Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial.

PURPOSE: The incidence of lung cancer has dramatically increased in women. Preclinical data have suggested that combining EGFR-tyrosine kinase inhibitor (TKI) with an antiestrogen may overcome resistance to EGFR-TKI. PATIENTS AND METHODS: The IFCT-1003 LADIE trial was a 2 × 2 arms parallel open-label randomized phase II trial. EGFR-TKI-naïve postmenopausal women with advanced lung cancer were treated with gefitinib (G) versus gefitinib + fulvestrant (G+F) in the EGFR-mutated group (EGFR+) or with erlotinib (E) versus erlotinib + fulvestrant (E+F) in the EGFR wild-type group (EGFR-WT). The primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR-WT and EGFR+ patients. RESULTS: Overall, 204 patients (gefitinib 104 and G+F 100) and 175 patients (erlotinib 87 and E+F 88) were enrolled in the EGFR+ and EGFR-WT cohorts. In the EGFR+ cohort, the primary endpoint was reached, with 58% of the G+F group patients being nonprogressive at 9 months. Adding fulvestrant to gefitinib was not associated with improved PFS (9.9 vs 9.4 months) or overall survival (OS; 22.1 vs 28.6 months). In the EGFR-WT cohort, the primary endpoint was also achieved (33.7% of the patients were nonprogressive at 3 months). Adding fulvestrant to erlotinib was not associated with improved outcome (PFS 1.8 vs 2.0 and OS 10.3 vs 7.3 months). No PFS difference was observed regarding estrogen receptor alpha expression. The tolerance was as expected with no treatment-related death. CONCLUSIONS: Adding fulvestrant to EGFR-TKI is feasible, but not associated with prolonged PFS regardless of EGFR status. The lack of benefits while combining fulvestrant to EGFR-TKI does not support its future development in an unselected population.

Overall survival with crizotinib and next-generation ALK inhibitors in ALK-positive non-small-cell lung cancer (IFCT-1302 CLINALK): a French nationwide cohort retrospective study.

Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK-positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK-positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes.ALK-positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib.At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months.Unselected ALK-positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

Lung cancer in elderly patients: a retrospective analysis of practice in a single institution.

UNLABELLED: Incidence of non-small cell lung cancer is increasing especially among elderly with about 40% arising in patients over 70 years old. Most of these elderly patients are under treated. Seventy-one patients with lung cancer over 70 years old were treated in Institut Paoli-Calmettes from January 2000 until December 2003 (male/female: 57/14). Median age was 75.5 years (70-92). OMS 0-1-2-3=4.2-60.6-25.4-4.2%, respectively. Comorbidities were represented by arterial hypertension, coronaropathy, cardiac failure, thrombo-embolism, respiratory failure, diabetes, vascular cerebral dysfunction, and renal failure. 29.6% of patients were without comorbidity, and 14.1% had at least three comorbidities. The averages of the Charlson comorbidity score and the Age-Charlson comorbidity score were 3.4 and 6.6, respectively. Histological characteristics: epidermoïd/adenocarcinoma/undifferentiated/small cells: 39.4%/26.8%/15.5%/9.9%. Most of them were advanced lung cancer: St IIIB=14 (19.7%) and St IV=37 (52.1%). Forty-six patients received chemotherapy (64.8%) with 40 patients (86.9%) with platin (carboplatin or cisplatin). The median number of treatment cycles was 4.1 (range 1-7). Two patients achieved complete response and 15 had partial response. The response rate was 39.6%. The 1-year survival rate was 48.5% and the estimated median survival time was 11 months (95%; 7-18 months) for all patients. The 1-year survival rate was 75% and 21.6% and the estimated median survival time was 25.9 months (95%; 12.6, ND) and 5.7 months (95%; 4.2-9.6) for stage IIIB and IV, respectively. Toxicities were judged acceptable with 19 hospitalizations after chemotherapy, for 16 patients who represent 34.8% of patients who received chemotherapy. CONCLUSIONS: Chemotherapy is feasible in elderly patients with lung cancer. Patients should be evaluated for chemotherapy based on their performance status and comorbidities especially with geriatric assessment rather than age alone. The chemotherapy with platinum seems to be tolerable and effective.

From randomised clinical trials to clinical practice : a pragmatic cost-effectiveness analysis of Paclitaxel in first-line therapy for advanced ovarian cancer.

INTRODUCTION: Paclitaxel plus cisplatin is considered to be the standard first-line therapy for advanced ovarian cancer. Previous to this study, economic data on this combination resulted from randomised clinical trials (RCTs). Therefore, the objective of this study was to compare the clinical and economic outcomes associated with paclitaxel-cisplatin (PC) and cyclophosphamide-cisplatin (CC) regimens using a pragmatic perspective based on daily clinical practice in a French university hospital. METHOD: A retrospective cost-effectiveness analysis, from the hospital-payer perspective, was carried out as a before-after case study in fifty-nine consecutive women with verified International Federation of Gynaecology and Obstetrics (FIGO) stage II, III or IV ovarian cancer treated between 1995 and 2000. Median overall survival (OS) was used as the primary endpoint. The quality-adjusted time was assessed by the quality-adjusted time without symptoms or toxicity (Q-TWiST) method. Direct medical costs were collected for each patient. Monetary values for French prices in the year 2000 were used and converted to US dollars using an exchange rate of USD 1 = 7 French francs. Several univariate sensitivity analyses were carried out varying unit costs, medical practices and administration of paclitaxel. RESULTS: The incremental cost of the PC regimen was USD 10,716 per patient. OS and quality-adjusted time were improved by 10.8 and 9.3 months with the PC regimen. The cost per life-year gained and per added QALY were USD 11,907 and USD 13,827, respectively. The robustness of the results was confirmed in sensitivity analyses. CONCLUSION: Our study suggests that PC may be a cost-effective regimen for advanced ovarian cancer in a French university hospital setting. We reported higher incremental costs and lower clinical benefits than RCT-based findings, suggesting that RCT-based findings were clearly balanced by our pragmatic approach based on clinical practices. Observational studies can provide complementary and balanced data for decision making.