Leora Horn, MD, MSc, associate professor of cancer research, Vanderbilt University Medical Center, discusses updates in lung cancer presented at the 2019 ASCO Annual Meeting.
In patients with newly diagnosed advanced non—small cell lung cancer (NSCLC), 23.2% of patients were alive at 5 years with single-agent pembrolizumab (Keytruda), according to updated data from the phase Ib KEYNOTE-001 study. In patients who were previously treated, the 5-year overall survival (OS) rate was 15.5%. Historically, 5-year the OS rate in advanced NSCLC was around 5%.
These data mirror what was seen in the CheckMate-003 study, which showed that at 5 years, 16% of patients treated with nivolumab (Opdivo) monotherapy were still alive. Horn says this suggests that when checkpoint inhibition works in these patients, it induces durable responses.
Three-year OS data from the phase III PACIFIC trial, which looked at durvalumab (Imfinzi) following concurrent chemoradiation in patients with stage III unresectable NSCLC, were also encouraging. The survival advantage for the PD-L1 inhibitor over placebo is important because physicians are still aiming to cure patients in the stage III setting, Horn notes. As such, durvalumab has become the standard of care in the United States in this space for patients who do not progress following chemoradiation.
The phase III RELAY trial also generated excitement at the 2019 ASCO Annual Meeting. The study showed that adding ramucirumab (Cyramza) to erlotinib (Tarceva) reduced the risk of disease progression or death by 40% compared with erlotinib alone in patients with EGFR-positive NSCLC. At a median follow-up of 20.7 months, the median progression-free survival (PFS) was 19.4 months with the combination compared with 12.4 months with erlotinib alone (HR, 0.591; 95% CI, 0.461-0.760; P <.0001).
However, there are important considerations for this type of combination, Horn says. Ramucirumab is given intravenously and in combination with an oral agent, so patients would have to come to the clinic more often.
A take-home message from the meeting was that all patients with NSCLC should be tested for molecular abnormalities because even the rarer mutations are starting to be matched with targeted therapy, Horn says. For example, for patients with MET exon 14 skipping mutations, there are 2 active agents in development. Tepotinib has induced a median PFS approaching 12 months. Drugs for patients with RET fusions and KRAS mutations may also be moving through the pipeline shortly, Horn predicts.