Ashley A. Weiner, MD, PhD
Although the standard of care for patients with stage III unresectable non–small cell lung cancer (NSCLC) has been concurrent chemoradiotherapy at 60 Gy at 2 Gy/fraction, the addition of immunotherapy for those who have not progressed on chemoradiotherapy can offer an increased benefit, explains Ashley A. Weiner, MD, PhD.
Results of the phase III PACIFIC trial showed that, regardless of PD-L1 status, patients with locally advanced, unresectable stage III NSCLC responded to the PD-L1 inhibitor durvalumab (Imfinzi). Objective response rate, as assessed by blinded independent central review, was also significantly higher with durvalumab (28.4% vs 16.0%; P
“It has been shown that there is some immune response— some innate release of immune markers in response to radiation in lung cancer and other disease sites that can help immunotherapy efforts—and that is really empowering,” says Weiner.
Proton radiotherapy has also been emerging in the field. While Weiner explains that it has many potential benefits, such as sparing the contralateral lungs and heart, there are challenges with its use in NSCLC.
In an interview during the 2018 OncLive®
State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Weiner, assistant professor, Department of Radiation Oncology, University of North Carolina (UNC) at Chapel Hill School of Medicine, UNC Lineberger Comprehensive Cancer Center, discussed the expansions and limitations of radiotherapy in patients with NSCLC and ongoing efforts to enhance administration and efficacy.
OncLive®: Can you speak to the use of radiotherapy in patients with NSCLC?
: We are currently treating locally advanced or stage III lung cancer at 2 Gy/fraction at 60 Gy, and we’ve been doing that for a while. It’s safe and effective, but we’re looking to see if there is a more convenient and more efficacious approach for patients. We’re looking at ways to safely increase doses; some of these have been limited thus far with negative studies. Nonetheless, we’re investigating ways to administer higher doses per fraction, or use hypofractionation.
Can stereotactic body radiation boosts enable dose escalation?
It’s possible. There is a study run out of a single institution but opened at several institutions looking at that. It’s not something I would do off of a protocol. In that study, they found what they would claim to be the maximum-tolerated dose (MTD), but it hasn’t found its way into the standard of care yet.
How have the competing theories of radiation administration evolved?
A lot of people are still proponents of MTD. There is no evidence that exceeding 60 Gy at 2 Gy/fraction and potential fractionation is beneficial. You could perhaps go to 66 Gy, but in terms of reaching a higher MTD, you have to look at different strategies with some sort of boost or hypofractionation.
It would be very difficult to study a lower radiation dose unless it was a higher dose/fraction so that it was biologically equivalent. For example, it would be difficult to do a trial looking at 40 Gy using 2 Gy/fraction because that is not enough for a local control.
Can you discuss some clinical trials that have examined the use of radiotherapy in this patient population?
A lot of clinical trials have looked at the use of radiotherapy in stage III lung cancer. One of the first trials, RTOG 7301, examined the use of 60 Gy conformal radiotherapy. There was the CALGB 8433 trial, which facilitated the use of sequential chemotherapy with a platinum-based doublet, followed by radiation; this showed an overall survival benefit. In comparison with sequential chemotherapy radiation, the RTOG trial studied the addition of concurrent chemotherapy with radiation.
The next landmark trial was RTOG 0617, which was an earlier phase II trial examining the use of 74 Gy. There was no increase in toxicity, and outcomes were better than historical controls.