Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study

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, Denis Moro-Sibilot, 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, Denis Moro-Sibilot

Abstract

Overall 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.

Keywords: ALK; alectinib; ceritinib; crizotinib; lung cancer.

Conflict of interest statement

CONFLICTS OF INTEREST

MD has received research funding from Novartis. He has been reimbursed for travel, accommodation, and/or other expenses by Novartis, Pfizer and Roche.

BB has received research funding from Novartis.

JC has received research funding from Novartis and Pfizer. He has served as a consultant (advisory board) for Novartis, Pfizer and Roche.

MP served as a consultant (advisory board) for Novartis, Pfizer, Roche and Lilly.

BM has served as a consultant (advisory board) for Novartis, Pfizer, Bristol-Myers Squibb, MSD and Lilly.

ED has received research funding from Roche. He has served as a consultant (advisory board) for Novartis, Pfizer, Roche and Lilly.

CAV has served as a consultant (advisory board) for Pfizer.

LM has been reimbursed for travel, accommodation, and/or other expenses by Pfizer.

RV has served as a consultant (advisory board) for Boehringer Ingelheim, Astra-Zeneca and Bristol-Myers Squibb.

ABC has served as a consultant (advisory board) for Novartis, Pfizer and Roche.

DMS has received research funding from Pfizer. He has served as a consultant (advisory board) for Novartis, Pfizer and Roche.

All remaining authors (LBG, RD, JH, JO, AMF, FG, PBR, AL, PM, FM) have declared no conflicts of interest.

Figures

Figure 1. Study flow chart
Figure 1. Study flow chart
Figure 2. Overall survival from the first…
Figure 2. Overall survival from the first crizotinib dose
Figure 3. Overall survival according to subsequent…
Figure 3. Overall survival according to subsequent systemic treatments initiated after progression on crizotinib in patients with documented progressive disease on crizotinib (n=263)
A. Overall survival from the first crizotinib dose and B. survival post-progressive disease on crizotinib for the 84 patients receiving next-generation ALK inhibitors after progression on crizotinib, compared with the 74 patients receiving subsequent treatments other than next-generation ALK inhibitors and the 105 patients receiving best supportive care only. C. Overall survival from the diagnosis of metastatic disease in the 84 patients receiving next-generation ALK inhibitors after progression on crizotinib.

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Source: PubMed

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