scholarly journals Paradigm shift in the management of metastatic Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Ruby Gupta ◽  
Melanie Smalley ◽  
Nwabundo Anusim ◽  
Vishal Jindal ◽  
Mandeep Singh Rahi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Paradigm Shift ◽  
Survival Rates ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Cancer Management ◽  
Chemotherapeutic Approach

Background: Lung cancer is one of the leading causes of cancer mortality in the US. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced non-small cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations while patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods: Published studies included in Medline (via PubMed) and National Comprehensive Cancer Network Guidelines were reviewed for data gathering. Conclusion: The use of next generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune check point inhibitors (ICI) leading to better survival rates and lesser toxicity.

scholarly journals Paradigm shift in the management of metastatic Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Ruby Gupta ◽  
Melanie Smalley ◽  
Nwabundo Anusim ◽  
Vishal Jindal ◽  
Mandeep Singh Rahi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Paradigm Shift ◽  
Survival Rates ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Cancer Management ◽  
Chemotherapeutic Approach

Background: Lung cancer is one of the leading causes of cancer mortality in the US. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced non-small cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations while patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. Aims: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. Materials and methods: Published studies included in Medline (via PubMed) and National Comprehensive Cancer Network Guidelines were reviewed for data gathering. Conclusion: The use of next generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune check point inhibitors (ICI) leading to better survival rates and lesser toxicity.

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luiz Henrique Araujo ◽  
Bianca Mendes Souza ◽  
Laura Rabelo Leite ◽  
Sabrina A. F. Parma ◽  
Natália P. Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Nsclc Patients

Abstract Background KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory. Methods CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results The dataset comprised 4897 CRC and 4686 NSCLC samples. Among CRC samples, KRAS was mutated in 2354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (14.9%) and G12V in 522 (10.7%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p = 0.003), however this difference was exclusive of non-G12C mutants (p < 0.001). KRAS mutation frequency was lower in the South and North regions (p = 0.003), but again KRAS G12C did not differ significantly (p = 0.80). In NSCLC, KRAS mutations were found in 1004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p = 0.012), and lower in patients younger than 50 years (p < 0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 1 CRC (0.6%) cases had relevant co-mutations. Conclusions KRAS G12C presents in frequencies higher than several other driver mutations, and may represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

scholarly journals Recent advances in the management of non-small cell lung cancer

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2110 ◽  
Author(s):  
Samira Shojaee ◽  
Patrick Nana-Sinkam
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Surgical Approaches ◽  
Small Cell Lung ◽  
Cancer Management ◽  
Recent Advances ◽  
Improved Outcomes ◽  
Significant Step

Lung cancer is the number one cause of cancer-related death in both men and women. However, over the last few years, we have witnessed improved outcomes that are largely attributable to early detection, increased efforts in tobacco control, improved surgical approaches, and the development of novel targeted therapies. Currently, there are several novel therapies in clinical practice, including those targeting actionable mutations and more recently immunotherapeutic agents. Immunotherapy represents the most significant step forward in eradicating this deadly disease. Given the ever-changing landscape of lung cancer management, here we present an overview of the most recent advances in the management of non-small cell lung cancer.

Phase III Trial Comparing Oral S-1 Plus Carboplatin With Paclitaxel Plus Carboplatin in Chemotherapy-Naïve Patients With Advanced Non–Small-Cell Lung Cancer: Results of a West Japan Oncology Group Study

2010 ◽  
Vol 28 (36) ◽  
pp. 5240-5246 ◽  
Author(s):  
Isamu Okamoto ◽  
Hiroshige Yoshioka ◽  
Satoshi Morita ◽  
Masahiko Ando ◽  
Koji Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Area Under The Curve ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Open Label ◽  
Phase Iii Trial

Purpose The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days. Results At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm. Conclusion Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.

scholarly journals Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

2020 ◽  
Author(s):  
Luiz H. Araujo ◽  
Bianca Souza ◽  
Laura Leite ◽  
Sabrina Parma ◽  
Natália Lopes ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Molecular Profile ◽  
Common Mutation ◽  
Small Cell Lung ◽  
The South ◽  
Kras Mutations

