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ECCO 2017 webcasts - Part 3
"Maximizing Treatment Outcomes in Patients with Advanced Metastatic Lung Cancer" by Giorgio V Scagliotti
Giorgio V Scagliotti
University of Turin
Giorgio Scagliotti reviews the treatment evidence from the past 10 years for advanced metastatic lung cancer. He builds a current treatment algorithm, and starts by presenting a case study of a 65-year old male, non-smoker diagnosed with adenocarcinoma (Stage IV), who shows a negative result to all molecular tests.
He presents clinical trial data that shows plateauing of response in a non-selective manner using different combination therapies. He discusses the evidence from various randomized clinical trials and meta-analyses on maintenance therapies, demonstrating that in the nonsquamous non-small cell lung cancer (NS-NSCLC) setting pemetrexed maintenance therapy until progression gives an additional benefit.
Although molecular approaches involving biomarker analyses have resulted in more targeted therapies, gaps remain, particularly in the subset with KRAS mutations, for which there are no targeted therapies.
In a second case study, a 55-year old male, non-smoker is diagnosed with adenocarcinoma (Stage IV). Molecular testing reveals an epidermal growth factor receptor (EGFR) exon 19 deletion, but no anaplastic lymphoma kinase (ALK) or ROS1 translocations. In this case, Dr Scagliotti recommends using appropriately targeted agents until progression. To illustrate this, he reviews a combined overall-survival analysis dataset that demonstrated a clear treatment benefit using afatinib versus chemotherapy in patients with an exon 19 mutation, but no such benefit with an exon 21 mutation.
In a recent clinical trial study, LUX-Lung 7, afatinib was compared to gefitinib in patients with Stage IIIB/IV lung adenocarcinoma and an EGFR mutation. There was no significant difference in progression-free survival or overall survival (OS), however the small enrolment number (n=319) means that these results should be interpreted with caution.
Squamous non-small cell lung cancer (SQ-NSCLC) arises from the proximal airways, can lead to more central cancers and more comorbidities and has a high mutational burden. The standard therapy is cisplatin/carboplatin for 4-6 courses and there is no role for maintenance therapy. Several studies have demonstrated statistically significant improvements in overall response rate (ORR) or OS as primary endpoints with several different regimens, but the clinical relevance of these findings is minimal.
Dr Scagliotti summarizes findings from a study comparing pembrolizumab to platinum-based chemotherapy as first-line therapy. Subjects with NSCLC and high programmed death 1 ligand (PD-L1) expression were included and results showed PFS of 10.3 vs 6.0 months for pembrolizumab vs platinum-based chemotherapy. Out of a screening number of 1934 patients, only 300 were randomized, so caution is advised in translating these results to the clinical setting.
There remain a number of questions around immune-oncology including: Is PD-L1 expression is relevant for selecting patients and at what level? What is the correct sequencing of immunotherapies and chemotherapies? What about immunotherapy-immunotherapy combinations, and what is the duration of treatment?