Lung cancer studies demonstrate incremental progress


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While non-small cell lung cancer (NSCLC) has a reputation as a hard-to-treat cancer, several studies presented at ASCO may help researchers decide on the best treatment for individual patients, as well as uncovering possible new treatments for a type of NSCLC that hasn't benefited from the recent targeted therapy frontier.On the heels of its Food and Drug Administration approval for gastric cancer, ramucirumab also has promise in NSCLC, as shown by the recently announced results of the REVEL study.Researchers enrolled 1200 patients with NSCLC that had progressed on platinum-based chemotherapy. Typical second-line therapy for NSCLC includes docetaxel, Alimta (pemetrexed) and the targeted agent, Tarceva (erlotinib), which is reserved for patients with EGFR-mutated lung cancer. Unfortunately, these second-line treatments have limited use and median survival with them is around seven to months months. In the study, patients who received ramucirumab with standard docetaxel lived a median of 10.5 months compared with patients receiving docetaxel alone (9.1 months). Study researchers noted that while the survival is incremental, this is the first trial that has shown a survival advantage in second-line therapy for NSCLC. No surprising toxicities arose, but severe cases of neutropenia, fatigue, pneumonia and hypertension were reported during the study. Ramucirumab is an angiogenesis inhibitor, much like Avastin (bevacizumab), which is also approved for lung cancer, but as a first-line therapy. This class of drugs, which target VEGF (vascular endothelial growth factor), blocks blood vessel growth to the tumor and can carry a risk of bleeding issues.Jyoti Patel, a lung cancer specialist at the Robert H. Lurie Comprehensive Cancer Center in Chicago, says that while the median survival was only a month and a half, patient response to the treatment was over a wide range. "There are certainly patients that benefit more when you look at the wide bell-shape curve." Unfortunately, strategies to identify patients that would respond to VEGFR-targeted agents, such as ramucirumab have been unsuccessful. "We don't have a biomarker. It's been looked at for bevacizumab, and there are certainly efforts underway to find biomarkers, but it's not a single aberration."In one of the largest study ever conducted in squamous cell lung cancer, necitumumab, an investigational agent that targets the EGFR mutation in certain lung cancers, did improve survival, albeit modestly.The drug was tested in 1,092 patients with stage 4 squamous cell NSCLC. Patients who received necitumumab with standard chemotherapy had longer median survival (11.5 months compared with 9.9 months with standard chemotherapy). Progression-free survival was also slightly better with the agent. Because there are few options for this type of NSCLC, the company is expected to file necitumumab for approval by the end of the year. "Squamous cell lung cancer, although it accounts for less than half of patients with NSCLC, we have not made significant inroads," Patel says. "Every time we see a patient with this type of lung cancer, they are so hungry for options." And while the survival advantage was not what she had hoped, she says it's something. "There are gains, but they are small."In early-stage lung cancer, a study examined Tarceva (erlotinib) in patients with non-metastatic NSCLC after surgery. While the treatment is approved for metastatic disease, experts wondered if the drug would help prolong disease-free survival and stave off recurrence. While results show that the use of Tarceva in this setting did not extend disease-free survival, further studies in EGFR mutation-positive patients are ongoing, which may reveal benefit in this group of individuals. Another study also examined the combination of Avastin and Tarceva in metastatic NSCLC. While this study had positive results, experts questioned if the Japanese-based trial would translate into the same benefit to Western patients.

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