Abstract Background: KRAS is the most frequently mutated oncogene in cancer, however efforts to develop targeted therapies have been largely unsuccessful. Recently, two small-molecule inhibitors, AMG 510 and MRTX849, have shown promising activity in KRAS G12C-mutant solid tumors. The current study aims to assess the molecular profile of KRAS G12C in colorectal (CRC) and non-small-cell lung cancer (NSCLC) tested in a clinical certified laboratory.Methods: CRC and NSCLC samples submitted for KRAS testing between 2017 and 2019 were reviewed. CRC samples were tested for KRAS and NRAS by pyrosequencing, while NSCLC samples were submitted to next generation sequencing of KRAS, NRAS, EGFR, and BRAF. Results: The dataset comprised 4,897 CRC and 4,686 NSCLC samples. Among CRC samples, KRAS was mutated in 2,354 (48.1%). Most frequent codon 12 mutations were G12D in 731 samples (15.2%) and G12V in 462 (9.6%), followed by G12C in 167 (3.4%). KRAS mutations were more frequent in females than males (p=0.003), however this difference was exclusive of non-G12C mutants (p<0.001). KRAS mutation frequency was lower in the South and North regions (p=0.003), but again KRAS G12C did not differ significantly (p=0.80). In NSCLC, KRAS mutations were found in 1,004 samples (21.4%). As opposed to CRC samples, G12C was the most common mutation in KRAS, in 346 cases (7.4%). The frequency of KRAS G12C was higher in the South and Southeast regions (p=0.012), and lower in patients younger than 50 years (p<0.001). KRAS G12C mutations were largely mutually exclusive with other driver mutations; only 11 NSCLC (3.2%) and 3 CRC (1.8%) cases had relevant co-mutations. Conclusions: KRAS G12C presents in frequencies higher than several other driver mutations, represent a large volume of patients in absolute numbers. KRAS testing should be considered in all CRC and NSCLC patients, independently of clinical or demographic characteristics.

Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group phase II study 8805.

1995 ◽  
Vol 13 (8) ◽  
pp. 1880-1892 ◽  
Author(s):  
K S Albain ◽  
V W Rusch ◽  
J J Crowley ◽  
T W Rice ◽  
A T Turrisi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Survival Rates ◽  
Small Cell ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Term Survival ◽  
Southwest Oncology Group

PURPOSE To assess the feasibility of concurrent chemotherapy and irradiation (chemoRT) followed by surgery in locally advanced non-small-cell lung cancer (NSCLC) in a cooperative group setting, and to estimate response, resection rates, relapse patterns, and survival for stage subsets IIIA(N2) versus IIIB. PATIENTS AND METHODS Biopsy proof of either positive N2 nodes (IIIAN2) or of N3 nodes or T4 primary lesions (IIIB) was required. Induction was two cycles of cisplatin and etoposide plus concurrent chest RT to 45 Gy. Resection was attempted if response or stable disease occurred. A chemoRT boost was given if either unresectable disease or positive margins or nodes was found. RESULTS The median follow-up time for 126 eligible patients [75 stage IIIA(N2) and 51 IIIB] was 2.4 years. The objective response rate to induction was 59%, and 29% were stable. Resectability was 85% for the IIIA(N2) group eligible for surgery and 80% for the IIIB group. Reversible grade 4 toxicity occurred in 13% of patients. There were 13 treatment-related deaths (10%) and 19 others (15%) died of causes not related to toxicity or tumor. Of 65 relapses, 11% were only locoregional and 61% were only distant. There were 26 brain relapses, of which 19 were the sole site or cause of death. There was no survival difference (P = .81) between stage IIIA(N2) versus stage IIIB (median survivals, 13 and 17 months; 2-year survival rates, 37% and 39%; 3-year survival rates, 27% and 24%). The strongest predictor of long-term survival after thoracotomy was absence of tumor in the mediastinal nodes at surgery (median survivals, 30 v 10 months; 3-year survival rates, 44% v 18%; P = .0005). CONCLUSION This trimodality approach was feasible in this Southwest Oncology Group (SWOG) study, with an encouraging 26% 3-year survival rate. An Intergroup study is currently being conducted to determine whether surgery adds more to the risk or to the benefit of chemoRT.

Systemic and Radiation Therapy Approaches for Locally Advanced Non–Small-Cell Lung Cancer

2022 ◽  
Author(s):  
Kristin A. Higgins ◽  
Sonam Puri ◽  
Jhanelle E. Gray
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Circulating Tumor Dna ◽  
Small Cell ◽  
Concurrent Chemoradiation ◽  
Driver Mutations ◽  
Small Cell Lung

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.

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