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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.
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.
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.
Shares Ceritinib, ALK-positive non-small-cell lung cancer, Novartis, Non-small-cell lung cancer.
Shares Jürgen Wolf, Novartis, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares ASCEND-4, ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares ASCEND-4, ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.
Shares ALK-positive non-small-cell lung cancer, ALK, Non-small-cell lung cancer.