Additional Perspectives

The investigators noted that when the trial was initiated, there were few third-line options available for patients with NSCLC. However, they pointed out that “a dramatic change has taken place in the past 2 years. The development of immune checkpoint inhibitors has placed docetaxel or checkpoint inhibition as a third-line therapy.” 

Dr West agreed, stating that immunotherapy is now the standard first-line therapy in most patients with advanced NSCLC without a driver mutation, and “it may also increasingly be favored in combination with chemotherapy (and possibly bevacizumab) in patients with NSCLC harboring an EGFR mutation, and perhaps those with an ALK rearrangement as well.” As a result, more trials are needed to determine whether anlotinib provides benefit in a more modern patient population. 

“Anlotinib will need to demonstrate efficacy in patients who have previously received and progressed on an immune checkpoint inhibitor, chemotherapy for those patients without a driver mutation; and also, after initial targeted therapy for those patients with a cancer harboring a driver mutation for which there is a biomarker-directed therapy,” Dr West said.

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Conclusions

Dr West commented that although the results of the ALTER 0303 trial are “very provocative, they are limited by being conducted only in China, where there are significant differences in practice patterns and the patients themselves.” He said that additional studies with anlotinib should be pursued in other parts of the world “to clarify whether similar benefits are seen in other patient populations, particularly those who have previously been treated with prior chemotherapy and immunotherapy … and in patients with EGFR mutation-positive NSCLC who have previously received osimertinib, as [this] is the new standard of care as first-line treatment in the US.”

Reference

  1. Han B, Li K, Wang Q, et al. Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non–small cell lung cancer: the ALTER 0303 phase 3 randomized clinical trial[published August 9, 2018]. JAMA Oncol.doi: 10.1001/jamaoncol.2018.3039