{"entity":{"id":"paper-ascend-4-lancet-2017","kind":"paper","name":"First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study","aka":[],"tldr":"The primary report of ASCEND-4: untreated ALK-positive lung cancer stayed under control for a median of 16.6 months on ceritinib against 8.1 months on platinum chemotherapy.","summary":"Randomised, open-label phase 3 study at 134 centres in 28 countries in untreated stage IIIB or IV ALK-rearranged non-squamous non-small-cell lung cancer. Patients were assigned to oral ceritinib 750 mg a day or platinum-based chemotherapy (cisplatin or carboplatin plus pemetrexed every 3 weeks for four cycles followed by pemetrexed maintenance), stratified by performance status, previous neoadjuvant or adjuvant chemotherapy and brain metastases. The primary endpoint was progression-free survival by blinded independent review committee in the full analysis set.\n\nBetween August 2013 and May 2015, 376 patients were randomised (189 ceritinib, 187 chemotherapy). Median progression-free survival was 16.6 months (95% CI 12.6 to 27.2) with ceritinib and 8.1 months (95% CI 5.8 to 11.1) with chemotherapy (hazard ratio 0.55, 95% CI 0.42 to 0.73). The most common adverse events on ceritinib were diarrhoea (85 percent), nausea (69 percent), vomiting (66 percent) and raised alanine aminotransferase (60 percent). Funded by Novartis.","asOf":"2026-09-24","links":[{"label":"The Lancet 2017","url":"https://doi.org/10.1016/S0140-6736(17)30123-X"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28126333/"},{"label":"ClinicalTrials.gov NCT01828099","url":"https://clinicaltrials.gov/study/NCT01828099"}],"tags":[],"related":[],"cancers":["nsclc","alk-positive-nsclc"],"sections":[],"technologies":[],"targets":["alk"],"drugs":["ceritinib"],"companies":["novartis"],"institutions":[],"pathways":[],"terms":[],"trials":["nct01828099"],"people":["jean-charles-soria","luis-paz-ares","juergen-wolf","chong-jen-yu"],"bottlenecks":[],"keyPapers":[],"journals":["lancet"],"dependsOn":[],"notes":[],"journal":"The Lancet","year":2017,"doi":"10.1016/S0140-6736(17)30123-X","pmid":"28126333","authors":"Soria JC, Tan DSW, Chiari R, et al.","paperType":"rct","findings":["Median progression-free survival 16.6 vs 8.1 months by blinded independent review; hazard ratio 0.55 (95% CI 0.42 to 0.73).","376 patients randomised at 134 centres in 28 countries between August 2013 and May 2015.","Diarrhoea 85%, nausea 69%, vomiting 66% and raised alanine aminotransferase 60% on ceritinib."],"whatItMeans":"ASCEND-4 gave ceritinib its 2017 US first-line approval and showed that a second-generation ALK inhibitor beats chemotherapy in untreated disease. In practice alectinib, brigatinib and lorlatinib, tested against crizotinib rather than chemotherapy, became the usual first-line choices, partly because ceritinib's gut side effects at 750 mg fasted were hard to live with.","caveats":["Open-label; the comparator was chemotherapy, not crizotinib, which was already standard when the trial ran.","Overall survival was not reported in the abstract and was not significantly different at the prespecified interim analysis in the US label.","The 750 mg fasted dose studied here was later replaced in the label by 450 mg with food."],"changedPractice":true,"participants":376},"route":"/key-papers/paper-ascend-4-lancet-2017/","neighbours":{"cancer":[{"id":"alk-positive-nsclc","kind":"cancer","name":"ALK-positive non-small-cell lung cancer","route":"/cancers/alk-positive-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"}],"drug":[{"id":"ceritinib","kind":"drug","name":"Ceritinib","route":"/drugs/ceritinib/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"trial":[{"id":"nct01828099","kind":"trial","name":"ASCEND-4","route":"/trials/nct01828099/"}],"person":[{"id":"chong-jen-yu","kind":"person","name":"Chong-Jen Yu","route":"/people/chong-jen-yu/"},{"id":"jean-charles-soria","kind":"person","name":"Jean-Charles Soria","route":"/people/jean-charles-soria/"},{"id":"juergen-wolf","kind":"person","name":"Jürgen Wolf","route":"/people/juergen-wolf/"},{"id":"luis-paz-ares","kind":"person","name":"Luis Paz-Ares","route":"/people/luis-paz-ares/"}],"journal":[{"id":"lancet","kind":"journal","name":"The Lancet","route":"/journals/lancet/"}]}}