Rates of disease recurrence and death following surgery remain high in early-stage non-small-cell lung cancer (NSCLC), despite adjuvant treatment and curative intent. Recently, osimertinib showed ...overwhelming evidence for disease-free survival (DFS), as demonstrated by an overall reduction in the risk of disease recurrence or death in the adjuvant setting of 80% versus control in the ADAURA study (stage IB-IIIA; hazard ratio 0.20; 99.12% confidence interval 0.14-0.30; P < 0.001). However, due to the early unblinding of ADAURA and lack of mature overall survival data, there is a need to qualitatively confirm consensus on the clinical and patient relevance of DFS.
We conducted a modified Delphi panel study consisting of two rounds of surveys, followed by a consensus meeting. An international panel of experts in the field of NSCLC and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (n = 13) was asked to rate agreement and comment on a list of pre-defined statements covering key consensus gaps. Statements were eliminated or updated between surveys, depending on the level of agreement. A final list of agreed-upon statements was drafted in the consensus meeting.
Consensus was reached on 32 qualitative statements, with topics including unmet needs in early-stage NSCLC, the value of DFS, and the value of osimertinib. Crucially, DFS was agreed to be a clinically and patient-relevant endpoint in adjuvant NSCLC. The relevance of DFS was found to relate to the ability of an adjuvant therapy, such as osimertinib, to keep patients in the clinically valuable curative intent setting, while preventing the burden associated with distant and locoregional recurrence, and progressive disease.
Addressing the need for measures that reflect clinical benefit is essential to continue improving outcomes for NSCLC patients. To that end, this work provides a qualitative framework for clinicians to consider the clinical and patient relevance of DFS in adjuvant NSCLC and the benefit demonstrated in ADAURA thus far.
•There is a need for qualitative consensus assessment of the clinical and patient relevance of DFS in the adjuvant setting.•An international panel of experts viewed DFS as a clinically and patient-relevant endpoint in adjuvant NSCLC.•DFS relevance in adjuvant therapy, e.g. osimertinib, relates to keeping early-stage patients in a curative intent setting.•Curative intent prevents or significantly delays locoregional and distant (CNS) recurrence burden and progressive disease.
To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph ...nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity.
Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration.
No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001).
We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.
Abstract The FLEX study demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival in the first-line treatment of patients with advanced non-small cell lung ...cancer (NSCLC). In the FLEX intention to treat (ITT) population, we investigated the prognostic significance of particular baseline characteristics. Individual patient data from the treatment arms of the ITT population of the FLEX study were combined. Univariable and multivariable Cox regression models were used to investigate variables with potential prognostic value. The ITT population comprised 1125 patients. In the univariable analysis, longer median survival times were apparent for females compared with males (12.7 vs 9.3 months); patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 compared with 1 compared with 2 (13.5 vs 10.6 vs 5.9 months); never smokers compared with former smokers compared with current smokers (14.6 vs 11.1 vs 9.0); Asians compared with Caucasians (19.5 vs 9.6 months); patients with adenocarcinoma compared with squamous cell carcinoma (12.4 vs 9.3 months) and those with metastases to one site compared with two sites compared with three or more sites (12.4 months vs 9.8 months vs 6.4 months). Age (<65 vs ≥65 years), tumor stage (IIIB with pleural effusion vs IV) and percentage of tumor cells expressing EGFR (<40% vs ≥40%) were not identified as possible prognostic factors in relation to survival time. In multivariable analysis, a stepwise selection procedure identified age (<65 vs ≥65 years), gender, ECOG PS, smoking status, region, tumor histology, and number of organs involved as independent factors of prognostic value. In summary, in patients with advanced NSCLC enrolled in the FLEX study, and consistent with previous analyses, particular patient and disease characteristics at baseline were shown to be independent factors of prognostic value. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798.
Background: Elderly cancer patients are often excluded from clinical trials and no data are available on the impact of chemotherapy-related anemia on their functional status and cognitive functions. ...This observational study investigates the association between hemoglobin (Hb) level and comprehensive geriatric assessment (CGA) variables (MMSE, ADL/IADL, GDS, CIRS and VAS). Patients and methods: We enrolled 42 consecutive lung cancer elderly patients undergoing chemotherapy that were evaluated at baseline and after each CT cycle at least until cycle 2. Hb association with CGA indexes was expressed using Spearman's non-parametric coefficient r. Results: Higher Hb values were significantly associated with more favourable values of all indexes measuring mental and functional capacity, depression and comorbidities. For all indexes except IADL, improvements from baseline were significantly related with concomitant Hb increases. In 14 patients given erythropoietin during the first two cycles, mean Hb increased from 9.2 to 10.8 g/dl, and the mean values of all CGA indexes were improved. On the contrary, in 18 patients not given erythropoietin, Hb varied from 13.0 to 11.2 g/dl and a parallel worsening in all CGA indexes was observed. Conclusions: Chemotherapy-related anemia is associated with impairment of functional status and cognitive functions. In elderly cancer patients anemia correction or maintenance could be useful to preserve functional independency and protect from mental decay. However, the study results need to be confirmed on a larger series of patients within a controlled clinical trial.
Background: Platinum-based combination chemotherapy is currently recommended as the standard treatment for patients with advanced non-small-cell lung cancer (NSCLC), but its benefit seems limited to ...fit patients with a performance status (PS) of 0 or 1. For PS2 patients, there is no consensus on standard treatment. With the aims of reviewing the evidence supporting each of these therapeutic options, possibly reaching a consensus for treatment of PS2 patients affected by advanced NSCLC in clinical practice, and suggesting the priorities for clinical research in this field, an European Experts Panel took place in Avellino, Italy in April 2003. Results and conclusions On the basis of current evidence, chemotherapy treatment appears justified for patients with advanced NSCLC and PS2. Single-agent chemotherapy (gemcitabine, vinorelbine, taxanes) could be the preferred option, although carboplatin-based or low-dose cisplatin-based doublets may represent alternative options. Stronger evidence is expected from new clinical research specifically focused on PS2 patients. Single-agent chemotherapy should be the standard arm against which experimental treatments are tested in randomised trials dedicated to PS2 patients. High priority should be given to the evaluation of tolerability and efficacy of platinum-based combinations, and to the testing of new biological agents. Another research priority is the improvement of supportive care. Patients strongly need symptomatic improvement: end points such as symptom relief, clinical benefit and quality of life should have a central position in trials dedicated to PS2 NSCLC patients.
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