Lung Congress to Offer Thorough Review of Latest Research Findings

David R. Gandara, MD

The 15^th Annual International Lung Cancer Congress, which began today in Huntington Beach, California and will continue through Saturday, will offer an array of information presented by multidisciplinary experts—in a brand-new format.

“It’s set up to be a think tank, with 200 lung cancer experts plus participants [from the audience endeavoring] to digest what was presented earlier in the year at ASCO [the American Society of Clinical Oncology] and other conferences,” said Program Director David R. Gandara, MD, professor of Medicine in the Division of Hematology/Oncology, director of the Thoracic Oncology Program, and senior advisor to the director at the University of California Davis Comprehensive Cancer Center, in Sacramento.

Serving as a program director alongside Gandara is Roy S. Herbst, MD, PhD, Ensign Professor of Medicine (Medical Oncology), professor of Pharmacology, chief of Medical Oncology, and associate director for Translational Research at Yale Cancer Center in New Haven, Connecticut.

“We have leaders from all different specialties in lung cancer—pulmonary medicine, radiology, surgery, radiation oncology, medical oncology, molecular biology, pathology—on the faculty,” Gandara continued. “We will discuss management of cases where multiple modalities are required, such as surgery plus chemotherapy and radiation, and how to do molecular testing on patients. We’ll talk about that in panel discussions, and we’ll have a community-based multi-modality tumor board, during which we’ll talk about cases. Participants from the community can bring up cases in their practice and ask the expert panel how they would manage this sort of thing.”

International Experts

Lung Cancer Screening

Targeted Immunotherapy

In an interview with OncLive, Gandara discussed some other anticipated highlights of the conference.“Our faculty includes international experts, such as Giorgio Scagliotti, MD, PhD, of Italy, and James CH Yang, MD, PhD, from Taiwan, this year, because many of the lead studies at ASCO and other recent conferences were presented by these people,” Gandara said. “Dr. Yang announced for the first time, at ASCO, that patients with a certain EGFR mutation—the exon 19 deletion—who received afatinib had an overall survival improvement.¹ Seven prior studies looked at first-generation agents, and an overall survival improvement has never been seen, so we’ll be able to discuss that among our expert faculty and the participants to reach some conclusions about how we think about those data and how they might be taken into clinical practice. This will probably lead to increased use of afatinib in the first-line setting.”“Also exciting will be a presentation on lung cancer screening by James L. Mulshine, MD, [professor, associate provost for Research, and vice president of Rush University Medical Center in Chicago, Illinois],” Gandara said. “This has been an area of a lot of excitement and controversy over the last few months. The National Lung Screening Trial in the United States showed a 20% reduction in lung cancer death by screening with low-dose CT scan [compared to x-rays], yet [the Medicare Evidence Development & Coverage Advisory Committee] made a preliminary decision not to recommend reimbursement for screening. Dr. Mulshine is an expert in this area, and we have a number of other experts in this field who will attend and discuss this with him. That clearly will be a highlight of the meeting, which is usually focused [strictly] on lung cancer treatment.”“Another area of tremendous interest I’d call ‘targeted immunotherapy,’ particularly with drugs against the target CDL1,” Gandara said. “There are half a dozen drugs targeting this immunotherapeutic molecular target. We’ll talk—both in lectures and panel discussions—about data, how to measure the degree of activity, and whether there is too much hype about these agents, so we’ll be able to reach some consensus.

We’ll have Vassiliki Papadimitrakopoulou, MD [professor in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, in Houston] talk about why we must use different response measurements to determine how effective these drugs are. In immune therapy, T cells are invading the tumor initially, and with these treatments, the tumor can swell and look larger on a CT scan, so how does the physician know if the cancer is getting worse or if it’s an immune response and will get better with continued treatment? She’ll talk about this challenge.

