Studies: Zykadia shrank tumors in patients with ALK+ NSCLC

July 6, 2015

New data from two phase 2 studies showed ceritinib (Zykadia) shrank tumors in patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who had received previous treatment with an ALK inhibitor and in those receiving an ALK inhibitor for the first time.

New data from two phase 2 studies showed ceritinib (Zykadia) shrank tumors in patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who had received previous treatment with an ALK inhibitor and in those receiving an ALK inhibitor for the first time.

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The results of the Zykadia studies-ASCEND-2 and ASCEND-3 were presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

ASCEND-2 was a single-arm, open-label, multicenter phase 2 study of ceritinib in adult patients with ALK+ NSCLC previously treated with chemotherapy and crizotinib. At the August 13, 2014 data cut-off, 140 patients receiving oral ceritinib 750 mg daily had enrolled worldwide. In these patients, the overall response rate (ORR) was 38.6%, based on investigator assessment, following treatment with Zykadia. The most frequent adverse events with incidence of >50% were nausea (81.4%), diarrhea (80.0%) and vomiting (62.9%). The most frequent adverse events with incidence of >20% were nausea (81.4%), diarrhea (80.0%), vomiting (62.9%), increased alanine aminotransferase (43.6%), decreased appetite (40.7%), fatigue (36.4%), decreased weight (34.3%), increased aspartate aminotransferase (32.1%), abdominal pain (31.4%), constipation (28.6%), cough (21.4%), pyrexia (20.7%) and dyspnea (20.7%).

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ASCEND-3 evaluated adult patients with ALK+ NSCLC who had received up to 3 lines of chemotherapy and had no prior experience with an ALK inhibitor; in these patients, the ORR was 63.7%, based on investigator assessment, following treatment with Zykadia. The most frequent adverse events with incidence of >50% were diarrhea (82.3%), nausea (74.2%) and vomiting (66.9%). The most frequent adverse events with incidence of >20% were diarrhea (82.3%), nausea (74.2%), vomiting (66.9%), decreased appetite (49.2%), increased alanine aminotransferase (40.3%), abdominal pain (33.1%), fatigue (32.3%), increased aspartate aminotransferase (30.6%), decreased weight (29.0%), increased gamma-glutamyl transferase (GGT) (26.6%), increased blood creatinine (21.0%) and increased blood alkaline phosphatase (20.2%). 

Comparable ORR results were observed in patients with ALK+ NSCLC who entered the studies with brain metastases: 33.0% in ASCEND-2 and 58.0% in ASCEND-3.

 

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“The ASCEND-2 data support Zykadia’s efficacy in patients with ALK+ NSCLC who were previously treated with an ALK inhibitor, while the ASCEND-3 data add to our growing understanding of Zykadia’s efficacy in treating patients with ALK+ NSCLC who are receiving an ALK inhibitor for the first time,” said Enriqueta Felip, MD, PhD, Head of the Lung Cancer Unit, Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain.

Additionally, in ASCEND-2 and ASCEND-3, brain metastases at baseline were seen in 71.4% and 40.3% of patients, respectively. The ORR, median duration of response (DOR) and median progression-free survival (PFS) for patients with brain metastases at baseline were similar with those reported for the overall patient populations in these studies.

Dr Felip offered the following take-away points:

  • Disease progression is often inevitable for patients following treatment with an ALK inhibitor, highlighting the need for more treatment options.

  • The ASCEND-2 data support Zykadia’s efficacy in patients with ALK+ NSCLC who were previously treated with an ALK inhibitor.

  • The ASCEND-3 data add to our growing understanding of Zykadia’s efficacy in treating patients with ALK+ NSCLC who are receiving an ALK inhibitor for the first time.

  • In ASCEND-2 and ASCEND-3, the ORR, DOR and PFS for patients with brain metastases at baseline were similar with those reported for the overall patient populations in these studies. “These data are important as up to 50% of patients with ALK+ NSCLC can develop brain metastases, making them one of the biggest challenges in treating ALK+ NSCLC,” she said.

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