GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

International audienceGenetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors

Geriatric Assessment Implementation before Chemotherapy in MEtastatic Prostate Cancer, Results from the Real-Life Study GAMERS

Geriatric assessment (GA) can predict and improve treatment tolerance and estimate overall survival in older patients with cancer. Several international organizations promote GA; however, data related to its implementation in daily clinical practice are still limited. We aimed to describe GA implementation in patients over 75 years old with metastatic prostate cancer treated with docetaxel as first-line treatment, and with positive G8 screening test or frailty criteria. This retrospective real-world study included 224 patients treated from 2014 to 2021 in four French centers, including 131 patients with a theoretical indication of GA. Among the latter, 51 (38.9%) patients had GA. The main barriers to GA were the lack of systematic screening (32/80, 40.0%), unavailability of geriatric physician (20/80, 25.0%), and absence of referral despite a positive screening test (12/80, 15.0%). With GA performed in only one-third of the patients with a theoretical indication in daily clinical practice, mostly due to an absence of screening test, the use of GA is currently sub-optimal

What is the place of clinical variables in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy ?

International audienceBackground: Chemotherapy (CT) has shown its effectiveness in symptom control and quality of life improvement in advanced NSCLC patients. The therapeutic strategy and some clinical variables could have a major impact on outcome. Methods: Our retrospective analysis evaluated the impact on overall survival (OS) of the clinical benefit (CB), ECOG performance status (PS) and toxicity, function of treatment. CB was defined as disease-related symptoms improvement according to hospitalization report. Only grade III-IV CTC-NCI version 2 toxicities have been considered. OS was calculated between start of CT and death or last follow-up. Multivariate Cox regression analysis including CB, PS, toxicity and age, stratified by AJCC initial stage was used. Results: Data of 68 consecutive stage IIIB-IV patients treated in a single French centre were analyzed. Chemotherapy was platinum-salt based in 88, 45 and 25% of pts for the first, second and third-line, respectively. Median age was 61 years, 37% were women. More than half (66%) were metastatic and 14% were previously irradiated. Median survival was 14 months (95% CI, 6.1-21.8), 53 % of patients are dead. The risk of death PS-related was multiplied by 2.3, 2.4 and 5.3 for the first, second and third-line of CT, respectively. PS and CB were initially associated with OS (first and second-line CT), but after the third-line of CT only PS was significantly related with OS. The risk of death reduction induced by a CB was 59, 82 and 29%, respectively. Less toxicities during CT were associated with a better OS (an unsignificant 20- 30% risk of death reduction), independently of the chronology of CT. Older pts >70 years have a higher risk of death (HR=1.87), independently of the CB and treatment-related toxicities in the multivariate analysis (P=0.18), sex-adjusted. Conclusions: No matter how many lines of CT are used for a specified patient, the ECOG PS was a patient-related variable with a dominant impact on the outcome. CT must be less toxic in order to achieve a CB and ameliorate the PS

Management of gastric neuro-endocrine tumours in a large French national cohort (GTE).

IF 3.131International audienceINTRODUCTION:Gastric neuro-endocrine tumours are rare. European guidelines for the management of neuro-endocrine tumours have been published in 2012. The aim of our survey was to study the management of gastric neuro-endocrine tumours registered in the national cohort. A prospective national cohort registers the Neuro-endocrine tumours in France since January 2003 (GTE network). We reviewed all the individual medical reports of gastric neuro-endocrine tumours in order to collect data on treatment.RESULTS:One hundred and ninety seven gastric neuro-endocrine tumours diagnosed between 1964 and 2013 in 20 centres were registered. For 181 cases data were considered complete for our survey. Eighty four tumours were type 1 (46.4%); five types 2 (2.8%); 52 types 3 (28.7%) and 40 types 4 (22.1%). Types 1 and 2 were first endoscopically managed in 93 and 60% of cases, respectively, whereas surgery was first done in 45 and 42%, respectively, of types 3 and 4. Systemic treatment, chemotherapy and/or somatostatin analogue, was first administered exclusively for types 3 and 4. Near 3% of types 1 and 40% of types 2 received at a time somatostatin analogue treatment. Five-year survival rates were 98.3, 100, 63.2 and 31.8% for types 1, 2, 3 and 4, respectively.CONCLUSION:The great majority of gastric neuro-endocrine tumours registered in this national cohort are treated in accordance with the current guidelines. The survival rates we reported must be interpreted with caution, because this cohort registered preferentially selected patients eligible for treatment. The registration of all the gastric neuro-endocrine tumours, in particular type 1 considered as benign and type 4 not eligible for specific anti-cancer treatment must be encouraged

Clinical benefits of non-taxane chemotherapies in unselected patients with symptomatic metastatic castration-resistant prostate cancer after docetaxel: the GETUG-P02 study

International audienceOBJECTIVE:To evaluate the overall benefits of non-taxane chemotherapies in a non-selected population including unfit patients presenting with symptoms and pain.PATIENTS AND METHODS:This randomized phase II study reports data from 92 patients (52% >70 years old; 40% with a performance score of 2) previously treated with taxane-based chemotherapy, collected from 15 centres in France. Patients received i.v. mitoxantrone (MTX), oral vinorelbine, or oral etoposide, together with oral prednisone. Palliative benefit (pain response without progression of the disease), biological and tumoural responses, and toxicity profile as well as geriatric assessment (in elderly population) were analysed on an intention-to-treat basis.RESULTS:The palliative response rate was 17% for the whole population, and reached 29% when considering the MTX arm. Pain control was achieved in 40% of the patients. The median overall survival was 10.4 months, and was longer in palliative responders. Few grade 3-4 toxicities were observed. The subgroup analysis of elderly patients showed similar results regarding the number and dose intensity of treatments, efficacy and safety.CONCLUSION:In a population including frail and/or elderly patients, who are poorly represented in most clinical studies, non-taxane chemotherapy may remain a relevant option for metastatic prostate cancer having relapsed after a docetaxel-based regimen. Although new treatment options are now approved, the decision-making process should take into account their expected benefit/risk ratio based on the patient status

Perioperative Cetuximab with Cisplatin and 5-Fluorouracil in Esogastric Adenocarcinoma: A Phase II Study

Purpose: While perioperative chemotherapy provides a survival benefit over surgery alone in gastric and gastroesophageal junction (G/GEJ) adenocarcinomas, the results need to be improved. This study aimed to evaluate the efficacy and safety of perioperative cetuximab combined with 5-fluorouracil and cisplatin. Patients and Methods: Patients received six cycles of cetuximab, cisplatin, and simplified LV5FU2 before and after surgery. The primary objective was a combined evaluation of the tumor objective response (TOR), assessed by computed tomography, and the absence of major toxicities resulting in discontinuation of neoadjuvant chemotherapy (NCT) (45% and 90%, respectively). Results: From 2011 to 2013, 65 patients were enrolled. From 64 patients evaluable for the primary endpoint, 19 (29.7%) had a morphological TOR and 61 (95.3%) did not stop NCT prematurely due to major toxicity. Sixty patients (92.3%) underwent resection. Sixteen patients (/56 available, 28.5%) had histological responses (Mandard tumor regression grade ≤3). After a median follow-up of 44.5 months, median disease-free and overall survival were 24.4 [95% CI: 16.4-39.4] and 40.3 months [95% CI: 27.5-NA], respectively. Conclusion: Adding cetuximab to the NCT regimen in operable G/GEJ adenocarcinomas is safe, but did not show enough efficacy in the present study to meet the primary endpoint (NCT01360086)