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Lawrence E. Feldman, MD, discusses first- and second-line therapy with checkpoint inhibitors in NSCLC, and the promise that emerging combinations could have on the field.
Lawrence E. Feldman, MD
Immunotherapy has excited researchers in the field of oncology over the past few years, and a portion of patients with lung cancer have had significant benefits from this therapeutic option.
Currently, the checkpoint inhibitors nivolumab (Opdivo), pembrolizumab (Keytruda), and atezolizumab (Tecentriq) are approved for the second-line treatment of patients with non—small cell lung cancer (NSCLC). Pembrolizumab is FDA approved in the frontline setting, as well.
During his presentation on checkpoint inhibitors in NSCLC at the 2017 OncLive® State of the Science SummitTM on Advanced Non—Small Cell Lung Cancer, Lawrence E. Feldman, MD, provided his expertise on the use of these PD-1/PD-L1 inhibitors and the impact they have had on clinical practice.
“It is an exciting time in lung cancer treatment with all of these new agents and we are happy to have immunotherapy be a part of lung cancer treatment for many years now,” said Feldman.
In an interview during the meeting, Feldman, associate professor, Section of Hematology/Oncology, College of Medicine, the University of Illinois Hospital and Health System, discussed first- and second-line therapy with checkpoint inhibitors in NSCLC, and the promise that emerging combinations could have on the field.Feldman: I was asked to speak on first- and second-line immunotherapy in lung cancer, as well as third-line and beyond. I reviewed the various trials that led to the FDA approval of first-line therapy, such as pembrolizumab in patients who express more than 50% of PD-L1 expression on their tumors.
In the second-line setting, we now have pembrolizumab, nivolumab, and atezolizumab as monotherapy for patients with NSCLC. We now also have a first-line positive result with carboplatin, pemetrexed, and pembrolizumab for patients with NSCLC.In the second-line setting, we have the CheckMate-017 and CheckMate-057 [nivolumab] trials. CheckMate-017 is for patients with squamous cell carcinoma and CheckMate-057 is for nonsquamous NSCLC. Then, we have the KEYNOTE-010 trial, which is of pembrolizumab in the second-line setting. Those patients must have some PD-L1 expression in order to receive second-line treatment with pembrolizumab. Then, we have atezolizumab and the benefit with that was demonstrated in the OAK trial, which involved over 800 patients.
Therefore, we have 3 different immunotherapy agents to offer patients in the second-line setting. Nivolumab is given once every 2 weeks, and pembrolizumab and atezolizumab are both given once every 3 weeks. Atezolizumab is an anti—PD-L1 agent, while nivolumab and pembrolizumab are anti–PD-1 agents.Durvalumab development is very exciting, especially in the stage III setting. There are good data emerging showing consolidation therapy after chemoradiation with durvalumab, which is very promising. It was also announced that there was an improvement in overall survival. Therefore, that is very exciting and we look forward to starting durvalumab in my practice, especially in the stage III setting where it seems to be very beneficial.As Dr Jyoti Patel discussed, and as exciting as this field is, only about 1 in 5 patients will experience long-term benefit with monotherapy. We are looking at various combinations of immunotherapy agents to help improve response rates. The most challenging area now is finding out which combinations will improve outcomes in these patients.
Durvalumab and tremelimumab as a combination is an exciting area, as you have an anti—PD-L1 agent as well as an anti–CTLA-4 agent. Combining the 2 of them shows lot of promise. [The same can be said for] nivolumab and ipilimumab (Yervoy). Those are 2 combinations making their way through various phase III trials and may soon lead to approvals. We also have a phase I/II trial with pembrolizumab and another immunomodulatory agent, which is accruing patients as we speak.I just hope that they gained additional information about how to use immunotherapy in an appropriate setting and how to manage the side effects. Also, [we should] encourage them to have a dialogue with people who specialize in lung cancer, and that will hopefully be mutually beneficial to the academic people that try to specialize in lung cancer and those in the community that see all different types of cancers. I am happy to have a dialogue with any community oncologist; these discussions can only help and benefit our patients.