Ceritinib Shows Longer Progression-Free Survival in Lung Cancer Treatment

Non-small cell lung cancer (NSCLC) patients pre-treated with crizotinib were found to have longer progression-free survival when treated with ceritinib compared to chemotherapy, a new study found.

The phase 3 ASCEND-5 study enrolled 231 patients with NSCLC who received crizotinib. The findings were presented at the ESMO 2016 Congress in Copenhagen.

“Patients with non-small cell lung cancer should receive front line therapy with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib,” said lead study author Giorgio Scagliotti. “Most patients develop resistance to crizotinib and currently second line treatment is represented by chemotherapy alone. This was the first phase 3 study to assess whether the second generation ALK inhibitor ceritinib was superior to chemotherapy upon progression on crizotinib therapy in NSCLC.”

Study participants were randomized 1:1 to receive therapy with ceritinib or chemotherapy (pemetrexed or docetaxel). Any patient who discontinued chemotherapy because of disease progression was able to switch to ceritinib.

The study was assessed by a blinded independent review committee, and the primary endpoint was progression-free survival.

The results of the study showed that median progression-free survival significantly improved with ceritinib compared with chemotherapy (5.4 versus 1.6 months, hazard ration [HR] 0.49, p<0.001). Ceritinib was found to increase the overall response rate by 39.1%, compared to 6.9% with chemotherapy. No improvement was seen in overall survival with ceritinib compared with chemotherapy.

“Progression-free survival was significantly lengthened with ceritinib compared to chemotherapy,” Scagliotti said. “We did not observe an improvement in overall survival with ceritinib, probably because the patients who crossed over diluted the potential benefit.”

Of the patients who discontinued chemotherapy because of disease progression, 75 crossed over to ceritinib.

“This study opens up a new treatment paradigm after crizotinib failure,” Scagliotti said. “It would be logical now to give a sequence of active drugs, starting with crizotinib in first line and moving to ceritinib in second line.”

Any toxicities observed in patients taking ceritinib were similar to those seen in phase 1 and 2 studies. The most common grade 3/4 adverse events with ceritinib were nausea, vomiting, and diarrhea. Chemotherapy-induced adverse events included neutropenia, fatigue, and nausea.

Compared with placebo, ceritinib was found to significantly improve patient-reported outcomes, including lung cancer-specific symptoms and overall health status.

“This is the first randomized study to examine how a second generation ALK inhibitor compares to standard second line chemotherapy in ALK positive patients who failed the standard first line therapy, which currently is crizotinib,” said researcher Alice Shaw, director of thoracic oncology at Massachusetts General Hospital Cancer Center. “Single arm studies have suggested that ceritinib and alectinib could be standard options in the second line setting after crizotinib has failed. But the positive effect on progression-free survival in this phase 3 study confirms that there is greater benefit using a second ALK inhibitor over standard chemotherapy. This will establish sequential crizotinib followed by a second generation ALK inhibitor as the standard treatment for patients with metastatic ALK positive lung cancer.”