Debating the Merits of New Therapeutic Stars in NSCLC

Peter J. Sciavolino, PhD
Published: Thursday, Oct 29, 2015
Suresh S. Ramalingam, MD

Suresh S. Ramalingam, MD

Immunotherapies (immune checkpoint inhibitors) and targeted therapies (tyrosine kinase inhibitors [TKIs] that target specific mutations in one or more oncogenic drivers) represent two of the most researched types of therapy under investigation for the treatment of non– small cell lung cancer (NSCLC).

But which of these two types of therapy—both of which certainly offer bold new opportunities for disease control over cytotoxic therapies—do oncologists think has been, overall, the greater contributor to NSCLC treatment?

This was the topic of a session at the Debates and Didactics in Hematology and Oncology Conference, held in Sea Island, Georgia, July 22-26. OncologyLive caught up with the two presenters on the topic to weigh in on this timely debate.

On the Immunotherapy Side

Presenting the argument for immunotherapy was Suresh S. Ramalingam, MD, who is nationally recognized for his research in developing individualized therapies for patients with small cell and NSCLC. Ramalingam serves as co-leader for the Discovery & Developmental Therapeutics Program and director of the Medical Oncology and Lung Cancer Programs at Winship Cancer Institute, and professor of hematology and medical oncology at Emory University School of Medicine.

In his presentation, Ramalingam acknowledged the robust response rates seen with targeted therapies in patients with a driver mutation, but noted that resistance inevitably develops and leaves limited options for patients with acquired resistance. With that backdrop, he then described the durable responses seen in up to 25% of patients with immunotherapy, and the marked superiority of immunotherapy to chemotherapy in the salvage setting, as seen in the CheckMate and other studies.

He also emphasized the long-term survival that has been observed with combination therapies in other cancers, such as melanoma, and that targeted therapies (with or without combination) have thus far not resulted in cure for patients with NSCLC.

On the Targeted Therapies Side

Presenting the argument for targeted therapies was Fadlo R. Khuri, MD, a world-renowned lung cancer and head and neck cancer expert. Khuri serves as deputy director of Winship Cancer Institute and editor-in-chief of the journal Cancer. He is also professor and chairman of the Department of Hematology and Medical Oncology, and executive associate dean of research at Emory University School of Medicine.

During his presentation, Khuri noted that targeted therapies represent an opportunity to hone in on drivers of so-called oncogene-addicted cancers, and pointed to the high response rates and durable benefits associated with these therapies. He also emphasized the reliability and availability of biomarkers and genomic testing with targeted agents, and medicine’s growing understanding of potential resistance mechanisms (eg, T790M in acquired resistance to EGFR TKIs). He also believes that targeted therapies offer a better cost/ benefit ratio and fewer toxicities than immunotherapies, particularly compared with combined cytotoxic T-lymphocyte-associated protein 4 (CTLA–4)/ programmed cell death–1 (PD-1) blockade.

The Presenters Weigh In

Q: Which, in your opinion, has made the greater contribution to NSCLC treatment, targeted therapies or immunotherapy?

Ramalingam: Targeted therapies against driver mutations in advanced NSCLC patients have resulted in robust response rates and improvements in survival. However, resistance is inevitable, and the fact remains that targeted therapies have not helped improve cure rates in lung cancer. Immunotherapy provides the hope that longterm survival is achievable in a subset of patients. We hope that cures can be achieved with novel treatment approaches that include immunotherapy.

Khuri: Targeted therapies have contributed more to date, but immunotherapy stands to [make] the bigger, longer-term contribution, as it presents the possibility of long-term cure for a fraction of patients with metastatic disease. However, to date, targeted therapies have made a bigger impact, because, for the fraction of patients with lung cancer who have driver mutations (generally, nonsmokers), durable response and prolongation of survival [have been observed with] therapies targeted to EGFR, ALK, RAF, ROS, RET, and HER2.

Q: What are some of the key data from your presentation that you feel support this conclusion?

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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