My Top 5 Most Practice-Changing Presentations at WCLC

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The 19th World Conference on Lung Cancer took place in Toronto, Canada from September 23–26, 2018. It was a gathering of world-leading scientists and clinicians dedicated to advancing the treatments of lung cancer, and other thoracic malignancies such as mesothelioma, thymoma and thymic carcinoma. As expected, immunotherapy played the major role in presentations of all thoracic diseases. So what were the major and most interesting potentially practice-changing presentations?

The top 5 studies were presented at the presidential symposium. Three of these 5 trials were simultaneously published in the New England Journal of Medicine. The most anticipated, and first presentation was the update on overall survival of the PACIFIC phase III trial, which randomized patients with NSCLC stage IIIA/B to chemoradiation followed by durvalumab or placebo for one year. Impressively, OS at 1 year was 83% vs 75% and 2-year 66% vs 55% in durvalumab compared to placebo. Importantly, the benefit of durvalumab was in all patient subgroups. Similar results were observed with pembrolizumab in a phase II trial with the same concept. These results firmly establish this treatment paradigm in advanced loco-regional NSCLC. Future will look into concomitant combination of immunotherapy and chemoradiation followed by additional adjuvant immunotherapy. It will be important to learn about the loco-regional disease control with this treatment paradigm and whether addition of surgical resection in selected patients would provide additional survival benefit in advanced IIIA/B NSCLC.

The second practice-changing abstract compared the effectiveness of brigatinib versus crizotinib in patients with ALK inhibitor-naïve advanced ALK+ NSCLC; this was the first report of phase III ALTA-1L trial. This trial of 275 randomized patients demonstrated both statistically and clinically significant improvement in progression-free survival with brigatinib compared to crizotinib in this patient population.

Two additional high-value studies presented at the presidential symposium included NELSON randomized-controlled population-based trial of lung cancer CT screening, and IMpower 133, the study of atezolizumab combined with carboplatin and etoposide in extensive-stage small cell lung cancer. NELSON lung cancer screening trial was conducted in the Netherlands and demonstrated an impressive 94% compliance rate. Importantly, CT screening decreased lung cancer mortality in men with HR 0.75 (CI 0.59–0.95) and women with HR 0.39 (0.18–0.78) at 8 years; results being more robust than the U.S. National Lung Screening Trial in terms of the overall survival benefit of CT lung cancer screening.

IMpower 133 regimen of atezolizumab combined with carboplatin and etoposide will likely become the new first line standard treatment for extensive stage small cell lung cancer. The addition of atezolizumab to the standard chemotherapy regimen demonstrated significantly better overall survival in the treatment vs placebo arm, albeit by only 2 months (12.3 vs 10.3 months, atezolizumab vs placebo respectively).

Last study presented at the presidential symposium was a phase III LUME-Meso trial, which compared nintedanib plus pemetrexed and cisplatin with standard pem-cis regimen. Randomized phase II portion of this trial previously demonstrated encouraging improvement in PFS with nintedanib, which is a tyrosine kinase triple angiogenic inhibitor. Unfortunately, the primary endpoint (PFS) of the phase III portion was not met and results from the phase II portion of the trial were not confirmed, leaving mesothelioma patients with currently established first line regimen of cisplatin and pemetrexed in unresectable or metastatic setting.

Advancements in lung cancer therapy and other thoracic malignancies are evolving more rapidly than ever before, thanks to immunotherapy and improved understanding of cancer biology on immunologic and genomic and all “other-omic” level. There are presently hundreds of additional new studies, which will further define the future treatments of these deadly diseases. The 20th World Lung Cancer Conference in Barcelona, Spain, is now less than a year away, and updates on many important trials are eagerly anticipated.

By Boris Sepesi, MD, FACS is an assistant professor and thoracic surgeon at the University of Texas MD Anderson Cancer Center specializing in the treatment thoracic malignancies, specifically lung cancer, esophageal cancer and mesothelioma. He also serves as a co-PI on clinical trials utilizing neoadjuvant immunotherapy in surgically resectable lung cancer and mesothelioma. He reports no conflicts of interest.

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