Renato G. Martins, MD, MPH
As the class of agents targeting the PD-1/PD-L1 pathway expands in non–small cell lung cancer (NSCLC), so does the potential population of patients who would be candidates for the groundbreaking immunotherapy, according to leading experts in the field.
Less than a year after the first agent gained the FDA’s approval in NSCLC, systemic immune checkpoint therapy has become the top choice for second-line therapy for patients with metastatic disease that does not harbor mutations for which there are molecularly targeted drugs.
In fact, patients with negative expression levels for the PD-1 ligand, PD-L1, demonstrate response rates to checkpoint inhibitors that compare favorably with the experience of patients who are treated with second-line chemotherapy without the attendant toxicities.
The optimal use of the approved and emerging checkpoint agents was a central theme of the 10th Annual New York Lung Cancer Symposium® that Physicians’ Education Resource (PER®) hosted November 7 in New York City.
“As of now, I don’t think that any patient is clearly not a candidate for these drugs,” said Renato G. Martins, MD, MPH, the medical director for thoracic/head and neck oncology at Seattle Cancer Care Alliance, in an interview. “Every patient with non–small cell lung cancer would potentially be a candidate in the second-line setting.”
Roman Perez-Soler, MD, who served as a program chair for the PER meeting, expressed excitement and confidence about the potential for the PD-1/PD-L1 pathway agents to go beyond shrinking tumors and deliver long-term survival for a subgroup of patients with NSCLC.
“The dream here—and what would make a big difference—is the possibility that a small group of patients with stage IV non–small cell lung cancer can actually be cured,” said Perez-Soler, who chairs the Department of Oncology at Montefiore Medical Center and is deputy director of the Albert Einstein Cancer Center in Bronx, New York.
Rapidly Changing Landscape
It has been 3½ years since the concept of targeting the PD-1 immune checkpoint pathway was introduced at the American Society of Clinical Oncology Annual Meeting in early research findings that involved nivolumab (Opdivo) in several advanced tumor types, including NSCLC.
Martins said those findings, along with research into EGFR mutations in NSCLC and a report on CT screening for high-risk patients that were released within days of each other, marked three of the most important days for lung cancer treatment.
In terms of immunotherapy advances, “the big breakthrough really was the recognition that non–small cell lung cancer could be a disease treated by immune therapy,” Martins said.
Since then, the PD-1 inhibitors nivolumab and pembrolizumab (Keytruda) have gained FDA approvals in melanoma and NSCLC. In late November, nivolumab also was approved for patients with advanced renal cell carcinoma.
Nivolumab was initially approved in March 2015 for the treatment of patients with metastatic squamous NSCLC with progression on or after platinum-based chemotherapy. In October, the FDA expanded the indication to include patients with progression on or after platinum-based chemotherapy with nonsquamous histologies.
Also in October, pembrolizumab was approved for patients with metastatic NSCLC with progressive disease after platinum-containing chemotherapy with a key difference.
A key difference between the approvals for the two drugs is that the label for pembrolizumab specifies that it is indicated for patients whose tumors express PD-L1 as measured by a companion diagnostic, which thus far is the PD-L1 IHC 22C3 pharmDx test. For nivolumab, there is a complementary test, the PD-L1 IHC 28-8 PharmDx assay, that is not required to use the drug.
Additionally, two agents targeting PD-L1, atezolizumab (MPDL3280A) and durvalumab (MEDI4736), are advancing in clinical development. The FDA has designated atezolizumab as a breakthrough therapy for the treatment of patients with PD-L1–positive NSCLC, meaning the agency will expedite its review. Durvalumab is being evaluated under a fast track designation for patients with NSCLC who have received 2 prior systemic treatments.
As far as Perez-Soler is concerned, clinical trial results thus far support the use of PD-1 inhibitors as the first choice for second-line therapy “based on efficacy across the board and lower toxicity.”
“Patients typically progress in two or three months,” Perez-Soler said in an interview. “The initial drugs, typically chemotherapy, shrink the tumor but then it comes back and the same drug cannot kill it.