Rapid and Dramatic Radiographic and Clinical Response to an ALK Inhibitor (Crizotinib, PF02341066) in an ALK Translocation-Positive Patient with Non-small Cell Lung Cancer

A 32-year-old Chinese female never smoker presented with persistent cough in June 2009, and imaging studies revealed a right hilar mass. An endobronchial biopsy of the tumor revealed a moderately differentiated mucinous adenocarcinoma that was cytokeratin 7 (CK7) positive, CK20 negative, transcription tissue factor-1 (TTF-1) positive, and mucicarmine positive. Initial molecular analysis revealed the tumor to be both epidermal growth factor receptor and KRAS wild type. Her staging workup revealed metastasis to the liver and brain. She underwent stereotactic radiosurgery of her brain metastases that was followed by six cycles of cisplatin/pemetrexed/bevacizumab combination chemotherapy followed by bevacizumab maintenance therapy, with a partial response to treatment. In November 2009, she decided to undertake a treatment holiday for 3 months. By February 2010, however, her disease had progressed, and she commenced single-agent erlotinib treatment but had documented disease progression after 6 weeks. She was referred by her treating oncologist for possible enrollment into the phase I crizotinib trial because her clinical profile—young age, adenocarcinoma histology, never-smoking status, and most importantly her tumor is wild type for epidermal growth factor receptor and KRAS—fits the profile of an anaplastic lymphoma kinase (ALK)-positive patient with non-small cell lung cancer (NSCLC).