Targeted Therapies Extend Overall Survival in Patients with Stage 4 ALK-Positive Lung Cancer

Half of patients diagnosed with stage 4, ALK-positive non-small cell lung cancer (NSCLC) from 2009 and 2017 were alive 6.8 years after diagnosis compared with just 2 percent of those diagnosed between 1995 and 2001 alive for five years, highlighting the importance of good targeted therapies, according to study findings published in the Journal of Thoracic Oncology.

“(Our study) illustrates the benefit of targeted therapy and selecting therapy for a specific genetic makeup,” first author Jose Pacheco, M.D., an assistant professor of medicine/medical oncology at Colorado University School of Medicine, said in an interview with CURE.

The study included 110 patients who had been treated at UCHealth University of Colorado Hospital between 2009 and 2017. They were a median age of 53 years and 83 percent had never smoked.

All but five patients were initially treated with Xalkori (crizotinib), an ALK inhibitor. Once the cancer had progressed, 78 percent were then given another ALK inhibitor — Alunbrig (brigatinib), Alecensa (alectinib) or Zykadia (ceritinib).

Patients who were diagnosed before 2010 typically received pemetrexed-based chemotherapy before receiving an ALK inhibitor, Pacheco explained, and whether this type of chemotherapy was given before or after an ALK inhibitor did not affect overall survival. However, the researchers found that patients who were on the pemetrexed-based therapy longer fared better, showing a 7 percent decrease in the risk for death with each additional month of the therapy.

“For ALK- and ROS1-positive tumors, pemetrexed therapy has shown better responses in patients with those specific genetic fusions as opposed to other molecular subtypes of lung cancer,” he said. “We don’t know exactly what it is about the biology of ALK-positive lung cancer, but it does appear to respond better.”

The researchers also learned that the number of organs where the cancer had spread at the time of diagnosis worsened survival outcomes. Interestingly, brain metastases at the time of diagnosis did not predict shorter survival.

“Newer ALK inhibitors have very good responses in both the body and the brain, and sometimes responses in the brain with these newer medications can even be better than in the body,” Pacheco said. “Crizotinib works well in the body but it doesn’t get into the brain very well. In the past, brain metastasis did influence outcomes but now that we have medications that get into the brain and elicit antitumor response, we have seen that to not be the case anymore.” Patients are also followed closely with MRIs or surveillance scans every three to four months, he added.

“I think the biggest thing is that (patients) can live quite a long time and, in many cases, live a productive, enjoyable life on these treatments,” Pacheco said. “When people are newly diagnosed, they think they have a limited time to survive, which is not necessarily the case. They think they will have to get chemotherapy and that it will make them feel sick or lose their hair.”

“(What this study) illustrates is that if you’re diagnosed you should make sure (your health care team) is doing appropriate molecular testing, and if you have a particular molecular abnormality, make sure you get the appropriate therapy for that,” he added.