Keynote Presentations

We’ll also have sessions that are designed to talk about the unique toxicities of this sort of immune blockade. Patients and doctors tend to think that other therapies can be toxic, even drugs like erlotinib, but that immune therapies are generally not, and that’s not true for these—there can be substantial toxicities, and we’ll discuss that.”“One of the most exciting of these will be the presentation of the 7^th Annual Addario lecture by Dr. Herbst,” Gandara said. “The Bonnie J. Addario Lung Cancer Foundation has a lung advocacy group, and each year they select someone they consider a leader in breakthrough research in the field to deliver a keynote address. Dr. Herbst will be speaking about the biology of the immune system in lung cancer. I expect that to be very well-received, and a great follow-up to last year’s keynote, in which Tony SK Mok, BMSc, MD, FRCPC, [of Hong Kong], talked about making war on cancer.”

Other keynote talks will include “Potential for ‘Curing’ Metastatic Non-Small Cell Lung Cancer,” presented by Paul Bunn, Jr., MD, and “TKI Combination Strategies,” presented by Dr. Yang.

“For Dr. Bunn, the concept is that, with targeted therapies like erlotinib in EGFR-mutated cancer or crizotinib in ALK-rearranged cancer, the response rate can be very high—70% or more—and the duration can be very long, but no patient has been cured, even with these breakthroughs,” Gandara said. “For the first time, Dr. Yang showed there was increased survival using a new drug, and in the Southwest Oncology Group we plan to combine that drug with another EGFR agent, cetuximab, for firstline treatment of EGFR-mutated cancers to see if that further boosts activity. We’re talking conceptually about how to transfer chronic disease, metastatic lung cancer, into curable disease.

Next-Generation Agents for Lung Cancer

In Dr. Yang’s talk, one issue is: How do you combine these therapies in a way where they are at least additive to each other, and in a way that has acceptable toxicity? Even with some of the combination immune therapies, the toxicity seems very high. So, should you give these drugs together, or sequentially? Are there ways to determine when to add a second agent based on a biomarker in the blood?”The congress agenda will include discussions of experimental drugs in various classes: FGFR inhibitors, drugs that target the ROS1 rearrangement, PI3K inhibitors, inhibitors of HSP90, drugs targeting the cMET proto-oncogene, agents targeting the RET fusion gene, and PARP inhibitors.

Cooperative Groups

“Drs. Papadimitrakopoulou and Herbst are the co-chairs of a new Lung Cancer Master Protocol, the Lung-MAP, or SWOG S1400.² It just launched last month, and it’s an example of an umbrella trial,” Gandara said. “Patients with squamous cell lung cancer undergo next-generation sequencing of over 200 genes in their cancer, and then are placed in arms of the Master Protocol, which matches a biomarker found in their cancer with a drug against that biomarker. It’s a one-of-a-kind study, a private-public partnership between the NCI [National Cancer Institute] and cooperative groups, with the foundation of the NIH [National Institutes of Health] and also the FDA. It’s the first time we’ll do this in a way where we can actually seek approval from the FDA for each biomarker and drug [if they meet their phase III endpoints during the trial]. That will be blended into our discussions at the conference—how you put new agents into the Master Protocol.”“An area unique to this meeting that will occur nowhere else is an entire session devoted to cooperative group trials throughout the world,” Gandara said. “In the United States, there’s been a reorganization and consolidation of cooperative groups. We’ll address new studies in all the groups and hear presentations from Europe and Asia about large, multi-institution trials being done there.”

References

1. Yang J C-H, Sequist LV, Schuler MH, et al. Overall survival in patients with advanced non-small cell lung cancer harboring common (Del19/L858R) epidermal growth factor receptor mutations: Pooled analysis of two large open-label phase III studies (LUX-Lung 3 and LUX-Lung 6) comparing afatinib with chemotherapy. J Clin Oncol. 2014;32:5s (suppl; abstr 8004^).
2. Friends of Cancer Research. Lung-MAP - The Lung Cancer Master Protocol. FOCR website. http://www.focr.org/lung-map. Accessed July 15, 2014.

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