A second, recent success story for targeted treatment involves the ALK fusion mutation, a genetic profile of tumors responsive to crizotinib. Results from phase I and II studies showed that crizotinib improved progression-free survival and overall survival in patients with tumors that had an ALK mutation; phase III studies are in progress.
"Patients with tumors that depend on these drivers have significantly better clinical outcomes when treated with specific inhibitors," Dr. Varella Garcia said.
This year’s meeting featured three main themes for patient management, but ultimately all three boil down to molecular biomarkers and molecularly directed treatment, Dr. Gandara said. One main theme – histologic profiles of advanced lung cancer – has been an important focus, but "histology is a transient selection method," he said. "At best, histology is a crude molecular selection device" superseded by molecular profiling itself.
Another important, recent focus has been maintenance therapy, but "the real questions are who gets further treatment after platinum-based induction, and when should they get it," questions best answerable by molecular profiling, he added.
"We have many ‘druggable’ molecular targets," Dr. Gandara noted.
"For almost every mutation [of the 10 genes that] the consortium is testing, we have phase I treatment trials underway," said Dr. Varella Garcia. Patients with tumors that carry KRAS and MEK mutations receive an investigational MEK inhibitor. Patients with tumors that contain HER2 mutations receive trastuzumab (Herceptin) as an investigational agent. Patients with MET mutations receive a MET monoclonal antibody.
Despite success so far, and pervasive optimism that current studies will validate new treatments, researchers cautioned that the management of advanced lung cancer also has some critical, unavoidable limitations.
"We will never cure advanced lung cancer; we can make it a chronic disease," Dr. Varella Garcia said. Effective treatment means that patients’ quality of life improves, and their disease comes under control for several years. But "it is almost universal that these patients with eventually progress again. We cannot cure advanced lung cancer. We can control it with new, targeted treatments that use oral drugs with low toxicity."
Dr. Gandara, Dr. Johnson, and Dr. Herbst disclosed relationships with numerous pharmaceutical and biotechnology companies. Among these, Dr. Johnson listed stock in Celgene and a patent for EGFR testing by Genzyme. Dr. Varella Garcia said that she has been a consultant to Abbott.