# 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

Source: https://onco.cc/key-papers/paper-ascend-4-lancet-2017/  
OnCo record `paper-ascend-4-lancet-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Between 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: The Lancet
- Year: 2017
- DOI: 10.1016/S0140-6736(17)30123-X
- Authors: Soria JC, Tan DSW, Chiari R, et al.
- 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.
- What it means: 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.

## Sources

- The Lancet 2017: https://doi.org/10.1016/S0140-6736(17)30123-X
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28126333/
- ClinicalTrials.gov NCT01828099: https://clinicaltrials.gov/study/NCT01828099

## Connected records

- cancers: [ALK-positive non-small-cell lung cancer](https://onco.cc/cancers/alk-positive-nsclc/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- targets: [ALK](https://onco.cc/targets/alk/)
- drugs: [Ceritinib](https://onco.cc/drugs/ceritinib/)
- companies: [Novartis](https://onco.cc/companies/novartis/)
- trials: [ASCEND-4](https://onco.cc/trials/nct01828099/)
- people: [Chong-Jen Yu](https://onco.cc/people/chong-jen-yu/), [Jean-Charles Soria](https://onco.cc/people/jean-charles-soria/), [Jürgen Wolf](https://onco.cc/people/juergen-wolf/), [Luis Paz-Ares](https://onco.cc/people/luis-paz-ares/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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