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      Treatment Decisions for Advanced Non-Squamous Non-Small Cell Lung Cancer: Patient and Physician Perspectives on Maintenance Therapy

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          Abstract

          Introduction

          Advanced 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 Materials

          This 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.

          Results

          Interviewed 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.

          Conclusion

          This 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.

          Electronic supplementary material

          The online version of this article (10.1007/s40271-018-0327-3) contains supplementary material, which is available to authorized users.

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          Most cited references13

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          PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

          In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data. In all, 939 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m(2) on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.
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            Treatment paradigms for patients with metastatic non-small-cell lung cancer: first-, second-, and third-line.

            N B Leighl (2012)
            Metastatic non-small-cell lung cancer (nsclc) is the leading cause of cancer mortality in Canada. Although treatment outcomes in advanced disease remain modest, with paradigm shifts in the approach to treatment, they are steadily improving. Customizing treatment based on histology and molecular typing has become the standard of care. EGFR genotyping and pathology subtyping should be considered routine in new diagnoses of metastatic nsclc. Treatment options for those with somatic EGFR activating mutations include gefitinib until progression, followed by standard chemotherapy. For patients with wild-type EGFR, or in patients whose EGFR genotype is unknown, platinum-based chemotherapy remains the first-line standard, with single-agent chemotherapy as an option for older patients and those who are unfit for platinum-doublet therapy. Patients with nonsquamous histology may receive treatment regimens incorporating pemetrexed or bevacizumab. In patients with squamous cell carcinoma, the latter agents should be avoided because of concerns about enhanced toxicity or decreased efficacy. Second-line chemotherapy is offered to a selected subgroup of patients upon progression and may include pemetrexed in non-squamous histology and docetaxel or erlotinib (or both) in all histologies. Currently, only erlotinib is offered as a third-line option in unselected nsclc patients after failure of first- and second-line chemotherapy. Maintenance therapy is emerging as a new option for patients, as are targeted therapies for particular molecular subtypes of nsclc, such as crizotinib in tumours harbouring the EML4-ALK gene rearrangement.
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              Health-related quality of life in advanced non-small cell lung cancer: correlates and comparisons to normative data.

              The aim was to describe self-reported health-related quality of life (HRQoL) in patients with advanced non-small cell lung cancer and to investigate the associations to stage of disease, age, gender, weight loss and performance status. Further, the study aimed to compare patients' HRQoL with that of the Swedish general population. Data on HRQoL were collected within a multi-centre randomised controlled trial. A total of 334 patients were included between 1998 and 2001. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Lung Cancer Questionnaire (EORTC QLQ-LC13) were used to assess HRQoL. HRQoL data for comparison with the Swedish population were derived from a random sample of the Swedish population. Patients reported a markedly impaired HRQoL compared to the normal population. There were statistically and clinically significant differences with regard to almost all QLQ-C30 functional and symptom scales. Global health status, physical functioning, role functioning and emotional functioning were markedly deteriorated. The most prominent symptoms were dyspnoea, fatigue, coughing, insomnia, appetite loss and pain. A low performance status, younger age, female gender and a more advanced disease were independently associated with a worse HRQoL. Additional studies are required to gain increased insight into this seriously ill group of patients and their need of supportive care.
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                Author and article information

                Contributors
                1-604-235-2172 , Kerstin.Mueller@iconplc.com
                Journal
                Patient
                Patient
                The Patient
                Springer International Publishing (Cham )
                1178-1653
                1178-1661
                21 August 2018
                21 August 2018
                2019
                : 12
                : 2
                : 223-233
                Affiliations
                [1 ]ICON Plc, Vancouver, BC Canada
                [2 ]ISNI 0000 0000 2220 2544, GRID grid.417540.3, Eli Lilly and Company, ; Indianapolis, IN USA
                [3 ]GRID grid.468189.a, Levine Cancer Institute, Atrium Health, ; Charlotte, NC USA
                [4 ]GRID grid.416167.3, Mount Sinai Health Systems, ; New York, NY USA
                [5 ]GRID grid.416125.5, Cone Health, ; Greensboro, NC USA
                [6 ]ISNI 0000 0004 0615 4027, GRID grid.492834.0, Oncology Hematology Care (OHC), ; Cincinnati, OH USA
                [7 ]ISNI 0000 0001 1456 7807, GRID grid.254444.7, Karmanos Cancer Institute, ; Detroit, MI USA
                Author information
                http://orcid.org/0000-0003-3315-4674
                Article
                327
                10.1007/s40271-018-0327-3
                6397138
                30128728
                a4d93854-99aa-4471-842e-14e1de0c7d2b
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: FundRef https://dx.doi.org/10.13039/100004312, Eli Lilly and Company;
                Categories
                Original Research Article
                Custom metadata
                © Springer Nature Switzerland AG 2019

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