This study established a trabectedin dose of 0.8 mg/m(2) combined with carboplatin AUC 4 and given every 4 weeks as the most feasible schedule in carboplatin-pretreated patients. Dose and cycle recommendations for carboplatin-naïve patients warrant further evaluation.
Backgroud: Tumor-derived circulating cell-free DNA (cfDNA) is a dynamic source for determination of tumor mutation status. We have previously demonstrated the prognostic value of BRAFV600 mutation status in pretreatment cfDNA (BRAF pre-cfDNA) in advanced melanoma patients (p) treated with BRAF inhibitors (median overall survival [OS] 7 months [m] vs 22m for BRAF pre-cfDNA positive and negative p, respectively p = 0.017)1. Based on these results, the Spanish Melanoma Group conducted a prospective study in 13 centers to determine the prognostic value of BRAFV600 mutation in pre-cfDNA, the change in mutation status at time of first evaluation (BRAF early-cfDNA), and the correlation of BRAF cfDNA dynamics with clinical evolution (GEM1304) (ClinicalTrials.gov Identifier: NCT01960634). Methods: One hundred and fifty nine plasma and serum samples from 66 stage IV BRAF mutant melanoma p were collected before and during treatment, until disease progression. A quantitative 5’-nuclease PCR based assay was used to determine BRAFV600 mutation status in cfDNA. Results: Most p were stage M1c (62%), treated with BRAF inhibitors (53%), and not previously treated (67%). BRAF pre-cfDNA was positive in 42 p (64%). Median OS was 6.4 m (95% CI: 10.9-23.6) and 17 m (95% CI: 3.5-9.2) for p with positive and negative BRAF pre-cfDNA, respectively (p = 0.06). Significant differences in OS were observed according to BRAF early-cfDNA negativization: 4.7 m (95%CI: 1.2-8.1) in those with persistence of BRAF in cfDNA (12 p), not reached (NR) in p with BRAF early-cfDNA negativization (11 p), and 22 m (95%CI:0.6-43.9) in those who continued to be negative (17 p) (p<0.001). Median progression free survival (PFS) was 3.4 m (95% CI: 2.1-4.6), 16.8 m (95% CI: 6.9-26.8) and 15.3 (95%CI: 1.1-29.6), respectively (p<0.001). There were also significant differences according to BRAF early-cfDNA among p treated with BRAF inhibitors: in p with persistence of BRAF in cfDNA (8p), median OS was 4.7 m (95% CI:16-7.8), NR for those with BRAF early-cfDNA negativization (9p), and 22 m (95%CI: 7.9-36.6) for those who continued to be negative (8 p) (p<0.001). Median PFS was 3.6 m (95% CI: 2.2-5.1), 16.9 m (95% CI: 6.9-26.9) and 18 m (95% CI: 0.6-35.3), respectively (p = 0.001). In those p with serial samples taken during treatment, BRAF mutation disappeared from cfDNA in all cases who responded (18). Those with persistence of mutation during follow up had rapid progression and death (10). BRAF mutation had relapsed in cfDNA at time of progression in 6/15 cases. Conclusions: Patients with early negativization of BRAFV600 in cfDNA have excellent prognosis, at least as good as those with negative BRAF in pre-cfDNA. González-Cao et al. Mel Res 2015; 25:486 Citation Format: Maria Gonzalez Cao, Jose Luis Manzano, Virtudes Soriano, Teresa Puertolas, Ainara Soria, Clara Mayo, Margarita Magem, Miguel Angel Molina, Clara Montagut, Eva Muñoz, Delvys Rodriguez, Elizabeth Perez, Almudena Garcia, Javier Cortes, Nuria Jordana, Jordi Rodon, Niki Karachaliou, Rafael Rosell. BRAF mutation analysis in cell free tumoral DNA (cfDNA) of melanoma patients: results from the prospective study GEM1304 (Spanish Melanoma Group). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 468.
8084 Background: Lung cancer is the leading cause of cancer mortality among women in many countries. Gender differences have been reported, most of them based on retrospective analysis. Methods: WORLD07 is a prospective, multicenter, epidemiologic female-specific lung cancer database developed by the Spanish Lung Cancer Group. Data on demographics, previous cancer history, reproductive and hormonal status, diet, alcohol, tobacco, and occupational information are being collected just as histology, stage, treatment and survival. Results: From October 2007 to Nov 2008, 342 female newly diagnosed of lung cancer were collected in an e-database in 20 Spanish centers. Patients (p) characteristics are: median age 61.7 years (y) (range: 36 - 87); Caucasian: 98.2%; Marital status (%): married 67.7, unmarried 11.2, divorced 7.1, widow 14. Educational level (%): basic 57.4, secondary 29.1, university 13.5. Median age of menarche 12.7 y. Children: 79.4% (median: 2); Median age of first child 27 y. Oral contraceptive: 30.6%. Pre-menopausal 15.4%,postmenopausal 84.6%. Median age of menopause 46.7 y. HRT: 5.3%. Median duration of HRT: 4.4 y. Obesity: 11.3%. Smoking habit (%): never (passive smoker/no exposition)/former/current smokers: 42 (42.8/57.2) /19 /39; Median packs/year 72.4. Former smokers: 1–5/5–10/10–15/>15 y (%): 51/11.8/7.8/29.4. Work exposure 3.5%. Alcohol consumption 3.2%. Familial history of cancer: 45.5% (lung cancer 29.7%). Previous history of cancer 13.8% (breast 33.3%). Current lung cancer histology (%): adenocarcinoma/BAC/squamous/large cell/NOS: 70.4/5.7/10.4/7.9/5.7. SCLC 11.8%. TNM I/II/III/IV (%): 16/3.9/28.7/51.4. Surgical treatment 24.7 % (lobectomy/pneumonectomy/exploratory: 85.5/9.2/5.3%). Available data of 122 stage IV NSCLC p: 74.6% receive chemotherapy, 92.3% of them two drugs and 68.9 % platinum-based (59% cisplatin). EGFR mutations analysis 7.9%. Conclusions: According this series, 42% of Spanish lung cancer women are never smokers and 70.4% have adenocarcinoma. Other collected information, choice of treatment and survival outcomes will be also analyzed. No significant financial relationships to disclose.
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