Luis Paz-Ares, MD
FORMAL DISCUSSANT of the ALEX and ALUR trials, Luis Paz-Ares, MD, Professor of Medicine at the Hospital Universitario 12 de Octubre, Madrid, said that the ALEX trial is “good news” for patients. “Importantly, 40% had baseline metastases. Disease progression was nicely controlled with alectinib [Alecensa], with the same magnitude of control in patients with and without brain metastases at baseline.”
He continued, “The incidence of brain progression without central nervous system (CNS) metastases at baseline compared with those who had baseline CNS disease is amazing. The same is true for those treated with or without prior radiation—magnificent,” Dr. Paz-Ares said.
“My conclusion for the ALEX trial is that alectinib results in better progression-free survival than crizotinib (Xalkori), particularly at the CNS level. Alectinib may be the preferred treatment option. It has better efficacy, better disease control in the CNS, and a favorable safety profile. Taken together, we don’t yet know the best sequence, but for most patients, alectinib should be the first treatment in the sequence,” he stated.
The phase III ALUR trial also had good results in the third-line setting, according to Dr. Paz-Ares. “About 33% of patients had brain metastases. Response rates were good, and duration of response was better than expected. Improvement in progression-free survival was amazing, with a hazard ratio of 0.15.”
Changing Paradigm
DR. PAZ-ARES SUGGESTED that phase II trials should be considered to move the field forward, so that patients can get the best treatment sooner rather than later.
“These results are coming late for third-line treatment,” he said.
“These treatments for ALK-positive disease are directed to a small subset of patients, which is a change in the paradigm of developing new drugs in the era of genomic medicine. In the near future, we will have to address how to get approval of drugs directed to very small subsets. Academic registries may be helpful in this regard,” he noted. ■
DISCLOSURE: Dr. Paz-Ares has received consultancy fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharpe & Dohme, Pfizer, Roche, Lilly, Boehringer Ingelheim, Novartis, and Ariad.
