Uncertainty Surrounds Nondriver NSCLC Treatment After Progression

Caroline Seymour
Published: Friday, Nov 09, 2018

Hossein Borghaei, DO

Hossein Borghaei, DO, MS

Immunotherapy alone or in combination with chemotherapy has become the standard of care for those without oncogene-driven lung cancer; however, the decision upon progression is not as clear, explained Hossein Borghaei, DO, MS.

In August 2018, the FDA granted a full approval to the combination of pembrolizumab (Keytruda) and standard chemotherapy for patients with nonsquamous, non-oncogene driven non–small cell lung cancer (NSCLC) based on data from the phase III KEYNOTE-189 trial. Data showed a more than 50% reduction in the risk of death and an overall survival (OS) benefit irrespective of PD-L1 status.

However, patients who have ≥50% PD-L1 expression may also be candidates for single-agent pembrolizumab, which improved OS versus chemotherapy in the phase III KEYNOTE-024 trial.

Though patients who receive frontline immunotherapy can switch to a platinum doublet in the second-line setting, Borghaei explained that the options for patients who received an upfront combination of chemotherapy and immunotherapy are limited.

“We need to do more trials. Unless we're happy to go with old-fashioned docetaxel or other drugs, we're going to have to participate in studies,” Borghaei said in advance of his presentation at the 2018 New York Lung Cancers Symposium. “We're going to have to encourage everyone to seek out trials to figure out what the next best treatment option is for our patients.”

In an interview with OncLive, Borghaei, chief of thoracic medical oncology at Fox Chase Cancer Center, discussed current and potential therapeutic approaches for patients with non-oncogene driven lung cancer who progress on frontline treatment.

OncLive: You are presenting on subsequent therapies for non-oncogene driven lung cancer. What would you like to emphasize in that space?

Borghaei: The overwhelming data that we have for patients who do not have an oncogene-driven tumor suggest that a combination of chemotherapy plus immunotherapy or potentially single-agent immunotherapy is the standard of care. [Single-agent immunotherapy should only be considered in] certain patients, namely those with PD-L1 expression greater than 50%.

That raises the question of what to do in the second-line setting. In the case of a patient who has at least a 50% PD-L1 expression and has gotten single-agent immunotherapy, which is typically pembrolizumab, the choice is a little clearer. If they're clearly progressing on immunotherapy, the standard is to switch to chemotherapy because those patients have not seen a platinum doublet. The idea of continuing immunotherapy and adding chemotherapy has been raised. I can tell you that there will be a combined ECOG/SWOG national study with multiple arms that will address that specific issue. I'm the national principal investigator of the study, along with Dr Anne Chiang from Yale Cancer Center.

If the platinum doublets don’t work, and in the absence of clinical trials, you are back to docetaxel or any of the other drugs that are out there. That is not something that we want to go back to because we have experienced this “shiny new tool” of immunotherapy. We like the way it behaves, and we like the better quality of life patients have on it. We're hoping to develop other combination therapies that can overcome this immune resistance.

For patients who get chemotherapy plus immunotherapy and then have progression, the question is even more difficult. Again, you’re back to the old-fashioned docetaxel or docetaxel plus ramucirumab (Cyramza). The combination of docetaxel and ramucirumab, regardless of how small the improvement was, did show an improvement over docetaxel monotherapy. There is logic to want to use a combination that maximizes benefit. In the absence of clinical trials, it's hard to identify specific regimens that are going to be any different than what we've seen before. We're going back to docetaxel or gemcitabine.

I don't have any great insight to say, “If somebody is progressing through chemoimmunotherapy, you should absolutely use drug ‘X.’” I don't think anybody has a crystal ball to predict what is going to happen. It's an area that we need additional drug development in. We need to concentrate on the patients who are going to come off of chemoimmunotherapy. In my experience, these patients have a really good performance status. They're very interested in continuing treatments beyond that stage.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Advances in™ Therapies for Patients With ALK-Positive Lung Cancers: More Options…More Decisions…Better OutcomesAug 30, 20191.5
Oncology Briefings™: Treating Advanced NSCLC Without Actionable MutationsAug 30, 20191.0
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