• Michaël Duruisseaux, Benjamin Besse, Jacques Cadranel, Maurice Pérol, Bertrand Mennecier, Laurence Bigay-Game, Renaud Descourt, Eric Dansin, Clarisse Audigier-Valette, Lionel Moreau, José Hureaux, Remi Veillon, Josiane Otto, Anne Madroszyk-Flandin, Alexis Cortot, François Guichard, Pascaline Boudou-Rouquette, Alexandra Langlais, Pascale Missy, Franck Morin, and Denis Moro-Sibilot.
• Centre Hospitalier Universitaire Grenoble Alpes, Thoracic Oncology Unit, Chest Department, Grenoble, France.
• Oncotarget. 2017 Mar 28; 8 (13): 21903-21917.

AbstractOverall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

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