JTO Clinical and Research Reports (Oct 2021)

Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC

  • Jay M. Lee, MD,
  • Anthony W. Kim, MD,
  • Tomasz Marjanski, MD, PhD,
  • Pierre-Emmanuel Falcoz, MD, PhD,
  • Masahiro Tsuboi, MD, PhD,
  • Yi-Long Wu, MD,
  • Shawn W. Sun, PharmD,
  • Barbara J. Gitlitz, MD

Journal volume & issue
Vol. 2, no. 10
p. 100221

Abstract

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Neoadjuvant immunotherapy may improve outcomes in patients with resectable NSCLC and is being evaluated in phase 2 and 3 studies. Nevertheless, preoperative treatment postpones resection; the potential for increased surgical complexity and greater intra- and postoperative morbidity and mortality is an additional consideration. In studies primarily designed to evaluate efficacy, the impact of neoadjuvant immunotherapy on surgery is based on parameters that are poorly defined and reported differently between studies. Defining and reporting common end points among trials would improve understanding and facilitate cross-comparison of different immunotherapy regimens and may facilitate wider adoption of induction therapies by surgeons and oncologists. We propose several surgical end points and related metrics for neoadjuvant immunotherapy in resectable NSCLC. These include the periods from screening to treatment initiation and from last neoadjuvant dose to surgery; reporting of the allowable window for surgery to preclude masking delays caused by induction treatment-related toxicity; complete resection (R0) rate; preoperative downstaging; a standardized list of immune-related adverse events and associated delay to surgery; preoperative attrition; postoperative attrition before adjuvant therapy; and postoperative 30- and 90-day mortality and morbidity rates. Intraoperative end points (blood loss, duration, and type of surgery) and our proposed system of grading complexity based on lymphadenopathy and fibrosis would allow quantitation of technical difficulty and quality of oncologic resection. In conclusion, the standardization, reporting, and prospective inclusion of these end points in study protocols would provide a comparative overview of the impact of different neoadjuvant immunotherapy regimens on surgery and ultimately clinical oncologic outcomes in resectable NSCLC.

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