Introduction: Immunotherapy for Non–Small Cell Lung Cancer: Advances and Challenges

Roy S. Herbst, MD, PhD

Roy S. Herbst, MD, PhD

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related mortality in the United States, with an estimated 224,390 new cases and 158,080 deaths from the disease in 2016.1 Despite improving survival rates in recent decades, only about 18% of patients are still alive 5 years after diagnosis, underscoring a major unmet need for better therapies.

Lung and other cancers often escape destruction by the immune system by exploiting checkpoint pathways, which serve as a natural brake on the immune response, such as the programmed cell death protein 1 (PD-1) pathway.2 Agents that inhibit these immune checkpoints can overcome this form of escape and restore antitumor responses, often with dramatic effect.

Many of the recent advances in immunotherapy were reported and discussed at the 17th World Conference on Lung Cancer, the biennial meeting of the International Association for the Study of Lung Cancer (IASLC). The conference was held in Vienna, from December 4 to 7, 2016. It drew more than 6,500 attendees, including many leaders in the field, from 90 countries and from diverse institutional settings and specialties. Reports on several of the studies presented at the conference are included in this supplement to The ASCO Post

Improving the Standard of Care

Taken together, the findings reported at IASLC gave good reason for excitement in the field. They confirmed unprecedented and superior efficacy of immune checkpoint inhibitors over the previous standards of care, with good safety and tolerability, and better quality of life. They revealed the emergence of a subset of patients with advanced disease seeing long-term survival. They established benefit across diverse subgroups of patients. And following on experience in the melanoma field, data provided compelling evidence that a combination of two immunotherapies may outperform monotherapy.

Conference presenters and attendees also grappled with various challenges and unanswered questions. What are the implications of the differential performance of the various assays used to assess tumor biomarker status? What is the optimal threshold for defining positivity? And how can we more reliably identify patients who will—and will not—ultimately benefit from these agents, and which will be key to optimizing their cost-effectiveness in real-world practice? Immune-mediated toxicities, which are relatively uncommon but can be severe and treatment-limiting, were also discussed.

These issues and others are being actively investigated in numerous ongoing clinical trials, a number of which are discussed herein. Results of several potentially practice-changing trials are expected in the next few years, and these studies hold great potential for further improving outcomes in this disease. ■

—Roy S. Herbst, MD, PhD
Guest Editor


1. Siegel RL, Miller KD, Jemal A: Cancer statistics, 2016. CA Cancer J Clin 66:7-30, 2016.

2. Melosky B, Chu Q, Juergens R, et al: Pointed progress in second-line advanced non-small-cell lung cancer: The rapidly evolving field of checkpoint inhibition. J Clin Oncol 34:1676-1688, 2016.