A number of patients with lung cancer have benefitted from immunotherapy agents, and researchers in the field are excited that these treatments will continue to improve the field.
Currently, the checkpoint inhibitors Opdivo (nivolumab), Keytruda (Keytruda) and Tecentriq (Tecentriq) are approved for the second-line treatment of patients with non–small cell lung cancer (NSCLC). Keytruda is FDA approved in the frontline setting, as well.
During a recent presentation, Lawrence E. Feldman, M.D., 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.
Can you discuss your presentation on checkpoint inhibitors in NSCLC?
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 Keytruda in patients who express more than 50 percent of PD-L1 expression on their tumors.
In the second-line setting, we now have Keytruda, Opdivo and Tecentriq as monotherapy for patients with NSCLC. We now also have a first-line positive result with carboplatin, pemetrexed, and Keytruda for patients with NSCLC.
Could you go into detail on some of these trials that have been particularly impressive?
In the second-line setting, we have the CheckMate-017 and CheckMate-057 [Opdivo] 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 Keytruda in the second-line setting. Those patients must have some PD-L1 expression in order to receive second-line treatment with Keytruda. Then, we have Tecentriq and the benefit with that was demonstrated in the OAK trial, which involved over 800 patients.
Therefore, we have three different immunotherapy agents to offer patients in the second-line setting. Opdivo is given once every two weeks, and Keytruda and Tecentriq are both given once every three weeks. Tecentriq is an anti–PD-L1 agent, while Opdivo and Keytruda are anti–PD-1 agents.
Do you have any insight on the potential for Imfinzi (durvalumab)?
Imfinzi development is very exciting, especially in the stage 3 setting. There are good data emerging showing consolidation therapy after chemoradiation with Imfinzi, 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 Imfinzi in my practice, especially in the stage 3 setting where it seems to be very beneficial.
What significant challenges still exist in utilizing checkpoint inhibitors in NSCLC?
As Dr Jyoti Patel discussed, and as exciting as this field is, only about one in five 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.
Imfinzi 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 two of them shows lot of promise. [The same can be said for] Opdivo and Yervoy (ipilimumab). Those are two combinations making their way through various phase 3 trials and may soon lead to approvals. We also have a phase 1/2 trial with Keytruda and another immunomodulatory agent, which is accruing patients as we speak.
What are some major takeaways you'd like to mention?
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.