Relevance of multi?disciplinary team approach in diagnosis and management of Stage III NSCLC

Lung cancer is reported as the leading cause of cancer?related mortality worldwide. Non?small cell lung cancer (NSCLC) constitutes 80%�% of all lung cancers. Diagnosis of NSCLC is a complex multistep process. The prognosis of NSCLC is poor as most of the patients are presented at the metastatic stage. The management of these patients needs the expertise of different specialists. A multidisciplinary team (MDT) comprising specialists from different disciplines has a substantial role in improving outcomes in these patients. This is feasible through extensive discussions, accurate evaluation of patients, reviewing medical records, implementing ideal treatment strategies, and merging local treatments with systemic treatment concepts. Therefore, the MDT approach for stage III NSCLC management can enable early treatment initiation, optimal treatment modalities, and reduce healthcare expenditure. Studies have shown that MDT can provide multimodality care facilitating the diagnosis and treatment of stage III NSCLC, resulting in survival benefit of these patients. Thus, it is imperative to collate scientific evidence to get an insight into the MDT approach in advanced NSCLC treatment. This review aims to summarize the impact of MDT on treatment rates, survival outcome, treatment guideline adherence, and quality of life (QoL) of stage III NSCLC patients.

CONCORDANCE: A real?world evidence study to evaluate the concordance of detecting epidermal growth factor receptor (EGFR) mutation by circulating tumor DNA* versus tissue biopsy in patients with metastatic non?small cell lung cancer

Background: Molecular tissue testing in non?small cell lung cancer (NSCLC) is done for the assessment of epidermal growth factor receptor (EGFR) mutation. EGFR mutation status is the basis for deciding the targeted treatment option for patients with metastatic NSCLC. The nonavailability of tissue samples and contraindications for biopsy pose a significant challenge. Hence circulating tumor DNA (ctDNA) by liquid biopsy can be a viable alternative for NSCLC patients. Methods: This study was conducted at 15 sites across India. EGFR mutation testing from plasma was done as part of the study at the central laboratory by the next?generation sequencing (NGS) method and EGFR mutation test results from tissue samples (done as part of routine practice) were recorded for all the patients. Results: Out of the total patients enrolled (N = 245) the majority (64.5% n = 158) were men. The median age of patients was 58.0 (range: 26�) years. The concordance between plasma and tissue testing was found to be 82.9% (95% confidence interval [CI]: 77.55 87.45). The sensitivity and specificity of NGS were 68.4% (95% CI: 56.92 78.37) and 90.1% [95% CI: 84.36 94.21) respectively. Plasma testing detected 1.2% (n = 3) and tissue sample testing detected 2.4% (n = 6) positive status of exon 20 T790M EGFR mutation. Out of the total number of patients enrolled 25 were tissue positive and plasma negative while 16 were plasma positive and tissue negative. Conclusions: This real?world study in Indian patients suggests that plasma testing for EGFR mutation analysis is a viable diagnostic option in newly diagnosed advanced/metastatic NSCLC patients. The noninvasive plasma procedure in patients without available/evaluable tumor sample may enable more patients to receive appropriate targeted therapies by providing clinicians with valuable insights into the patient抯 tumor mutation status. ClinicalTrials.gov Identifier: NCT03562819

Safety of osimertinib in adult patients with metastatic epidermal growth factor receptor T790M mutation?positive non?small cell lung cancer: Results from a Phase IV study in India

Background: A Phase IV, single?arm study was conducted to assess the safety of osimertinib in Indian patients with epidermal growth factor receptor (EGFR) T790M mutation?positive stage IV non?small cell lung cancer (NSCLC). Methods: Enrolled patients received 80 mg osimertinib for six cycles or until disease progression or unacceptable toxicity or withdrawal. Primary safety variables included treatment?emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) leading to discontinuation/interruption/change (D/I/C) of drug dose, and AEs of special interest (AESIs). AEs were summarized by the percentage of patients experiencing at least one occurrence of each event. Results: Of the 60 enrolled patients (median age 58 [range: 34�] years; 51.7% women) at eight sites, nine patients were discontinued prematurely due to disease progression (n = 7) and death (n = 2); median (range) duration of treatment was 126 (1�4) days. Median age of patients was 58 (34�) years; 51.7% (n = 31) were women; 86.7% (n = 52) were nonsmokers; and most of them (98.3%) had adenocarcinoma. About 75% (n = 45) of patients experienced any of the TEAEs, with the most frequent being fatigue and creatine phosphokinase (CPK) increase (n = 6, 10% each). TEAEs in 11 (18.3%) patients were judged as study treatment related, with CPK increase being the most common (n = 4, 6.7%). TEAEs led to D/I/C of drug dose in eight (13.3%) patients, with one being study treatment related. Nine (15%) patients had AESIs of dyspnea (n = 6), chest pain (n = 2), and cardiorespiratory arrest (n = 1); two of them had a fatal outcome. One AESI (mild dyspnea) was considered study drug related. TEAEs of grade ?3 were reported in seven (11.7%) patients, including dyspnea in two (3.3%), followed by diarrhea, mucosal inflammation, cardiorespiratory arrest, and others (n = 1,1.7% each). None of the SAEs and fatal events were considered as study treatment related. Seven (11.7%) patients had abnormal electrocardiogram (ECG; not clinically significant) at the end of the study. Conclusion: Our study confirms the favorable safety profile of osimertinib without any new safety concerns in Indian patients with EGFR T790M mutation?positive stage IV NSCLC. ClinicalTrials.gov Identifier: NCT03853551 CTRI registration no. CTRI/2018/10/015941

Biomarker testing for advanced lung cancer by next-generation sequencing; a valid method to achieve a comprehensive glimpse at mutational landscape

Background: Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients. Methods: Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform. Results: One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015). Conclusions: This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer

Synergistic Occurrence of EGFR, ALK, and KRAS Gene Mutations in a Patient with Non-small Cell Lung Cancer (Adenocarcinoma)

Lung cancer is a commonly diagnosed malignancy. Adenocarcinoma, a subgroup of non-small cell lung cancer, is the commonest form and presents in an advanced stage of the disease, leaving a limited treatment option. Response to the standard chemotherapy regimens is overall poor. We present a case of synergistic occurrence of triple gene mutations in a patient with well-diff erentiated adenocarcinoma lung treated at a tertiary cancer care center in North India.

Case Report of Non-small Cell Lung Cancer Patient with EGFR T790M Mutation Treated with Th ird Generation Inhibitor

Lung cancer treatment based on the molecular classifi cation of the tumor has paved the way for multiple lines of targeted treatment, even though the development of resistance remains a major cause of concern. Epidermal growth factor receptor (EGFR) remains the poster boy for the use of targeted therapy, and the presence/absence of mutations in this gene has led to the development of inhibitors targeting specifi c mutations. We present the case of an advanced non-small cell lung cancer patient with EGFR T790M mutation treated with Osimertinib, a third-generation inhibitor.