488PRandomized trial of prophylactic minocycline for erlotinib-associated skin rash in non-small cell lung cancer (PEARL trial)

Abstract Background Acneiform rash as an adverse event often affects the treatment by EGFR-TKIs. Since minocycline has been suggested to reduce the rash, we assessed the efficacy and safety of prophylactic administration of minocycline simultaneously during erlotinib treatment. Methods Patients of ECOG performance status 0-2 with advanced NSCLC, who had not been treated with EGFR-TKIs and would receive erlotinib treatment were randomized 1:1 into either group A, with minocycline or group B, without minocycline. The patients assigned to group A were started on minocycline 100mg/day orally for 8 weeks with erlotinib. Primary end point was the frequency of grade ≥2 rash acneiform by independent assessment in first 8 weeks. We expected the prophylactic minocycline decreased the incidence of grade ≥2 skin rash from 50% to 30%. The planned sample size was 280 patients with a = 0.025 (one-sided) and b = 0.10. Results Patients accrual was started in March 2015 and ended in June 2018 because of slow accrual. Ninety-four patients were finally enrolled and 93 were full-analysis set. The median age of the patients was 71 years old (range 45 to 89),58 patients were female. EGFR mutation status positive/negative/unknown=78/13/2 patients. The frequency of grade ≥2 rash acneiformby independent assessment was 33.3% [95%C.I. 20.0-49.0%] in group A vs. 44.2% [95%C.I. 29.1-60.1%] in group B (p = 0.296). The frequency by physicians’ evaluation was 31.3% [95%C.I. 18.7-48.8%] and 45.5% [95%C.I. 30.4-61.2%] (p = 0.161). However, the frequency of grade ≥2 rash acneiform on day 15 by physicians’ evaluation was significantly decreased (4.4% [95%C.I. 5.3-14.8%] in group A vs. 25.0% [95%C.I. 13.2-40.3%] in group B (p = 0.005)). As for toxicity, the incidence of any grade skin-related toxicity as pruritus (39.6% vs. 63.6%) and pain of skin (14.6% vs. 25.0%) was less common in group A. Hence, anorexia (41.7% vs 20.5%), nausea (25.0% vs 4.5%), and dysgeusia (22.9% vs 15.9%) occurred more frequently. Conclusions Although the frequency of acneiform rash tended to decrease, prophylactic administration of minocycline is not recommended because of increasing gastrointestinal toxicity. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure T. Kozuki: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Chugai Pharmaceutical Co.; Honoraria (self), Research grant / Funding (self): Eli-Lilly Japan; Honoraria (self): Taiho Pharmaceutical Co.; Honoraria (self): Ono Pharmaceutical Co.; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): MSD; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Kyowa-Hakko Kirin; Honoraria (self): Pfizer; Honoraria (self): Nippon-kayaku; Research grant / Funding (self): Merck Biopharma. M. Takenoyama: Honoraria (self), Research grant / Funding (self): Chugai Pharmaceutical. All other authors have declared no conflicts of interest.