Roy H. Decker, MD, PhD, a professor of Therapeutic Radiology; vice chair for Clinical Research, Therapeutic Radiology; director of the Clinical Trials Office; and associate cancer center director, Clinical Sciences at Yale Cancer Center, discusses the use of pembrolizumab (Keytruda) with concurrent chemoradiotherapy in patients with inoperable, locally advanced non–small cell lung cancer (NSCLC).

The standard of care for patients with inoperable, locally advanced disease has been chemoradiation followed by the checkpoint inhibitor durvalumab (Imfinzi), since the phase 3 PACIFIC trial (NCT02125461), according to Decker, who is also the Disease Aligned Research Team Leader, Therapeutic Radiology, and associate director of the Residency Training Program, Therapeutic Radiology.

In a phase 1 study (NCT02621398), a checkpoint inhibitor was added incrementally earlier in the treatment course. In the final cohort, patients received weekly carboplatin and paclitaxel with concurrent radiation and started full dose pembrolizumab on the first day, which was received concurrently with chemoradiation, Decker says. Pembrolizumab was also administered in the adjuvant setting.

This was one of the first studies that demonstrated feasibility in moving the checkpoint inhibitor earlier in therapy where it could have an even greater benefit in patients with NSCLC, Decker concludes.

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Roy H. Decker, MD, PhD, discusses the use of pembrolizumab with concurrent chemoradiotherapy in patients with inoperable, locally advanced non–small cell lung cancer.


Dr. Decker on Pembrolizumab With Concurrent Chemoradiotherapy in Inoperable Locally Advanced NSCLC

Roy Decker, MD, PhD, associate professor of Therapeutic Radiology, Yale Cancer Center, discusses traditional roles of radiation therapy in the treatment of patients with lung cancer.

This longstanding modality has several distinct roles in the current treatment landscape, Decker says. For example, patients with stage I lung cancer are treated with stereotactic body radiation when they are deemed inoperable or ineligible for curative surgery. For those with locally advanced disease, the standard of care is to give chemotherapy and radiation concurrently with curative intent. Some patients also receive chemoradiation in the adjuvant setting, after an attempt at curative surgical resection, Decker adds.

For patients with stage IV metastatic disease, radiation is typically used in a palliative role, as a way to limit pain from bone or central nervous system metastases. With the emergence of effective therapies in the metastatic setting, the management of metastatic disease becomes more important, Decker notes. A newly critical indication for radiation therapy is in oligometastatic disease—patients who have metastases, but at limited sites.

Dr. Decker on Distinct Roles of Radiation in Lung Cancer

Roy Decker, MD, PhD, associate professor of Therapeutic Radiology, Yale Cancer Center, discusses common adverse events (AEs) associated with radiation therapy in the treatment of patients with lung cancer.

For patients with stage III lung cancer who are receiving the standard 6 weeks of chemoradiation, the major dose-limiting toxicity is esophagitis, which causes difficulty or pain when swallowing. This toxicity is what limits the ability of the patient to make it through their treatment course.

In the long term, however, Decker says that radiologists are more concerned with pneumonitis—inflammation or fibrosis of the lungs. In addition, recent studies have suggested that radiation therapy might have a role in causing cardiac issues in patients. Researchers found that even low doses of radiation to the heart can increase the risk of cardiac toxicity even up to 3 years after treatment is stopped.

Roy Decker, MD, PhD, associate professor of Therapeutic Radiology, Yale Cancer Center, discusses common adverse events associated with radiation therapy in the treatment of patients with lung cancer.

Dr. Decker Discusses AEs Associated With Radiation in Lung Cancer

Roy Decker, MD, PhD, associate professor of Therapeutic Radiology, Yale Cancer Center, discusses the current role of radiation therapy in the treatment of patients with non—small cell lung cancer (NSCLC).

Due to the rise of more effective therapies than in previous years, patients are living longer, thus making the management of metastatic disease more important, Decker says. One of the newest indications for radiation is for patients with oligometastic disease—patients who have metastases at diagnosis or after therapy, but with limited sites of disease. Recent studies have shown a survival benefit when adding radiation, surgery, or ablative techniques to a limited number of metastatic sites, when patients have oligometastases, after first-line chemotherapy.

With immunotherapy and targeted agents, physicians are seeing patients recur at isolated sites of disease. These are patients who had several sites of metastases, but are now progressing in 1 or disease locations, Decker says. Aggressive local radiation is an option here, Decker says, so patients can continue to benefit from the systemic therapy they are responding to in other areas.

Roy Decker, MD, PhD, associate professor of Therapeutic Radiology, Yale Cancer Center, discusses the current role of radiation therapy in the treatment of patients with non–small cell lung cancer.

Dr. Decker on Current Role of Radiation in NSCLC

Roy Decker, MD, PhD, associate professor of Therapeutic Radiology, Yale Cancer Center, discusses stereotactic body radiation therapy (SBRT) as a treatment for patients with lung cancer.

Although SBRT has only been around for about 20 years, it is rapidly becoming a standard of care approach for patients with early-stage non—small cell lung cancer (NSCLC) who are not eligible for surgery, says Decker.

A number of attempts to initiate randomized trials comparing the efficacy of SBRT with surgery have failed, mainly due to poor accrual. Currently, a large consortium trial is underway comparing lobectomy with SBRT for patients with early-stage NSCLC who are at a borderline risk for surgery.

Roy Decker MD, PhD

Articles

Dr. Decker on Pembrolizumab With Concurrent Chemoradiotherapy in Inoperable Locally Advanced NSCLC

Dr. Decker on Distinct Roles of Radiation in Lung Cancer

Dr. Decker Discusses AEs Associated With Radiation in Lung Cancer

Dr. Decker on Current Role of Radiation in NSCLC

Dr. Decker on Stereotactic Body Radiation Therapy in Lung Cancer