“The results of ALTER 1202 are incredible, not just for the survival benefit they reveal for anlotinib third-line in small-cell lung cancer (SCLC), but also for the magnitude of this benefit,” says Professor Sanjay Popat from The Royal Marsden NHS Foundation Trust, London, UK, commenting on the updated survival results being presented today (‘Proffered Paper 1 – Non-metastatic NSCLC and other thoracic malignancies [SCLC]’, 16.30–18.00, Cordoba Auditorium, Hall 7).
Anlotinib provided a 2.4-month overall survival advantage compared with placebo (7.3 months versus 4.9 months) in the final analysis of ALTER 1202, a randomised, phase II, double-blind, Chinese trial in 120 patients with SCLC failing at least 2 lines of chemotherapy (Abstract 1738O). The survival benefit was particularly pronounced in patients with brain metastases (6.3 months versus 2.6 months; hazard ratio [HR] 0.23; p=0.0009) and those receiving anlotinib third line (7.3 months versus 4.9 months; HR 0.50; p=0.0051).
“These data are potentially practice changing in China, where anlotinib is being developed,” says Popat. “It is very exciting to see the activity in patients with brain metastases, which is consistent with the inhibition of vascular endothelial growth factor-induced signalling demonstrated by this multitargeted angiokinase inhibitor.”
In terms of next steps, “Combination trials are already being planned with anlotinib,” says Popat, “and it makes absolute sense to move studies into the second-line and even first-line settings. But we need to think carefully about how anlotinib can be incorporated into current treatment approaches. With IMpower133 and the ongoing CASPIAN trial, checkpoint inhibitors are a part of first-line therapy and we need to make sure that benefit does not come at the price of toxicity.” Identification of biomarkers would help to tailor the use of anlotinib. “But this is really tough,” warns Popat, “mainly because of the number of different targets involved, and we have yet to identify a good biomarker.” Concluding, he says, “It would be really interesting to see some studies involving Caucasian patients treated in a Western healthcare setting to enable us to assess the value of anlotinib in different populations.”
ESMO Congress 2019 abstract:
1738O – Overall survival (OS) update in ALTER 1202: Anlotinib as third-line or further-line treatment in relapsed small-cell lung cancer (SCLC)