PF-00299804 (PF299) patient (pt)-reported outcomes (PROs) and efficacy in adenocarcinoma (adeno) and nonadeno non-small cell lung cancer (NSCLC): A phase (P) II trial in advanced NSCLC after failure of chemotherapy (CT) and erlotinib (E).

Abstract

7596 Background: Treatment (tx) options are limited for pts with NSCLC after failure of CT and E. Cough, dyspnea, and pain (chest) are key pt-reported NSCLC symptoms (symp). PF299 is an oral, irreversible, small-molecule pan-human epidermal growth factor receptor (-1, -2, and -4) tyrosine kinase inhibitor. Methods: This open-label, single-stage, P2 trial evaluated PF299 efficacy in pts with KRAS wild-type advanced NSCLC after failure of ≥1 CT regimen and E. Pts (adeno and nonadeno) received 45 mg PF299 once daily (3-week [wk] cycles [C]). Endpoints included response (primary), safety/tolerability, and PROs assessed by the EORTC-QLQ-C30/LC13 on day (D) 1 of each C (improvement of > 5 points [p] indicates meaningful benefit). Results: 65 pts (37 female, 50 adeno) have enrolled. Of 62 evaluable pts, 3 had a partial response and 35 stable disease (SD) ≥ 6 wks. 28 pts remained on treatment (tx) at C4D1 and had complete PRO data. Common tx-related adverse events (TRAEs) included diarrhea (86%), fatigue (40%), rash (45%), and stomatitis/mucosal inflammation (23%); mainly grade 1/2 and manageable. Pts reported an increase in “diarrhea” and “sore mouth” symp after C1 then gradual improvement. Qualitatively, raw scores for these symp moved from “not at all” at baseline to “a little” at C4D1. Importantly, pts reported clinically meaningful improvements (CMIs; > 5 p) in NSCLC symp. Mean baseline QLQ-LC13 scores were: dyspnea (21.4 p), cough (28.6 p), chest pain (14.3 p), and arm/shoulder pain (20.2 p). Improvements were: dyspnea (wk 6, 8.5 p; wk 9, 5.1 p), cough (wk 3, 8.8 p; wk 6, 5.9 p), chest pain (wk 3, 6.0 p; wk 6, 5.3 p; wk 9, 10.7 p), and arm/shoulder pain (wk 6, 10 p; wk 9, 8.3 p). Conclusions: Pts with adeno or nonadeno refractory NSCLC receiving PF299 in this study experience clinical benefit despite prior erlotinib tx. Pts report relief of NSCLC symp, including CMIs in key symp of cough, dyspnea, and pain. TRAEs were manageable. PRO results suggest that diarrhea and mucositis, while present, were tolerable. These results support further evaluation; a P3 trial of PF299 in refractory NSCLC is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gatekeeper Pharmaceuticals, Pfizer AVEO, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, MedImmune, Millennium, Novartis, OSI Pharmaceuticals, Pfizer, Roche, Schering-Plough, Syndax Pharmaceuticals Gatekeeper Pharmaceuticals, Pfizer Novartis, Pfizer Genzyme