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Square peg, round hole? Programmed death-1 inhibitors in epidermal growth factor receptor-mutant non-small cell lung cancer.

ABSTRACT:

SUBMITTER: Gainor JF

PROVIDER: S-EPMC5863154 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Square peg, round hole? Programmed death-1 inhibitors in epidermal growth factor receptor-mutant non-small cell lung cancer.

Gainor Justin F JF

Journal of thoracic disease 20180101 1

PMID: 29600014

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Project description:BackgroundComorbidity of musculoskeletal (MSK) and mental health (MH) problems is common but challenging to treat using conventional approaches. Integration of conventional with complementary approaches (CAM) might help address this challenge. Integration can aim to transform biomedicine into a new health paradigm or to selectively incorporate CAM in addition to conventional care. This study explored professionals' experiences and views of CAM for comorbid patients and the potential for integration into UK primary care.MethodsWe ran focus groups with GPs and CAM practitioners at three sites across England and focus groups and interviews with healthcare commissioners. Topics included experience of co-morbid MSK-MH and CAM/integration, evidence, knowledge and barriers to integration. Sampling was purposive. A framework analysis used frequency, specificity, intensity of data, and disconfirming evidence.ResultsWe recruited 36 CAM practitioners (4 focus groups), 20 GPs (3 focus groups) and 8 commissioners (1 focus group, 5 interviews). GPs described challenges treating MSK-MH comorbidity and agreed CAM might have a role. Exercise- or self-care-based CAMs were most acceptable to GPs. CAM practitioners were generally pro-integration. A prominent theme was different understandings of health between CAM and general practitioners, which was likely to impede integration. Another concern was that integration might fundamentally change the care provided by both professional groups. For CAM practitioners, NHS structural barriers were a major issue. For GPs, their lack of CAM knowledge and the pressures on general practice were barriers to integration, and some felt integrating CAM was beyond their capabilities. Facilitators of integration were evidence of effectiveness and cost effectiveness (particularly for CAM practitioners). Governance was the least important barrier for all groups. There was little consensus on the ideal integration model, particularly in terms of financing. Commissioners suggested CAM could be part of social prescribing.ConclusionsCAM has the potential to help the NHS in treating the burden of MSK-MH comorbidity. Given the challenges of integration, selective incorporation using traditional referral from primary care to CAM may be the most feasible model. However, cost implications would need to be addressed, possibly through models such as social prescribing or an extension of integrated personal commissioning.

Project description:BackgroundThe role of adding immune checkpoint inhibitors to chemotherapy in tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) remains unknown. We carried out a meta-analysis to comprehensively assess the role of chemoimmunotherapy combinations, with and without vascular endothelial growth factor (VEGF) inhibition, in TKI-resistant, EGFR-mutant NSCLC.Materials and methodsWe systemically searched PubMed/MEDLINE and the proceedings of key annual meetings between 2018 and 2024 to identify randomized studies that evaluated chemoimmunotherapy combinations and included patients with EGFR-mutant NSCLC. Six randomized, phase III trials (CheckMate-722, KEYNOTE-789, ORIENT-31, IMpower150, IMpower151, and ATTLAS) were included in the meta-analysis. To compare progression-free survival (PFS) and overall survival (OS) outcomes, we extracted hazard ratio (HR) and 95% confidence interval (CI) for PFS and OS for EGFR-mutant subgroups from each study. We used the fixed effects model with inverse variance weighting to estimate the overall effect sizes for PFS and OS for chemoimmunotherapy combinations (with and without VEGF inhibitors) versus control arms.ResultsA total of 1772 patients with EGFR-mutant NSCLC were included. Adding programmed death-ligand 1 [PD-(L)1] inhibitors to chemotherapy significantly improved PFS (HR 0.77, 95% CI 0.67-0.88, P = 0.0002). This effect was greater when both PD-(L)1 and VEGF inhibition were utilized (PFS: HR 0.62, 95% CI 0.52-0.73, P < 0.0001). The pooled OS HR was 0.86 (95% CI 0.75-1.00, P = 0.0429) with the chemotherapy + PD-(L)1 combinations and 0.98 (95% CI 0.79-1.22, P = 0.8463) with dual PD-(L)1/VEGF inhibition.ConclusionsDespite modest improvements in PFS, most pronounced when both PD-(L)1 and VEGF inhibitors are added to chemotherapy, neither strategy led to clinically meaningful improvements in OS. Our results do not support the broad use of chemoimmunotherapy combinations in TKI-resistant, EGFR-mutant lung cancer. Novel immunotherapy approaches are urgently needed for oncogene-driven NSCLC.

Dataset Information

Square peg, round hole? Programmed death-1 inhibitors in epidermal growth factor receptor-mutant non-small cell lung cancer.

Publications

Square peg, round hole? Programmed death-1 inhibitors in epidermal growth factor receptor-mutant non-small cell lung cancer.

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