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Improving Outcomes in Advanced Lung Cancer: Maintenance therapy in non-small-cell lung carcinoma.

ABSTRACT: Systemic chemotherapy has remained the traditional treatment for metastatic non-small-cell lung carcinoma (NSCLC), enhancing survival rate at 1 year to 29%. The median survival had plateaued at around 10 months until early 2008, and in an attempt to enhance survival in advanced disease, maintenance chemotherapy trials were initiated which had recently demonstrated prolongation of survival by an additional 2-3 months in patients who had performance status (PS) 0-1 and well-preserved organ functions. Suitable patients with any degree of clinical benefit are treated with 4-6 cycles, and then one of the active agents is continued until best response, or toxicity (continued maintenance), or changed to a cross non-resistant single agent (switch maintenance). The article briefly reviews the evolution of systemic therapy and describes key randomised trials of maintenance therapy instituting chemotherapy and targeted agents in an attempt to improve outcomes in advanced metastatic NSCLC, based on certain clinical features, histology, and genetics.

SUBMITTER: Furrukh M

PROVIDER: S-EPMC3616797 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Improving Outcomes in Advanced Lung Cancer: Maintenance therapy in non-small-cell lung carcinoma.

Furrukh Muhammad M Burney Ikram A IA Kumar Shiyam S Zahid Khwaja F KF Al-Moundhri Mansour M

Sultan Qaboos University medical journal 20130227 1

Systemic chemotherapy has remained the traditional treatment for metastatic non-small-cell lung carcinoma (NSCLC), enhancing survival rate at 1 year to 29%. The median survival had plateaued at around 10 months until early 2008, and in an attempt to enhance survival in advanced disease, maintenance chemotherapy trials were initiated which had recently demonstrated prolongation of survival by an additional 2-3 months in patients who had performance status (PS) 0-1 and well-preserved organ functio ...[more]

PMID: 23573377

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Project description:IntroductionAdvanced non-small cell lung cancer (NSCLC) is a severe disease with burdensome symptoms and traditionally poor outcomes. The treatment of advance disease is based on chemotherapy, with the recent addition of immunotherapy. Patients who respond to initial treatment can opt to receive maintenance therapy (MT). It is important to understand why patients with advanced NSCLC choose to accept or refuse therapy, and how physician recommendations play into this decision-making process. This study characterized patient and physician decision-making regarding treatment for patients with advanced non-squamous NSCLC in the USA using the example of MT.Methods and materialsThis study employed multiple approaches: patient interviews, a patient survey, and a physician survey. Qualitative interviews were conducted among patients who had been offered MT to identify factors influencing treatment decision-making. The patient survey explored the decision-making process and quantified challenges and motivators for receiving MT. The physician survey included a discrete choice experiment to understand the relationship between physician treatment recommendations and patient characteristics.ResultsInterviewed patients (n = 10) were motivated to receive MT in the hope of extending their lives and being proactive against their cancer, and they anticipated reduced adverse effects compared with first-line therapy. Surveyed patients (n = 77) described several deterrents to receiving therapy; the most prominent was severity of adverse effects, which was an influencing factor for 34% of patients. The major motivator for receiving therapy was the potential to extend life, which influenced 97% of patients. A total of 100 oncologists participated in the physician survey. Patients' lack of treatment motivation/inconvenience, disease progression, presence of severe renal co-morbidities, and older age decreased the likelihood of physicians recommending the use of MT.ConclusionThis study identified challenges and motivators influencing advanced NSCLC patients' decisions to accept or refuse therapy, as well as patient and disease characteristics associated with physician's treatment recommendations for MT.

Project description:BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), gefitinib and erlotinib have been tested as maintenance therapy in patients with advanced non-small-cell lung cancer (NSCLC). The studies are quite heterogenous regarding study size and populations, and a synopsis of these data could give some more insight in the role of maintenance therapy with TKI.MethodsIn September 2012 we performed a search in the pubmed, EMBASE and Cochrane library databases for randomized phase III trials exploring the role of gefitinib or erlotinib in advanced non-small cell lung cancer. Through a rigorous selection process with specific criteria, five trials (n = 2436 patients) were included for analysis. Standard statistical methods for meta-analysis were applied.ResultsTKIs (gefitinib and erlotinib) significantly increased progression-free survival (PFS) [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.50-0.76, I(2) = 78.1%] and overall survival (HR 0.84, 95% CI 0.76-0.93, I(2) = 0.0%) compared with placebo or observation. The PFS benefit was consistent in all subgroups including stage, sex, ethnicity, performance status, smoking status, histology, EGFR mutation status, and previous response to chemotherapy. Patients with clinical features such as female, never smoker, adenocarcinoma, Asian ethnicity and EGFR mutation positive had more pronounced PFS benefit. Overall survival benefit was observed in patients with clinical features such as female, non-smoker, smoker, adenocarcinoma, and previous stable to induction chemotherapy. Severe adverse events were not frequent. Main limitations of this analysis are that it is not based on individual patient data, and not all studies provided detailed subgroups analysis.ConclusionsThe results show that maintenance therapy with erlotinib or gefitinib produces a significant PFS and OS benefit for unselected patients with advanced NSCLC compared with placebo or observation. Given the less toxicity of TKIs than chemotherapy and simple oral administration, this treatment strategy seems to be of important clinical value.

Project description:BackgroundWith the identification of new targetable drivers and the recent emergence of novel targeted drugs, using comprehensive genomic profiling in lieu of the routine testing for classic drivers in the clinical care for advanced NSCLC has been increasingly advocated. However, the key assumption justifying this practice, that comprehensive genomic profiling could lead to effective anticancer therapies and improve patient outcomes, remains unproved.MethodsComprehensive genomic profiling was prospectively applied in 1564 advanced NSCLC patients to identify potentially actionable genomic alterations. Patients were assigned to genotype-matched targeted therapies or nonmatched therapies based on the profiling results. Its utility in directing treatments was determined by the proportion of patients receiving genotype-matched targeted therapies and the proportion of patients being enrolled into genotype-matched clinical trials. Its impacts on patient outcomes were assessed by comparing progression-free survival (PFS) and overall survival (OS) between patients who received a genotype-matched and nonmatched therapy.ResultsFrom October 2016 to October 2019, tumor genomic profiles were established in 1166 patients, leading to a matched targeted therapy in 37.7% (n = 440) and a genotype-matched trial enrollment in 20.9% of patients (n = 244). Potentially actionable alterations were detected in 781 patients (67.0%). For these patients, a genomic profiling-directed matched therapy significantly improved PFS (9.0 months vs 4.9 months, P < 0.001) and OS (3.9 years vs 2.5 years, P < 0.001) compared with a nonmatched therapy. Excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. No PFS (4.7 months vs 4.6 months, P = 0.530) or OS (1.9 years vs 2.4 years, P = 0.238) benefit was observed with the use of genotype-matched targeted therapies in this population.ConclusionsComprehensive genomic profiling is of clinical utility in assisting treatment selection, facilitating clinical trial enrollment, and improving patient outcomes in advanced NSCLC. However, for patients carrying alterations without standard-of-care targeted drugs, the interpretation of genomic profiling results should be careful given the low likelihood of benefit from the investigational or off-label use of targeted therapies in this population in the current treatment landscape.Trial registrationChiCTR1900027582 (retrospectively registered on 19 November 2019).

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Improving Outcomes in Advanced Lung Cancer: Maintenance therapy in non-small-cell lung carcinoma.

Publications

Improving Outcomes in Advanced Lung Cancer: Maintenance therapy in non-small-cell lung carcinoma.

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