Role of Postoperative Radiotherapy in NSCLC

Kristen Marrone, MD, discusses the evolving role of postoperative radiotherapy in early-stage non–small cell lung cancer (NSCLC) and ongoing trials examining the use of immunotherapy and targeted agents in patients with unresectable stage III disease.

The use of postoperative radiotherapy (PORT) appears to have diminished clinical relevance in the treatment of patients with early-stage non–small cell lung cancer (NSCLC), while immunotherapy and TKIs are changing the way disease control is discussed in those with unresectable stage III disease, according to Kristen Marrone, MD.

“[We have seen] so much evolving data regarding best [approaches] for each individual patient, particularly [with regard to] the use of radiation following surgery” Marrone said. “The biggest excitement for us is that the use of immunotherapy with durvalumab [Imfinzi] has greatly improved OS for those patients who had unresectable lung cancer following chemotherapy and radiation.”

Although historically, PORT has been a standard approach in the setting of R1 or R2 resection, positive margins, surprise pN2 disease, and patients with pN1 disease who can’t receive adjuvant chemotherapy,¹ when examined in the phase 3 LungART trial (NCT00410683), this approach failed to significantly improve disease-free survival (DFS) vs no PORT.² The median DFS in the investigative and control arms was 30.5 months vs 22.8 months, respectively (HR, 0.58; 95% CI, 0.67-1.07; P = .16).

Additionally, data from the phase 3 PACIFIC trial (NCT02125461) supported the rationale to use checkpoint inhibitors after chemoradiation. Here, the use of durvalumab (Imfinzi) was found to improve median OS over placebo, at 47.5 months vs 29.1 months, respectively (HR, 0.71; 95% CI, 0.57-0.88).³

Now, investigators are examining the concurrent use of durvalumab and chemoradiation vs chemoradiation alone in patients with unresectable stage III NSCLC as part of the phase 3 PACIFIC-2 trial (NCT033519971), and the efficacy of osimertinib (Tagrisso) as maintenance therapy following chemoradiation in patients with stage III, unresectable EGFR-mutant disease, as part of the phase 3 LAURA trial (NCT03521154).

In an interview with OncLive® during a 2021 Institutional Perspectives in Cancer webinar on lung cancer, Marrone, the associate program director for the Hematology/Medical Oncology Fellowship Program, and an assistant professor of oncology at Johns Hopkins School of Medicine, discussed the evolving role of PORT in early-stage NSCLC and ongoing trials examining the use of immunotherapy and targeted agents in patients with unresectable stage III disease.