62%, respectively. There was no significant association between duration on 2nd AI and 1st AI (L vs. E), duration on 1st AI, age, body mass index, or prior therapies. The change in pain VAS from baseline to 1 or 3 months was not significantly different during treatment with the 1st or 2ndAI. Conclusions: Although all AI medications have similar mechanisms of activity, nearly two-thirds of patients who are intolerant of one AI are able to maintain therapy for at least 6 months following switch to 2nd AI. Switching is a reasonable approach for women who cannot tolerate 1st AI that may improve persistence with therapy. The mechanisms for intrapatient variation in tolerance warrant further study. Clinical trial information: NCT00228956.