Posted: February 2017
By Lori Alexander, MTPW, ELS, MWC
With more than 2,500 presentations at the IASLC World Conference on Lung Cancer (WCLC) 2016, in Vienna, Austria, it is impossible to report on all new developments in the prevention, diagnosis, and treatment of lung cancer. However, some themes did emerge, most notably tobacco control and smoking cessation, improvements in diagnosis and prognosis, and advances in targeted therapy and immunotherapy.
Tobacco Control and Smoking Cessation
Tobacco control remains a crucial topic in the lung cancer community, and the issue was at the forefront of WCLC 2016. Perhaps the most inspiring of the presentations on tobacco control belonged to President of Uruguay Tabaré Vázquez, MD, who spoke at Monday’s Plenary Session.Before the session, Heinz Fischer, former president of Austria, welcomed Dr.Vazquez as well as WCLC delegates. Dr. Vázquez is widely recognized—and revered—for his stance against the tobacco industry. Uruguay won a landmark decision this year when an international arbitration tribunal ruled against the claim by Philip Morris International that two of Uruguay’s tobacco-control measures violated the terms of a Bilateral Treaty between Uruguay and Switzerland. The tribunal dismissed all of Philip Morris International’s claims and awarded Uruguay $7 million for its legal costs.
“Uruguay just exerted its sovereign right to protect its people’s life and health,” said Dr. Vázquez.
Vera Luiza da Costa e Silva, MD, PhD, Secretariat for the World Health Organization’s Framework Convention on Tobacco Control, also spoke at the Plenary Session. She addressed the tobacco industry’s condemnation of tobacco control efforts, in that the multibillion- dollar transnational industry warns against a “nanny state” and supports “an adult’s right to choose,” while at the same time aggressively and deceptively advertising its product.
“We cannot work with or permit the tobacco industry to play any part in public health measures,” said Dr. da Costa e Silva. “Despite all its [the tobacco industry’s] protestations,” she added, “it is not fit to offer one crumb of advice against those of us who fight against the epidemic it has so effectively and cruelly engineered around the world.”
Several other WCLC sessions addressed tobacco control specific to various countries and regions, and many European countries continue to struggle with implementing policies.
“Up to now, strategies of tobacco control, which were successful in Australia, North America, and Western Europe, have been introduced only in a few Central European countries,” said Manfred Neuberger, MD, Vienna, Austria, who co-chaired the Meet the Expert Session “Strategies to Improve Tobacco Control in Central European Countries.”
Dr. Neuberger said that, according to a ranking system in which many factors were considered (e.g., tobacco price increases, smoking restrictions, and advertising bans), Austria, Germany, Cyprus, the Czech Republic, Greece, and Lithuania are lagging in their tobaccocontrol efforts and need to fight more strongly against the tobacco industry’s influence.
Smoking cessation was also discussed extensively in several sessions, including the nursing session “Prevention,” in which speakers explored the role of nurses in smoking cessation (see page11). In addition, speakers in sessions on lung cancer screening emphasized the importance of providing smoking-cessation services in the context of lung cancer screening programs. Integrating smoking cessation into these programs has been termed a “teachable moment” because of the associated high success rates. Of note, a recent study showed that smoking cessation significantly reduced overall mortality among smokers enrolled in lung cancer screening programs. The beneficial effect appeared to be threefold to fivefold greater than that achieved by earlier detection in the National Lung Screening Trial.1 In addition, the integration of smoking-cessation services with lung cancer screening yields a significant cost benefit, reducing the overall expense of providing CT-based screening.
Improved Diagnosis and Prognosis
WCLC sessions provided an opportunity to highlight new publications on molecular testing and staging: most notably updates of the “Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors,” a joint guideline developed by the College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) in 2013, and the 2016 edition of the IASLC Staging Manual in Thoracic Oncology.
The update to the molecular testing guideline was prompted by several factors, including newly discovered biomarkers with existing or potential targeted therapies (ROS1, MET, ERBB2, BRAF, RET, KRAS, and PIK3CA) and new markers of resistance (e.g., T790M), as well as advances in biotechnology— immunohistochemistry (IHC), nextgeneration sequencing, circulating cancer cells, and cell-free DNA (cfDNA)—and reconsideration of testing in squamous and small cell cancers. The revisions to the guideline are based on evidence from an unbiased review of published literature since 2013 and include recommendations from an expert panel of renowned worldwide leaders in the field.
