On Friday, February 16, 2018, the FDA approved durvalumab (IMFINZI ®, AstraZeneca), an anti-PD-L1 checkpoint immunotherapy, for patients with unresectable, stage III non-small cell lung cancer (NSCLC) that hasn’t progressed after prior chemo-radiation treatment. Importantly, this approval covers patients regardless of their PD-L1 expression status.
While immunotherapies that target the PD-1/PD-L1 pathway are already approved to treat metastatic lung cancer, this approval now allows patients with non-metastatic lung cancer to receive immunotherapy, at least those whose tumors can’t be removed surgically.
In the absence of surgery, these patients are typically treated with a combination of chemotherapy and radiation, but oftentimes the cancer continues to grow. Fortunately, in results from a randomized clinical trial that the FDA based its approval on, durvalumab was found to significantly delay this cancer progression.
"Until now, treatment guidelines have recommended that patients with unresectable stage III lung cancer undergo a period of active surveillance following chemoradiation therapy until disease progression. Given that up to 89% of patients will progress to metastatic disease, it is important that there is now a new option that can give patients more time without disease progression,” according to Scott J. Antonia, M.D., Ph.D., of the H. Lee Moffitt Cancer Center, a CRI clinical team leader who was also an investigator on the durvalumab trial as well as the first author on the paper detailing its results. “[This] will change how we treat these patients."
Among the immunotherapy-treated patients, the median progression-free survival time was 16.8 months, compared to 5.6 months in the group that received only chemotherapy and radiation. In other words, while half of the non-immunotherapy-treated patients’ tumors began to grow again within six months, half of those who received immunotherapy remained stable or in remission for almost one year and five months. Additionally, at the 18 month mark, 44.2% of the immunotherapy-treated patients still had not experienced disease progression, compared to only 27.0% of the patients who didn’t receive immunotherapy.
This approval highlights an important step for lung cancer immunotherapy, and especially anti-PD-1 /PD-L1 checkpoint immunotherapy, which helps prevent cancer-targeting T cells from becoming “exhausted” and thus enables them to effectively attack tumors.
As mentioned previously, three anti-PD-1/PD-L1 immunotherapies—atezolizumab (TECENTRIQ ®, Genentech), nivolumab (Opdivo ®, Bristol-Myers Squibb), and pembrolizumab (Keytruda ®, Merck)—are already approved for patients with lung cancer that has metastasized, or spread to other organs, including as a frontline option.
However, in general it’s believed that the earlier a patient’s cancer is detected and treated, the more likely a patient is to survive long term. So while it’s remarkable that this approach has been able to provide such meaningful benefits even for patients whose disease has already spread, this most recent approval—which enables patients to be treated at an earlier stage of tumor progression—has the potential to make an even bigger impact on patient survival, although the actual impact of this approach on long-term overall survival remains to be seen.
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