In 2017, the American Society of Clinical Oncology and the non-profit organization Friends of Cancer Research noted in their joint statement that trial enrollment criteria should strive for inclusiveness to make trial populations more representative and to maximize generalizability of findings. Also, this would enable more patients to participate and accelerate accrual, resulting in expedited availability of new therapies.
Only limited therapeutic options are available for patients with relapsing small-cell lung cancer (SCLC). Topotecan is the only FDA-approved treatment for platinum-sensitive disease in the second-line setting. However, it induces merely modest clinical benefits, while at the same time giving rise to significant hematological toxicity.
MET exon 14 skipping mutations (METex14) have been reported in 3 % to 4 % of NSCLC patients. They confer poor prognosis and poor responses to standard therapies including immunotherapy. Moreover, patients with MET alterations are generally older, which implies that tolerable strategies are called for. Capmatinib has been developed as a highly selective, potent MET inhibitor with in vitro and in vivo activity against preclinical cancer models harboring MET activation.
What can we expect from circulating free DNA (cfDNA) as a biomarker in the setting of lung cancer diagnosis and treatment today?
KEYNOTE-001 was the first trial to demonstrate the activity of the PD-1 inhibitor pembrolizumab in patients with treatment-naïve or previously treated advanced NSCLC. Notably, in this multicohort phase IB study, pembrolizumab showed greater activity with increasing PD-L1 tumor proportion score (TPS). Between May 2012 and July 2014, 550 patients with advanced NSCLC had been enrolled across 4 non-randomized and 2 randomized cohorts.
Although treatment with EGFR TKIs is generally efficient in patients with EGFR-mutant lung cancer, resistance inevitably develops within 8 to 12 months of the initiation of therapy, leading to treatment failure. Therefore, there is an unmet need for options that extend the activity of EGFR-targeted therapies. Dual blockade of the VEGF and EGFR signaling pathways represents a potential approach in this respect.
Effective treatment options are called for in patients with resectable non-small-cell lung cancer (NSCLC), as more than half of those with stage I to III disease experience relapses [1]. Chen et al. demonstrated in their animal model that tumor PD-L1 upregulation is critical for the spread and survival of metastases [2]. Based on these considerations, several clinical trials are investigating the potential benefits of immunotherapies in the neoadjuvant setting.
Lung cancer is still a global public health problem and the first cause of cancer-related mortality everywhere in the world. Nowadays, this has particular implications for elderly patients considering the generally increasing life expectancy in conjunction with the rising cancer incidence with age. At the time of diagnosis, the median age of patients with lung cancer is 70 years in the USA and 65 to 70 years in Europe.