The speakers at the Special Session, all members of the Expert Panel, provided a summary of the updated guidelines, noting that the 2013 recommendations are largely unchanged. Unfortunately, no new targets for squamous or small cell cancer have been identified, so testing remains limited to patients with advanced-stage lung cancers with an adenocarcinoma component. In the setting of acquired resistance, testing for the EGFR T790M mutation is recommended, as it occurs in approximately 50% of patients with disease progression on an EGFR inhibitor. In addition, T790Mspecific therapy is available (osimertinib). With regard to testing at the time of initial diagnosis, the new guidelines recommend adding ROS1 testing for all patients and adding testing for BRAF, ERBB2, MET, and RET if a larger panel is being obtained. PD-1/PD-L1 testing is important, but the Expert Panel determined that a separate guideline is needed for this testing. With regard to how to test, IHC is acceptable for ALK and ROS1 testing but not for EGFR testing; and nextgeneration panels are preferred over multiple single assays. Despite the evolving clinical utility of liquid biopsies and their potential advantages, published data are lacking. The new guidelines are scheduled for publication in early 2017 in the Journal of Thoracic Oncology, the Journal of Molecular Diagnosis, and Archives of Pathology & Laboratory Medicine.
The newly revised staging classification for lung cancer was the focus of several sessions. Ramón Rami-Porta, MD, PhD, Barcelona, Spain, Executive Editor of the IASLC Staging Manual in Thoracic Oncology, noted updates in the classification since the proposed revisions were presented at WCLC 2015 in Denver, primarily within the tumor (T) classification, with few changes to the node (N), and no changes to the metastasis (M) categories. Dr. Rami-Porta reviewed the new changes, focusing on how the updates will likely influence daily clinical practice. The new classification system has a greater focus on tumor size, and tumor size is now a descriptor in all T categories. Additionally, adenocarcinoma in situ (Tis [AIS]), squamous cell carcinoma in situ [SCIS], and minimally invasive adenocarcinoma (T1mi) each has its own coding in the TNM classification. These small tumors behave differently from larger ones and deserve further study with regard to growth rate, tumor density, intensity of uptake in positron emission tomography, optimal type of resection, alternative nonsurgical therapies, molecular characterization, and genetic signatures. Dr. Rami-Porta also discussed determination of tumor size for part-solid tumors. For this presentation, it is the size of the solid component of the tumor that determines prognosis. Measuring the entire size of the tumor would be misleading in classification and prognosis.
Advances in Targeted Therapy and Immunotherapy
Targeted therapy and immunotherapy were the focus of several of the highest-ranked abstracts submitted to WCLC 2016. Three phase III trials on targeted therapy—AURA3, BRAIN, and ASCEND-4—presented at the Presidential Symposium are changing practice for lung cancer specialists.
AURA3, the first randomized phase III trial of a third-generation EGFR inhibitor, showed that osimertinib was associated with a significantly longer progression-free survival (the primary endpoint) compared with standard-ofcare chemotherapy for patients with acquired T790M resistance (median, 10.1 vs 4.4 months; p<.001) with fewer grade 3 or higher adverse events. The study was published online in the New England Journal of Medicine simultaneously with the presentation.
BRAIN is the first phase III trial to compare an EGFR tyrosine kinase inhibitor with whole brain irradiation with or without chemotherapy (WBI ± chemo) in patients with NSCLC and brain metastases harboring EGFR mutations. Although EGFR tyrosine kinase inhibitors have demonstrated efficacy in EGFR-positive NSCLC, use of these inhibitors, in lieu of brain radiation, for brain metastases has been controversial. The inhibitor, icotinib, resulted in a significantly longer median intracranial progression-free survival (the primary endpoint) than WBI ± chemo (median, 10.0 vs 4.8 months; p=.014). Icotinib was also associated with longer progression-free survival (6.8 vs 3.4 months, p<.001) and a higher intracranial objective response rate (67.1% vs 40.9%, p<.001). However, overall survival was not significantly different between the treatment arms.
The ASCEND-4 trial was designed to evaluate the second-generation ALK inhibitor certinib, which is approved in Europe and the United States as second- line therapy following failure of, or intolerability to, crizotinib in patients with ALK-positive NSCLC. Based on an interim analysis of available data, the trial met its primary endpoint, with ceritinib resulting in a significantly longer median progression-free survival compared with standard of care (16.6 vs 8.1 months; p<.001) in treatment-naive ALK (+) NSCLC. Benefit was seen across all prespecified subgroups, including patients with or without brain metastases. There was a trend toward longer median overall survival in the certinib arm (not evaluable vs 26.2 months; p=.056), even though 72.4% of patients in the standardof- care arm subsequently received an ALK inhibitor following disease progression. The intracranial objective response rate was higher in the certinib arm (72.7% vs 27.3%).
The four highest-ranked abstracts on immunotherapy were presented in Wednesday’s Plenary Session (see coverage on page 1), and the use and study of immunotherapeutic agents continues to burgeon.
“As of a month ago, immunotherapy surpassed chemotherapy as first-line treatment for advanced non-small cell lung cancer in selected patients,” said Roy Herbst, MD, PhD, Yale School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, US. “So we have a totally new paradigm for treatment.”
1. Pastorino U, Boffi R, Marchianò A, et al. Stopping smoking reduces mortality in low-dose computed tomography screening participants. J Thorac Oncol. 2016; 11:693–699.