A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective

International audienceOBJECTIVES: Adjuvant chemotherapy with vinorelbine plus cisplatin (VC) improves survival in resected non-small-cell lung cancer (NSCLC), but has negative impact on quality of life (QoL). In advanced NSCLC, gemcitabine plus cisplatin (GC) and docetaxel plus cisplatin (DC) exhibit comparable efficacy, with possibly superior QoL compared to VC. This trial investigated these regimens in the adjuvant setting. METHODS: Patients with Stage IB to III NSCLC were eligible following standardized surgery. Overall, 136 patients were included, with 67 and 69 assigned to the GC and DC arms, respectively. Cisplatin (75 mg/m(2), Day [D] 1) plus gemcitabine (1250 mg/m(2), D1 and D8) or docetaxel (75 mg/m(2) D1) were administered for three cycles. Primary end-point was QoL (EORTC QLQ-C30), with the study designed to detect a 10-point difference between arms. Overall survival, safety and cost were secondary end-points. RESULTS: No between-group imbalance was observed in terms of patient characteristics. At inclusion, global health status (GHS) scores (/100) were 63.5 and 62.7 in GC and DC, respectively (P = 0.8), improving to 64.5 and 65.4 after 3 months (P = 0.8). No significant difference in functional or symptoms scores was observed between the arms except for alopecia. Grade 3/4 haematological and non-haematological toxicities were found in 33.8 and 21.7% (P = 0.11), and 33.8 and 26.1% (P = 0.33) of patients, in GC and DC, respectively. At 2 years, 92.9 and 89.8% of patients remained alive in GC and DC, respectively (P = 0.88). CONCLUSIONS: DC and GC adjuvant chemotherapies for completely resected NSCLC were well tolerated and appear free of major QoL effects, and are therefore representing candidates for comparison with the standard VC regimen

An open multicenter phase II trial of weekly docetaxel for advanced-stage non-small-cell lung cancer in elderly patients with significant comorbidity and/or poor performance status: The GFPC 02-02b study.

International audienceCONTEXT: The objective of this study was to evaluate the feasibility and activity of weekly docetaxel monotherapy in frail elderly patients with advanced-stage non-small-cell lung cancer, selected on the basis of their precise age, general condition, and number of comorbid disorders (Charlson score). METHODS: Analysis of the response rate, toxicity, quality of life, median survival and 1-year survival rates after 1-3 six-week cycles of docetaxel 30mg/m(2) weekly. RESULTS: Fifty patients were enrolled and 42 were assessable. Five patients (10%, [3.7-22.6]) had objective responses, 14 (28%, [16.9-41.6]) had stable disease, and 23 (46%, [32.6-52.8]) progressed. The main grade 3-4 toxicity was fatigue (30%). Quality of life remained stable during treatment. The median survival time was 4.3 months, and the 1-year survival rate was 21.8%. CONCLUSION: In frail elderly patients selected on the basis of their age, general condition and comorbidity, weekly docetaxel monotherapy has acceptable toxicity and does not negatively affect quality of life. In contrast, it has only moderate activity

Cost-effectiveness of second-line chemotherapy for non-small cell lung cancer: an economic, randomized, prospective, multicenter phase III trial comparing docetaxel and pemetrexed: the GFPC 05-06 study.

