Roche's ALK inhibitor Alecensa (alectinib) has demonstrated long-term survival benefits exceeding 7 years in patients with ALK-positive advanced non-small cell lung cancer (NSCLC).

In the final overall survival (OS) analysis of the Phase III ALEX study, Alecensa showed a clear survival benefit over existing treatments, reaffirming its status as the standard first-line therapy.


Median survival 81 months...“Changes the patient survival curve in the first-line treatment landscape”

According to the updated ALEX results (LBA73) presented on October 17 (local time), the median OS with Alecensa was 81.1 months (95% CI 62.3–NE) compared to 54.2 months (95% CI 34.6–75.6) with crizotinib, representing an improvement of approximately 27 months.

Professor Tony S.K. Mok of the Chinese University of Hong Kong, who presented the findings, stated, “Alecensa reduced the risk of death by about 22% (HR 0.78, 95% CI 0.56–1.08). Although OS was a secondary endpoint, the improvement is clinically meaningful and clearly directional.”

Importantly, the final analysis confirmed sustained survival benefits even among patients with brain metastases.

Professor Mok stated, “Among patients with brain metastases who received radiotherapy, median OS reached 92 months with alectinib versus 39 months with crizotinib, which is more than double.”

Additionally, in patients with brain metastases who had not undergone radiation therapy, alectinib showed a survival period of 47 months, demonstrating a clear advantage over crizotinib (approximately 24 months).

Furthermore, in the patient group without brain metastases, the median survival period reached 94 months with alectinib treatment, drawing a long-term survival curve exceeding 7 years.

Professor Mok emphasized, “Alectinib's efficacy was maintained regardless of brain metastasis status or prior radiotherapy. The strong CNS penetration of alectinib likely contributed to this durable control and fundamentally changed the survival trajectory for these patients.”

Response duration 4 times longer… Long-term treatment tolerability also ‘good’

The duration of response (DoR) in the alectinib group was 42.3 months (95% CI 31.3–51.3), approximately 4 times longer than the 11.1 months (95% CI 7.9–13.0) observed in the crizotinib group.

Prof. Mok said, “This once again demonstrates alectinib's strength in providing a long and stable treatment response. Safety analysis also showed it maintained a stable safety profile during long-term administration.”

The 7-year OS rate was 48.6% with Alecensa and 38.2% with crizotinib. Compared to the historical chemotherapy era (median survival ~8 months), this represents a tenfold improvement.

“The fact that half of the patients with advanced lung cancer survived for more than 5 years demonstrates a complete paradigm shift in first-line treatment.”

However, Professor Christine M. Lovly of Vanderbilt University in the US, who led the invited discussion that followed the presentation, also mentioned some limitations of the study.

Professor Lovly pointed out, “25% of the crizotinib group subsequently used alectinib, and this crossover made it difficult to achieve statistical significance (p=0.132).”

Nevertheless, Professor Lovly stated, “The trend toward survival extension is clear, and the consistent benefit observed in patients with brain metastases is undeniable. The ALEX study is a landmark study that ushered in the era of ALK inhibitors. Now, we must evolve toward precision therapy that reflects molecular characteristics such as TP53 mutations and baseline ctDNA status.”

Concluding the presentation, Professor Mok said, “The ALEX study sets a new benchmark—showing that 7-year survival is now an attainable goal for ALK-positive lung cancer patients. Alecensa will continue to extend survival safely and stably as the first-line standard of care.”