ONCLIVE NEWS NETWORK: ON LOCATION WILL BE LIVE AT ESMO THIS WEEK - STAY TUNED FOR MORE INFORMATION!

Neoadjuvant Immunotherapy May Change Standard of Care in Early-Stage NSCLC

Wade T. Iams, MD, and Erin A. Gillaspie, MD, MPH
Published: Tuesday, Sep 25, 2018
Vanderbilt Cancer CenterWade T. Iams, MD
Wade T. Iams, MD
 
Instructor in Medicine
Department of Medicine
Division of Hematology/ Oncology,
Vanderbilt-Ingram Cancer Center Nashville, TN
Erin A. Gillaspie, MD, MPH
Erin A. Gillaspie, MD, MPH
 
Assistant Professor, Department
of Thoracic Surgery
Vanderbilt-Ingram Cancer Center Nashville, TN
Strategic Partnership

Current Standard of Care: Are Outcomes Satisfactory?

Neoadjuvant chemotherapy with or without radiation has become the preferred treatment in patients with resectable stage IIIA non–small cell lung cancer (NSCLC).1 However, results from studies have not shown a similar survival benefit for patients with early-stage (I or II) NSCLC who are candidates for upfront resection.2,3

This may be changing with the introduction of neoadjuvant immunotherapy, as described in the plenary presentation “Immunotherapy Combinations: The New Frontline in Lung Cancer” at the 2018 American Association for Cancer Research meeting and in a study by Forde et al published in the New England Journal of Medicine (NCT02259621).4

The multidisciplinary interest in improving the standard of care for patients with surgically resectable NSCLC stems from higher-than-desired local and systemic recurrence rates after resection1 and low 5-year survival.3 Improvement in outcomes for these patients is a major need.

Neoadjuvant Nivolumab Improves Major Pathologic Response Rate

In their recent publication, Forde et al demonstrated an impressive major pathologic response in 45% (9 of 20) of patients treated with 2 preoperative doses of nivolumab (Opdivo) with no delays in surgical resection.4 Major pathologic response is defined as <10% viable residual tumor at the time of resection. In the study, a major pathologic response was identified in 6 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, and 1 patient with pleomorphic carcinoma. By stage, these were 2 patients with stage I disease, 5 patients with stage II disease, and 2 patients with stage IIIA disease.

Interestingly, of the 9 patients with a major pathologic response, only 2 had a partial response on preoperative imaging, which calls into question the reliability of imaging as a marker for pathologic response to neoadjuvant nivolumab.4

Does Major Pathologic Response Really Matter?

Many studies use “major pathologic response” as a surrogate endpoint. But is this clinically meaningful?

Although this endpoint has not been fully evaluated in the context of neoadjuvant immunotherapy, it has been well defined for neoadjuvant chemotherapy administered to patients with resectable NSCLC.5 Results from neoadjuvant chemotherapy clinical trials with populations analogous to those in the pilot trial by Forde et al have shown that rates of major pathologic response correlate strongly with overall survival (OS).5 This finding is not unique to NSCLC, as rates of pathologic response correlate with OS in other malignancies, such as neoadjuvant chemotherapy in patients with breast cancer.6

Putting the pilot trial results in the context of resectable cancer, major pathologic response seems to be establishing itself as a good surrogate and predictor of survival in patients with NSCLC.

Chemotherapy Versus Immunotherapy

Most studies evaluating the efficacy of neoadjuvant chemotherapy in patients with resectable NSCLC reported a pathologic complete response rate of 0% to 20%,2,3,5,7,8 with the highest reported response rate in the literature being 27% (in 11 of 41 patients) after 3 doses of neoadjuvant bevacizumab.9

In the historical context of neoadjuvant chemotherapy, the major pathologic response rate of 45% achieved by Forde et al is impressive.


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: New Directions in Advanced Cutaneous Squamous Cell Carcinoma: Emerging Evidence of ImmunotherapyAug 13, 20191.5
Publication Bottom Border
Border Publication
x