Pazopanib with low fat meal (PALM) in advanced renal cell carcinoma (RCC)

• Published in: Journal of clinical oncology Vol. 36; no. 6_suppl; p. 683
• Main Authors: Reimers, Melissa Andrea, Daignault, Stephanie, Shango, Maryann, Dedinsky, Rachel, Riddle, Liam, Wen, Bo, Redman, Bruce G., Alva, Ajjai Shivaram
• Format: Journal Article
• Language: English
• Published: 20.02.2018
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2018.36.6_suppl.683

Abstract only 683 Background: Pazopanib, a highly lipophilic standard first-line therapy for metastatic RCC, is conventionally taken in a fasting state but has significant gastrointestinal toxicities and 96% of ingested drug is fecally excreted, with major financial implications. Single dose studies with fat meals suggested bioavailability is increased two-fold. We sought to evaluate toxicity/safety, bioavailability and anti-tumor efficacy of daily pazopanib taken with a low fat meal over 12 weeks. Methods: Enrolled pts had unresectable locally advanced or metastatic RCC with clear cell component, RECIST 1.1 measurable disease, ECOG PS ≤2, adequate organ function, and up to 3 prior therapies including VEGF(R) and checkpoint inhibitors. Subjects took pazopanib, starting dose of 400 mg, once daily with low-fat meal ( < 400 cal with < 20% fat/10 g of fat) in 2 wk cycles with MD discretion to dose-escalate q2wks up to 800 mg or irreversibly dose-reduce as low as 200 mg based on tolerance/toxicity for 12 wks. Baseline and end of study echocardiograms, and triplicate ECGs at each cycle start were monitored. Home pill diaries were collected. PK was analyzed in the first 3 cycles. Results: Sixteen pts were accrued: median age 60 (range: 47 – 75),75% men,11 were ECOG PS 0. Most (12/16) subjects with no prior therapy, 13/16 had intermittent Heng risk criteria, 3 favorable; 5 sarcomatoid component. Diet compliance by pill diary was outstanding, except for 1 pt for 1 cycle. Calculated mean daily dose was 535 mg (153-750 mg). Therapy was well tolerated; 5 Grade 3 AEs (1 HTN, 1 chest pain, 2 AST/ALT elevations, 1 Abd pain) occurred. LVEF declined by > 15% in 3 pts but none to < 50%. QTc prolongation > 450 ms did not occur. All but 3 pts completed protocol (off d/t toxicity-HTN, LFTs, chest pain). ORR was PR 5 (31%); SD 7 (44%). PK data and pharmacogenomics CYP3A4 polymorphism data correlated with toxicity. Conclusions: Pazopanib taken with a low fat meal appears to be better tolerated compared to published data on empty stomach administration, especially with fewer GI toxicities, including diarrhea. It also resulted in comparable efficacy with fewer cumulative pills over the 12-week period, with substantial cost implications. Larger trials of pazopanib with low fat meal are warranted. Clinical trial information: NCT02729194.