Thomas Eldridge Stinchcombe, MD
Immunotherapy has demonstrated efficacy in the non–small cell lung cancer (NSCLC) treatment paradigm, both as a single agent and in combination with chemotherapy.
Thomas Eldridge Stinchcombe, MD, a professor of medicine and member of Duke Cancer Institute, recapped some of these data with immunotherapy as a single agent and in combination in NSCLC and what challenges the field is facing in 2018.
OncLive: What are the significant data with frontline pembrolizumab and chemotherapy in the KEYNOTE-189 trial?
The KEYNOTE-189 trial builds upon [cohort G] of the KEYNOTE-21 trial, which was a phase II trial that randomized patients to carboplatin/pemetrexed alone or carboplatin/pemetrexed with pembrolizumab. The phase II trial showed a robust response rate, PFS, and a trend toward OS. What we know at this time is that the phase III trial met the statistically significant improvement in PFS and OS. This serves as a confirmatory [study] to the promising results observed in the phase II trial.
What are some other combination regimens that are showing promise?
As for other combinations being developed with immunotherapy, the one that is furthest in development is the trial of carboplatin, paclitaxel, and bevacizumab alone or with atezolizumab. We saw this comparison of this 3-arm trial show promising improvement in response and a statistically significant improvement in PFS. The OS data are immature at this time.
Durvalumab is also garnering some interest in the field. Can you discuss the data from the PACIFIC trial?
The PACIFIC trial randomized patients with stage III NSCLC to either durvalumab for 1 year or placebo. This trial showed a statistically significant improvement in response rate, as well as improvement in PFS, which was statistically significant in a difference of about 11 months. These are very promising results, because the treatment for stage III disease has remained unchanged for 20 or 30 years before this trial.
The next steps are to build upon durvalumab or single-agent immunotherapy, try to identify which patients are most likely to benefit [from that], and further investigate and observe the OS benefit—which is still pending.
Are there any predictive markers yet?
That is kind of the debate in the field; do you give this to everyone? It’s 1 year of therapy. We would like to be able to see who will benefit, but right now we give it to everyone.
If a patient develops resistance to immunotherapy, what are the next steps?
With the success of immunotherapy in the first- and second-line settings, one of the challenges that we now face is what to do with those patients who have progressed on immunotherapy. Clinically, there are many different types of progression on immunotherapy, including the patients who never responded, to patients who maybe had stable disease for 6 or 9 months, and then progress. This is an area of active investigation looking at novel immunotherapy combinations.
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