International audienceBACKGROUND: There are few data on the cost-effectiveness of second-line chemotherapies for non-small cell lung cancer (NSCLC). The objective of this phase III, randomized, multicenter, prospective study was to compare the cost-effectiveness of docetaxel and pemetrexed, two widely used drugs. METHODS: We compared, from a payer's perspective, the directs costs and effectiveness of docetaxel (75 mg/m, arm A) and pemetrexed (500 mg/m, arm B) administered every 3 weeks to NSCLC patients who had progressed after first-line platinum-based chemotherapy. Monthly health utilities (based on disease states: responding, stable or progressive, and grade 3/4 toxicities) were derived from the literature. Costs were prospectively assessed. RESULTS: One hundred fifty patients were enrolled between February 2006 and June 2008. The patients in the docetaxel and pemetrexed arms had similar clinical characteristics and treatment efficacy (respective objective response rates 10.7% and 12%; median progression-free survival times 2.8 and 2.5 months; median survival times 8.0 and 6.4 months, respectively). Grade 3/4 toxicities were significantly less frequent with pemetrexed (52.0% versus 33.3%, p = 0.02). Docetaxel was associated with lower treatment-period costs (€9709 ± €6272 versus €13,436 ± €6508, p < 0.001). Docetaxel had a more favorable cost-utility ratio than pemetrexed. When compared with best supportive care, the cost-utility was €32,652/quality-adjusted life year for docetaxel and €40,980/quality-adjusted life year for pemetrexed. CONCLUSION: Second-line treatment for NSCLC is more cost-effective with docetaxel than with pemetrexed. Both strategies have acceptable cost-effectiveness ratios compared with commonly used and reimbursed regimens for advanced NSCLC

Cost-Effectiveness of Second-Line Chemotherapy for Non- small Cell Lung Cancer

the 0506 GFPC Team Background: There are few data on the cost-effectiveness of second-line chemotherapies for non-small cell lung cancer (NSCLC). The objective of this phase III, randomized, multicenter, prospective study was to compare the cost-effectiveness of docetaxel and pemetrexed, two widely used drugs. Methods: We compared, from a payer&apos;s perspective, the directs costs and effectiveness of docetaxel (75 mg/m 2 , arm A) and pemetrexed (500 mg/m 2 , arm B) administered every 3 weeks to NSCLC patients who had progressed after first-line platinum-based chemotherapy. Monthly health utilities (based on disease states: responding, stable or progressive, and grade 3/4 toxicities) were derived from the literature. Costs were prospectively assessed

Combined, patient-level, analysis of two randomised trials evaluating the addition of denosumab to standard first-line chemotherapy in advanced NSCLC - The ETOP/EORTC SPLENDOUR and AMGEN-249 trials

Introduction: The efficacy of adding denosumab to standard first-line chemotherapy for advanced NSCLC patients has been evaluated in two separate randomised trials (SPLENDOUR and AMGEN-249). In this pooled analysis, we will assess the combination-treatment effect in the largest available population, in order to conclude about the potential impact of denosumab in NSCLC. Methods: Both trials included in this combined analysis, were randomised (SPLENDOUR 1:1, AMGEN-249 2:1) multi-centre trials stratified by histology, bone metastasis, geographical region and for SPLENDOUR only, ECOG PS. Cox proportional hazards models, were used to assess the treatment effect with respect to overall survival (OS; primary endpoint) and progression-free survival (PFS; secondary endpoint). Heterogeneity between trials was assessed, and subgroup analyses were performed. Results: The pooled analysis was based on 740 randomised patients (SPLENDOUR:514; AMGEN-249:226), with 407 patients in the chemotherapy-denosumab arm and 333 in the chemotherapy-alone arm. In the chemotherapy-denosumab arm, at a median follow-up of 22.0 months, 277 (68.1%) deaths were reported with median OS 9.2 months (95%CI:[8.0-10.7]), while in the chemotherapy-alone arm, with similar median follow-up of 20.3 months, 230 (69.1%) deaths with median OS 9.9 months (95%CI:[8.2-11.2]). No significant denosumab effect was found (HR = 0.98; 95%CI:[0.82-1.18]; P = 0.85). Among subgroups, interaction was found between treatment and histology subtypes (P = 0.020), with a sta-tistically significant benefit in the squamous group (HR = 0.70; 95%CI:[0.49-0.98]; P = 0.038), from 7.6 to 9.0 months median OS. With respect to PFS, 363 (89.2%) and 298 (89.5%) events were reported in the chemotherapy-denosumab and chemotherapy-alone arms, respectively, with corresponding medians 4.8 months (95%CI:[4.4-5.3]) and 4.9 months (95%CI:[4.3-5.4]). HR for PFS was 0.97 (95%CI:[0.83-1.15]; P = 0.76), indicating that no significant denosumab benefit existed for PFS. Conclusion: In this pooled analysis, no statistically significant improvement was shown in PFS/OS with the combination of denosumab and chemotherapy for advanced NSCLC and no meaningful benefit in any of the subgroups

