Precision oncology is now the evidence-based standard of care for the management of many advanced non-small cell lung cancers (NSCLCs). Expert consensus has defined minimum requirements for routine testing and identification of epidermal growth factor (EGFR) mutations (15% of tumors harbor EGFR exon 19 deletions or exon 21 L858R substitutions) and anaplastic lymphoma kinase (ALK) rearrangements (5% of tumors) in advanced lung adenocarcinomas (ACs). Application of palliative targeted therapies with oral tyrosine kinase inhibitors (TKIs) in advanced/metastatic lung ACs harboring abnormalities in EGFR (gefitinib, erlotinib, afatinib) and ALK/ROS1/MET (crizotinib) has consistently led to more favorable outcomes compared with traditional cytotoxic agents. In addition, mutations leading to resistance to first-line EGFR and ALK TKIs can now be successfully inhibited by soon to be approved third-generation EGFR TKIs (osimertinib, rociletinib) and second-generation ALK TKIs (ceritinib, alectinib). Notably, increasing feasibility, accessibility, and application of molecular profiling technologies has permitted dynamic growth in the identification of actionable driver oncogenes. Emerging genomic aberrations for which TKIs have shown impressive results in clinical trials and expansion of drug labels for approved agents are awaited include ROS1 rearrangements (1-2% of tumors, drug: crizotinib) and BRAF-V600E mutations (1-3% of tumors, drugs: vemurafenib, dafrafenib + trametinib). Evolving genomic events in which TKI responses have been reported in smaller series include MET exon 14 skipping mutations (2-4% of tumors, drug: crizotinib); high-level MET amplification (1-2% of tumors, drug: crizotinib); RET rearrangements (1% of tumors, drug: cabozantinib); and ERBB2 mutations (2-3% of tumors, drug: afatinib), among others. Unfortunately, the most common genomic event in NSCLC, KRAS mutations (25-30% of tumors), is not targetable with approved or in development small molecule inhibitors. Here, we review currently approved, emerging, and evolving systemic precision therapies matched with their driver oncogenes for the management of advanced NSCLC.
Introduction Targeted somatic genomic analysis (EGFR, ALK and ROS1) and PD-L1 tumor proportion score (TPS) by immunohistochemistry (IHC) are used for selection of 1st-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported. Methods We retrospectively probed the first 71 lung adenocarcinoma-patient pairs from our institution analyzed for PD-L1 IHC using the clone 22C3 pharmDx kit and evaluated co-occurrence of genomic aberrations along with clinical-pathologic characteristics. Results Surgical resection specimens, small biopsies (transbronchial or core needle), and cytology cell blocks (needle aspirates or pleural fluid) were tested. PD-L1 TPSs of ≥50% were seen in 29.6% of tumors. Of 19 tumors with EGFR-mutations, ALK-FISH positivity, or ROS1-FISH positivity, 18 had PD-L1 TPS <50% versus only 1 tumor with PD-L1 TPS ≥50% (p=0.0073). PD-L1 TPS ≥50% tumors were significantly associated with smoking status compared to PD-L1 TPS <50% tumors (p=0.0111); but not with patient gender, ethnicity, tumor stage, biopsy site, or biopsy type/preparation. Conclusions PD-L1 IHC can be obtained in routine clinical lung cancer specimens. TPS of ≥50% seldom overlaps with presence of driver oncogenes with approved targeted therapies. Three biomarker-specified groups of advanced lung adenocarcinomas can now be defined, each paired with a specific palliative first line systemic therapy of proven clinical benefit: 1) EGFR/ALK/ROS1-affected with matched tyrosine kinase inhibitor (~20% of cases), 2) PD-L1-enriched (TPS ≥50%) with anti-PD-1 pembrolizumab (~30% of cases), or 3) biomarker negative (i.e. EGFR/ALK/ROS1/PD-L1 negative) with platinum doublet chemotherapy with/without bevacizumab (~50% of cases).
Objectives-Financial toxicity is increasingly recognized as an adverse outcome of cancer treatment. Our objective was to measure financial toxicity among gynecologic oncology patients and its association with demographic and disease-related characteristics; self-reported overall health; and cost-coping strategies. Methods-Follow-up patients at a gynecologic oncology practice completed a survey including the Comprehensive Score for Financial Toxicity (COST) tool and a self-reported overall health assessment, the EQ-VAS. We abstracted disease and treatment characteristics from medical records. We dichotomized COST scores into low and high financial toxicity and assessed the correlation (r) between COST scores and self-reported health. We calculated risk ratios (RR) and 95% confidence intervals (CI) for the associations of demographic and disease-related characteristics with high financial toxicity, as well as the associations between high financial toxicity and cost-coping strategies.
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