Initial phase II results with crizotinib in advanced ALK-positive non-small cell lung cancer (NSCLC): PROFILE 1005.

Lung Cancer - Metastatic/Non-small Cell
Session Type and Session Title: 
Poster Discussion Session, Lung Cancer - Metastatic/Non-small Cell
Abstract Number: 



J Clin Oncol 29: 2011 (suppl; abstr 7514)


L. Crinò, D. Kim, G. J. Riely, P. A. Janne, F. H. Blackhall, D. R. Camidge, V. Hirsh, T. Mok, B. J. Solomon, K. Park, S. M. Gadgeel, R. Martins, J. Han, T. M. De Pas, A. Bottomley, A. Polli, J. Petersen, V. R. Tassell, A. T. Shaw; Azienda Ospedaliera di Perugia, Perugia, Italy; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Memorial Sloan-Kettering Cancer Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Department of Medical Oncology, The Christie National Health Services Foundation Trust, Manchester, United Kingdom; University of Colorado Denver, Aurora, CO; McGill University - Royal Victoria Hospital, Montreal, QC, Canada; Prince of Wales Hospital, Shatin, Hong Kong; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Karmanos Cancer Institute, Detroit, MI; University of Washington Seattle Cancer Care Alliance, Seattle, WA; Center for Lung Cancer, National Cancer Center, Goyang, South Korea; European Institute of Oncology, Milan, Italy; EORTC Headquarters, Brussels, Belgium; Pfizer Oncology, Milan, Italy; Pfizer Oncology, New York, NY; Pfizer Inc., La Jolla, CA; Massachusetts General Hospital Cancer Center, Boston, MA

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Abstract Disclosures


Background: The anaplastic lymphoma kinase (ALK) fusion gene is a key oncogenic driver in a subset of NSCLC patients (pts). Crizotinib is a potent, selective, ATP-competitive, small molecule ALK inhibitor. Pts with ALK-rearranged NSCLC had a high response rate to crizotinib in a prior expanded cohort study. Methods: This ongoing study included pts from 57 sites in 12 countries with ALK-rearranged NSCLC (by centralized FISH test) who progressed after ≥1 chemotherapy for recurrent/advanced/metastatic disease (including treated brain metastases). Pts received oral crizotinib 250 mg BID continuously in 3-week cycles. Disease response was evaluated by RECIST 1.1 every 6 weeks and safety/patient-reported outcomes (PRO; by EORTC QLQ-C30/QLQ-LC13 v3) were evaluated every 3 weeks. Results: Currently, 136 pts are evaluable for safety, 109 for PRO, and 76 for tumor response. Median age was 52 years, 94% had adenocarcinoma, 68% had never smoked, and 53% were female. Most pts (93%) had ≥2 prior chemotherapy regimens (range 1–11). Pts received a median 9 weeks of treatment (range 1–13 cycles started) and 88% remain on therapy. On a waterfall plot of tumor measurements in evaluable pts, 63 of 76 pts (83%) had target lesion shrinkage (41 pts had ≥30% shrinkage). Seven patients experienced objective progression by RECIST. The most frequent treatment-related AEs were nausea (46%), vision disorder (45%), vomiting (39%), and diarrhea (29%), mostly Grade 1/2. Treatment-related Grade 3/4 AEs were reported in 15% of pts (mostly increased ALT, dyspnea, and neutropenia). Two of the 9 deaths on-study were considered treatment-related (pneumonitis, unknown cause). Most pts had completed 4 PRO assessments by this review, with clinically significant (≥10 points) improvements in pain, cough, dyspnea and fatigue seen as early as cycle 2. Only a clinically significant increase in constipation was reported by patients over the course of therapy. Overall, quality of life was maintained. Conclusions: Data from a second global clinical study suggest crizotinib was safe and well-tolerated with preliminary evidence of improved symptoms and clinically meaningful antitumor activity in pts with pre-treated ALK-rearranged NSCLC.