Role of Surgery Could Change Following Durvalumab Approval for Stage III NSCLC

Benny Weksler, MD, FACS

The use of surgery remains pivotal for patients with stage I and II non—small cell lung cancer (NSCLC); however, surgeons are now less likely to resect tumors patients with stage III disease following the release of the results from the PACIFIC trial and other studies, says Benny Weksler, MD, FACS.

Though the FDA approval of durvalumab (Imfinzi)—which was based on the phase III data with PACIFIC—following chemoradiation is indicated for patients with unresectable disease, Weksler says surgery has become less of a go-to option for stage III disease and has been shown to be noninferior to chemoradiation.

However, minimally invasive approaches, robotic surgery, and the use of adjuvant therapy in stage II patients have garnered excitement in the surgical space, he adds.

OncLive: How is surgery impacted in the biomarker-driven era of NSCLC?

How is the role of surgery changing as more systemic regimens are being explored in clinical trials?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Advanced Non—Small Cell Lung Cancer, Weksler, chief, Division of Thoracic Surgery, professor of surgery, University of Tennessee Health Science Center, Eastridge- Cole Endowed Professor of Thoracic Surgery, West Cancer Center, tracked the use of surgery in a biomarker-driven and drug-dependent era and highlighted other cases in which surgery can benefit patients with NSCLC.Weksler: For most operable patients with lung cancer, biomarkers are not part of the decision-making process in taking patients to surgery.We are becoming more minimally invasive and working through small incisions. Up to this point, targeted therapy has not been shown to improve patient outcomes with stage I and II disease. The biggest thing that happened in the last year was the PACIFIC trial, which examined the monoclonal antibody durvalumab to the PD-L1 protein. The trial showed that patients with stage IIIA and IIIB disease had a very significant benefit from 1 year of administration of the antibody. In this group of patients, surgery is not going to be part of their treatment anymore.

What are some novel techniques or surgical approaches we have seen emerge in lung cancer?

Apart from stage IV and potentially stage III disease, are there any characteristics that would prevent a patient from undergoing surgery?

Is there any reason to use neoadjuvant therapy for these early-stage patients?

Having said that, it is also true that previous studies have consistently shown that surgery was not better than traditional chemotherapy and radiation for these patients. Surgery has lost some enthusiasm in that area, but there were patients we thought may benefit from surgery. Now, we are not likely going to operate on those patients very often.The main thing [was] the introduction of minimally invasive surgery around 2005 when it became more popular—initially as video-assisted thoracoscopy. More recently, we’ve seen robotic surgery for lung cancer. Both techniques have been shown to improve patient quality of life and decrease hospital stay and complications. All of a sudden, we’re able to operate on patients who were too frail to be operated on previously. This is something that has become way more popular in the last 10 years or so.Not in stage I and stage II disease. In stage I disease, surgery has a cancer-specific survival of about 85%, which underscores the need for lung cancer screenings. If we screen, we can find more patients in stage I and stage II disease than patients with distant metastasis or locally advanced regional disease, such as patients with IIIA and IIIB.Neoadjuvant therapy for stage I and stage II disease has not been shown to be productive. The initial approach for stage III disease was neoadjuvant therapy and then surgery. After the trials showed that chemotherapy and radiation and surgery were the same, a lot of practitioners ended up administering definitive chemotherapy and radiation. Surgery was reserved for a select few patients.

Adjuvant therapy is more relevant in patients with stage II disease. Selected patients with tumors that are larger than 4 centimeters in diameter are surviving longer with adjuvant therapy.

What challenges still exist with surgery?

So far, the data have only reflected adjuvant systemic, traditional chemotherapy. This will likely be an opportunity to look into specific markers to see if targeting those markers in patients with relatively early-stage lung cancer will show benefit of survival compared with traditional chemotherapy.Early detection is the main thing. Lung cancer is a disease that has received a relatively low amount of research dollars. We need to do more education and smoking cessation education in terms of screening for lung cancer. That’s what is going to improve survival in patients with lung cancer.