In the United States and Canada, Labor Day, which celebrates the contributions of workers, falls on the first Monday in September and marks the unofficial end of summer. Fittingly, on the 6th of September, more than 4000 lung cancer physicians, researchers, advocates, and patients gathered in Denver, Colorado, to attend the 16th World Conference on Lung Cancer (WCLC). From now on a yearly event, the WCLC is planned and supported by the 40-year-old International Association for the Study of Lung Cancer and has become the main scientific and educational venue for those with an interest in thoracic malignancies.
Here is a review and summary of the four top-rated abstracts presented at the presidential symposium, with a discussion of how they fit into our current clinical practice and research efforts.
Cetuximab Plus Standard Treatment
The first study presented in the session was SWOG S0819, a randomized, phase 3 trial evaluating the addition of cetuximab, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), to standard treatment with carboplatin and paclitaxel (with or without bevacizumab) for patients with advanced non-small cell lung cancer (NSCLC). The co-primary endpoints were progression-free survival (PFS) in EGFR fluorescence in situ hybridization (FISH)-positive patients and overall survival (OS) in the entire study population. Secondary endpoints included OS and PFS by bevacizumab appropriateness and safety and toxicity in each arm. There was also an exploratory outcome assessing OS in patients with squamous cell histology.
Of 1333 patients enrolled, 554 were appropriate for treatment with bevacizumab, as they did not have squamous histology equal to or more than 50% of the tumor, hemoptysis of at least half a teaspoon, cavitary lesions, bleeding disorders, or other contraindications to the vascular endothelial growth factor (VEGF) inhibitor. A total of 656 patients were randomly allocated to receive cetuximab and 657 to the control arm. Both groups were balanced for baseline characteristics such as age, sex, smoking, performance status, and histology.
There were no statistically significant differences in OS and PFS for the entire population and for EGFR FISH-positive patients. Cetuximab improved OS for patients who were EGFR FISH-positive and who either had squamous histology or who were not appropriate candidates for bevacizumab. The 234 patients for whom bevacizumab was not appropriate and who were EGFR FISH-positive had a median OS of 11.2 months when treated with cetuximab and 8.7 months when they did not receive the anti-EGFR agent (hazard ratio [HR]=0.75; 95% confidence interval [CI], 0.57-0.998; P=.048]. For the 111 patients with squamous histology and EGFR FISH-positive disease, median OS was 11.8 months with cetuximab and 6.4 months without it [HR=0.56, 95% CI, 0.37-0.84, P=.006].
The authors concluded that these data suggest a role for EGFR FISH testing and treatment with anti-EGFR monoclonal antibodies, especially for patients who test positive, have squamous histology, or are otherwise not candidates to receive bevacizumab.
The use of EGFR FISH in S0819 was based on the Colorado Scoring Criteria previously described by Varella-Garcia and Hirsch. Patients are considered positive if their tumors have 40% or more cells displaying at least four copies of the EGFR signal, if there's a two or greater ratio of EGFR to CEP7 over all scored nuclei, or if 10% or more of cells display 15 or more EGFR copies or four or more gene cluster spots. Initial suggestion of the predictive value of EGFR FISH came from the SWOG 0342 study, which randomly assigned patients to receive chemotherapy and cetuximab in a concurrent or sequential schedule. Moreover, in the SQUIRE trial, which compared the addition of necitumumab to gemcitabine and cisplatin in the treatment of patients with advanced squamous lung cancer, EGFR FISH testing was also predictive of clinical benefit. For the 208 patients with EGFR FISH-positive disease, OS improved from 9.2 to 12.6 months with the addition of the monoclonal antibody (HR=0.70; 95% CI, 0.52-0.96; P value for interaction=.066).
In summary, when taken together, the data presented in Denver and the available literature suggest that selected patients with advanced NSCLC may derive benefit from the addition of monoclonal antibodies targeting EGFR, but further study is needed for confirmation.
Medscape Oncology © 2015 WebMD, LLC
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Cite this: 16th World Conference on Lung Cancer (WCLC) Presidential Symposium: Summary and Clinical Implications - Medscape - Oct 12, 2015.