Phase III trial shows crizotinib superior to single-agent chemotherapy for ALK-positive lung cancer

VIENNA, Austria, 30 September 2012 -- The results of a new phase III trial show that crizotinib, a targeted therapy, is a more effective treatment than standard chemotherapy for patients with advanced, ALK-positive lung cancer, researchers said at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are found in about 5% of all lung cancers. In previous uncontrolled studies, crizotinib has been shown to induce significant clinical responses in patients with advanced ALK-positive lung cancer.

"This study is the first head-to-head comparison of crizotinib with standard chemotherapy in this patient group," said lead study author Dr Alice Shaw from Massachusetts General Hospital Cancer Center in Boston, USA. "In ALK-positive patients who have been previously treated with first-line, platinum-based chemotherapy, crizotinib is superior to standard single-agent chemotherapy in terms of response, progression-free survival and quality of life. These results establish crizotinib as the standard of care for patients with advanced, previously treated, ALK-positive lung cancer."

The current global randomized phase III study compared the efficacy and safety of crizotinib with standard chemotherapy with pemetrexed or docetaxel, in 347 patients with ALK-positive lung cancer who had already been treated with chemotherapy.

The study showed that crizotinib prolonged progression-free survival to a median of 7.7 months compared to 3.0 months among those patients who received the chemotherapy (HR 0.49; 95% CI 0.37𔂾.64 ;

So far, the analysis of the overall survival rate with the two drugs is still immature, Dr Shaw said. That is, not enough events have occurred to draw meaningful conclusions.

"It is important to note that there was significant crossover in this study," Dr Shaw said. "Patients who were randomized to receive chemotherapy and had disease progression were allowed to crossover to receive crizotinib. Hence, the majority of patients on the chemotherapy arm actually did receive crizotinib. This makes determination of overall survival benefit very challenging."

In this study, certain side-effects were more frequent with crizotinib compared with single-agent chemotherapy. "However, despite this, patients still reported improved quality of life on crizotinib compared with chemotherapy," Dr Shaw said.

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Commenting on the data, Dr Enriqueta Felip, Head of the Lung Cancer Unit in Oncology Department at Vall d'Hebron University Hospital in Barcelona, Spain and chair of the ESMO 2012 Metastatic NSCLC track (not involved in the study) said: "The results of this study are of great clinical relevance. Crizotinib, an oral drug, is more effective than standard chemotherapy in previously treated lung cancer patients with a specific molecular alteration, ALK. This is the first randomized study in a group of lung cancer patients selected precisely because they have ALK-positive tumors. After the worldwide implementation of targeted therapy in lung cancer patients defined by another molecular alteration --EGFR mutation, this is the second group of lung cancer patients to clearly benefit from a therapy directly targeting a molecular alteration. The results of this study represent a significant step towards individualized therapy in lung cancer patients."