Clinical characteristic and survival outcomes of patients with advanced NSCLC according to KRAS mutational status in the French real-life ESME cohort.

PURPOSE: The RAS/MEK signaling pathway is essential in carcinogenesis and frequently altered in non-small-cell lung cancer (NSCLC), notably by KRAS mutations (KRASm) that affect 25%-30% of non-squamous NSCLC. This study aims to explore the impact of KRASm subtypes on disease phenotype and survival outcomes. PATIENTS AND METHODS: We conducted a retrospective analysis of the French Epidemiological Strategy and Medical Economics database for advanced or metastatic lung cancer from 2011 to 2021. Patient demographics, histology, KRASm status, treatment strategies, and outcomes were assessed. RESULTS: Of 10 177 assessable patients for KRAS status, 17.6% had KRAS p.G12C mutation, 22.6% had KRAS non-p.G12C mutation, and 59.8% were KRASwt. KRASm patients were more often smokers (96.3%) compared with KRASwt (85.8%). A higher proportion of programmed death-ligand 1 ≥50% was found for KRASm patients: 43.5% versus 38.0% (P < 0.01). KRASm correlated with poorer outcomes. First-line median progression-free survival was shorter in the KRASm than the KRASwt cohort: 4.0 months [95% confidence interval (CI) 3.7-4.3 months] versus 5.1 months (95% CI 4.8-5.3 months), P < 0.001. First-line overall survival was shorter for KRASm than KRASwt patients: 12.6 months (95% CI 11.6-13.6 months) versus 15.4 months (95% CI 14.6-16.2 months), P = 0.012. First-line chemoimmunotherapy offered better overall survival in KRAS p.G12C (48.8 months) compared with KRAS non-p.G12C (24.0 months) and KRASwt (22.5 months) patients. Second-line overall survival with immunotherapy was superior in the KRAS p.G12C subgroup: 12.6 months (95% CI 8.1-18.6 months) compared with 9.4 months (95% CI 8.0-11.4 months) for KRAS non-p.G12C and 9.6 months (8.4-11.0 months) for KRASwt patients. CONCLUSION: We highlighted distinct clinical profiles and survival outcomes according to KRASm subtypes. Notably KRAS p.G12C mutations may provide increased sensitivity to immunotherapy, suggesting potential therapeutic implications for sequencing or combination of therapies. Further research on the impact of emerging KRAS specific inhibitors are warranted in real-world cohorts.

[Assessment of a tool for decision making in case of worsening condition of cancer patients]. / Évaluation d'une fiche d'aide à la décision en cas d'aggravation d'un patient cancéreux.

BACKGROUND: In response to questions regarding the appropriate intensity of care for some patients, "a decision support aid regarding the intensity of care in case of worsening condition of a patient with a chronic disease" has been established at the Grenoble university hospital. According to patient's wishes and the experience of the medical and paramedical team who are responsible for him, a level of intensity of care will be suggested. METHODS: We propose a prospective and multicenter study conducted in the Rhône-Alpes-Auvergne area. All lung cancer patients admitted to a pulmonology unit in 2014 would be included. This document would be used if a decision to withhold life-sustaining treatment exists. We would assess the relationship between the planned intensity of care and those established when the patient develops organ failure. Patient characteristics and factors associated with proposed levels and types of care would be analyzed. Patient and family opinions will be obtained at 3 months. The number of subjects to be included is 468. EXPECTED RESULTS: Therefore, we hope to be able to define the wishes of patients' and to propose an appropriate and adapted aid for decisions if they develop organ failure.

Cost-minimization analysis of a phase III trial comparing concurrent versus sequential radiochemotherapy for locally advanced non-small-cell lung cancer (GFPC-GLOT 95-01).

BACKGROUND: We conducted an economic analysis of a phase III clinical trial comparing sequential radiochemotherapy (RT-CT) with concurrent RT-CT in patients with locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: The trial was a randomized multicenter study comparing three cycles of chemotherapy (arm A) followed by radiotherapy against an RT-CT combination (two cycles of platinum etoposide) followed by two cycles of platinum-vinorelbine (arm B). The economic analysis adopted the payer's perspective and only included direct costs. Costs (euro, 1996-2003) were recorded until the cut-off date. A cost minimization analysis and a sensitivity analysis were carried out. RESULTS: Data from 173 patients were used in the economic study. Protocol costs tended to be higher in arm B, while relapse costs were significantly higher in arm A. The total number of hospital days was higher in arm B. The average total cost per patient was euro16,074 in arm A and euro15,245 in arm B (P=0.15). The cost minimization analysis favored arm B. This advantage persisted in the sensitivity analysis. CONCLUSIONS: Concurrent RT-CT was not the more costly strategy in this phase III trial, despite lengthier hospitalization for toxicity. Other studies of similar design are needed to confirm these results in future randomized trials.

Cost analysis of hospital treatment--two chemotherapic regimens for non-surgical non-small cell lung cancer. GFPC (Groupe Français Pneumo Cancérologie)

STUDY OBJECTIVES: compare the costs of two regimens of chemotherapy. Apply weighted costs to an economic model in a hospital perspective. DESIGN: prospective randomized study of two groups of patients receiving: branch B, mitomycin-navelbine-cisplatin (MNP); branch A, mitomycin-vindesine-cisplatin (MVP). SETTING: pneumologic units of University and non-University hospitals. METHODS: clinical evaluation during chemotherapy incorporated events enabling construction of an event tree. Direct hospital costs included those of: cytostatic agents, materials used and nursing time; costs of side-effects (medical and paramedical time, diagnostic and therapeutic examinations). Effectiveness was measured in terms of response rates. PATIENTS: 209 patients were included, 100 in arm B, 109 in arm A. RESULTS: the response rates were 25% in branch B, 17% in branch A. In the hypothesis of equivalence of the two strategies, we compared only overall mean cost per patient. Despite the fact arm B needed more hospital injections, the difference was low (+4.6%). For a difference in effectiveness, the opposite was observed for the average cost-effectiveness ratio: arm B was less costly (-12 339.40 FF for a responder). CONCLUSION: incorporation of economic parameters was found to have a bearing on the choice of chemotherapeutic regimen for the treatment of non-small cell lung cancer. Economic analyses of this kind can provide useful extra information for rational therapeutic decisions.

[Clinical and economic evaluation of the initial assessment of small cell cancer of the lung. Alternatives to classic evaluation. LGTO. The Lyon Group of Thoracic Oncology]. / Evaluation clinique et économique du bilan initial des cancers du poumon à petites cellules. Alternatives à un bilan classique. GLOT. Groupe Lyonnais d'Oncologie Thoracique.

Alternatively to the usual evaluation summary, a characteristic of small cell lung cancer, is the probability of significant diffuse metastases; the prognosis is directly linked to the extent of these metastases. Moreover, the assessment of the initial extension becomes heavier and more costly as investigations continue and each new technology appears. In order to evaluate the contribution of each examination, a classification has been established as a function of the time-scale to obtain the results, of the technology involved, or whether the investigation is painful or not and any likelihood of iatrogenic side-effects. An assessment in three stages is proposed to achieve the most effective and cheapest diagnosis possible. In relation to the usual technique of assessment this sequential approach allows for a 27% reduction in the time-scale for the diagnosis of diffuse disease, 51.3% in terms of technical involvement, 46.3% in terms of pain and discomfort and 53.9% in terms of iatrogenic potential. At the same time a reduction in cost of 47.5% is observed.