ASCEND-4: Ceritinib Improved PFS in ALK-Positive NSCLC

Patients treated with first-line ceritinib had a 45% reduction in the risk for progression of advanced ALK-positive NSCLC compared with chemotherapy.

Patients treated with first-line ceritinib had a 45% reduction in the risk for progression of advanced anaplastic lymphoma kinase (ALK)-positive non–small-cell lung cancer (NSCLC) compared with chemotherapy, according to the results of the ASCEND-4 trial (abstract PL03.07) presented at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer, held December 4–7 in Vienna.

“Ceritinib should now be considered as a new option in those patients diagnosed with ALK-rearranged NSCLC,” said Gilberto De Castro, Jr, MD, of the Instituto do Cancer do Estado de Sao Paulo, Brazil, during a press conference.

According to De Castro, in the Western world ALK-positive tumors occur in about 4% to 5% of all patients, but if you just look at non-smokers they can occur in as many as 15% of patients. Up to now, first-line treatment for these patients was chemotherapy or crizotinib, a first-generation ALK inhibitor.

Ceritinib is a second-generation ALK inhibitor. This trial included 376 patients with previously untreated ALK-positive, advanced, nonsquamous NSCLC. Patients were randomly assigned to ceritinib 750 mg per day (n = 189) or chemotherapy with pemetrexed plus cisplatin or carboplatin (n = 187) followed by maintenance pemetrexed.

Patients assigned ceritinib had significantly improved progression-free survival (PFS) compared with chemotherapy (hazard ratio, 0.55; P < .001). The median PFS was 16.6 months for ceritinib compared with 8.1 months for chemotherapy. Additionally, the objective response rate for ceritinib was also significantly higher (72.5% vs 26.7%).

“This improvement in PFS was robust and, very importantly, consistent across many subgroups of patients including those with and without brain metastases,” De Castro said. In patients without brain metastases, the PFS was 26 months. In patients with brain metastases, it was 10.7 months.

Additionally, patients assigned ceritinib had a longer duration of response compared with chemotherapy (24 vs 11 months).

According to De Castro, adverse events on ceritinib are frequent, but in general they are considered manageable and acceptable. For example, only 5% of patients on ceritinib had to discontinue treatment due to adverse events, he said.

“It is more important than ever to consider nonsquamous NSCLC as a very heterogeneous disease,” De Castro noted. “For every patient we treat we need to submit a sample to the lab and ask the pathologist to check for genetic alterations that can drive the carcinogens in this patient.”