A phase II study of cisplatin with intravenous and oral vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy with oral vinorelbine and cisplatin for locally advanced non-small cell lung cancer

BACKGROUND: Concomitant platinum-based chemotherapy and radiotherapy (CT-RT) is the recommended treatment for unresectable locally advanced stage III non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy and safety of fractionated oral vinorelbine with cisplatin as induction CT followed by CT-RT. METHODS: Patients with stage III NSCLC received 2 induction cycles of intravenous vinorelbine 25 mg/m(2) and cisplatin 80 mg/m(2) on day 1 and oral vinorelbine 60 mg/m(2) on day 8. Responding patients received 2 more cycles of cisplatin 80 mg/m(2) on day 1 and oral vinorelbine 20 mg on days 1, 3 and 5 concomitantly with radiotherapy 2 Gy daily, 5 days/week for a total of 66 Gy. RESULTS: Seventy patients, median age 61 years, were enrolled. Overall response rate (ORR) was 50.0%; Disease Control Rate was 81.42%. Median PFS was 14.58 months [95% CI, 10.97-18.75]. Median OS was 17.08 months [95% CI, 13.57-29.57]. One-year and 2-year survival rates were 68.6% [95% CI, 57.7-79.4] and 37%. One patient had a grade 3 pulmonary radiation injury and 26.5% had graded 1/2 esophagitis. CONCLUSION: In non-operable IIIA-IIIB NSCLC, the combination oral vinorelbine (fractionated fixed dose) plus cisplatin, during concomitant CT-RT, could offer a well-tolerated option, with comparable activity to I.V. vinorelbine-based chemoradiotherapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0183903

Cost-utility analysis of maintenance therapy with gemcitabine or erlotinib vs observation with predefined second-line treatment after cisplatin–gemcitabine induction chemotherapy for advanced NSCLC: IFCT-GFPC 0502-Eco phase III study

on behalf of the IFCT-GFPC investigatorsInternational audienceBackground: The IFCT-GFPC 0502 phase III study reported prolongation of progression-free survival with gemcitabine or erlotinib maintenance vs. observation after cisplatin–gemcitabine induction chemotherapy for advanced non-small-cell lung cancer (NSCLC). This analysis was undertaken to assess the incremental cost-effectiveness ratio (ICER) of these strategies for the global population and pre-specified subgroups.Methods: A cost-utility analysis evaluated the ICER of gemcitabine or erlotinib maintenance therapy vs. observation, from randomization until the end of follow-up. Direct medical costs (including drugs, hospitalization, follow-up examinations, second-line treatments and palliative care) were prospectively collected per patient during the trial, until death, from the primary health-insurance provider's perspective. Utility data were extracted from literature. Sensitivity analyses were conducted.Results: The ICERs for gemcitabine or erlotinib maintenance therapy were respectively 76,625 and 184,733 euros per quality-adjusted life year (QALY). Gemcitabine continuation maintenance therapy had a favourable ICER in patients with PS = 0 (52,213 €/QALY), in responders to induction chemotherapy (64,296 €/QALY), regardless of histology (adenocarcinoma, 62,292 €/QALY, non adenocarcinoma, 83,291 €/QALY). Erlotinib maintenance showed a favourable ICER in patients with PS = 0 (94,908 €/QALY), in patients with adenocarcinoma (97,160 €/QALY) and in patient with objective response to induction (101,186 €/QALY), but it is not cost-effective in patients with PS =1, in patients with non-adenocarcinoma or with stable disease after induction chemotherapy.Conclusion: Gemcitabine-or erlotinib-maintenance therapy had ICERs that varied as a function of histology, PS and response to first-line chemotherapy