Supervised Physical Activity Quickly Improves Social Dimension of Quality of Life in Breast Cancer Patients

PurposeThe objectives of the present study was to evaluate the implementation of the program in real life and the evolution of the quality of life (QoL) in breast cancer patients after 3 months of supervised PA in real life and to determine the factors associated with changes in various QoL dimensions.MethodsThis prospective cohort study was carried out in female patients with breast cancer diagnosed within a maximum of 3 yr. QoL and physical exertion intensity during the supervised physical activity (PA) sessions were assessed by the Quality of Life Questionnaire for Cancer and Borg scale, respectively. Statistical analyses comparing QoL scores between the start and the end of supervised PA program were assessed using paired Student's t-tests. Multivariate analysis was performed by linear regression with only variables with a P value ResultsA total of 93 patients were included in the analyses. There was a significant improvement of social functioning at T3 ( increment = 11.5; P < 0.001). The improvement of social functioning was significantly and independently associated with the Borg improvement (beta = 2.66 +/- 1.31, P = 0.046), chemotherapy (beta = 11.03 +/- 5.45, P = 0.046), hormone therapy (beta = -13.91 +/- 5.51, P = 0.013), social isolation (beta = -14.81 +/- 6.55, P = 0.026), and comorbidities (beta = -15.32 +/- 5.59, P = 0.007).ConclusionsWe observed a real enthusiasm and need among patients for practicing PA supervised by a sport trainer near their home. The increase in the intensity of exercise over time contributes to the improvement of the QoL, especially on the social functioning. These results, consistent with previous literature, reinforce the importance of exercise intensity on many dimensions of QoL. In addition, patients expressed great satisfaction with the supervised program, resulting in a strong desire to maintain long-term PA

Circulating tumor DNA strongly predicts efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced gastro-esophageal adenocarcinoma

International audienceEfficacy of 2nd line treatment in advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma remains limited with no identified strong predictor of treatment efficacy. We evaluated the prognostic value of circulating tumor DNA (ctDNA) in predicting the efficacy of immune checkpoint inhibitors (ICI) plus chemotherapy in the randomized PRODIGE 59-FFCD 1707-DURIGAST trial

FOLFIRI Plus Durvalumab with or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: The PRODIGE 59-FFCD 1707-DURIGAST Randomized Clinical Trial

International audience© 2024 American Medical Association. All rights reserved.Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, Setting, and Participants: The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention: Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and Measures: The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results: Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS &lt;5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS &lt;1%). Conclusions and Relevance: Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03959293

Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Primary Breast Cancer

PURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor–resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PATIENTS AND METHODS In this randomized double-blind phase III study, women with high-risk, hormone receptor–positive, human epidermal growth factor receptor 2–negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov (identifier: NCT01805271 ). RESULTS Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio, 0.95; 95% CI, 0.69 to 1.32; P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P &lt; .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%. CONCLUSION Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting. </jats:sec

Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Primary Breast Cancer

International audiencePURPOSE Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor–resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PATIENTS AND METHODS In this randomized double-blind phase III study, women with high-risk, hormone receptor–positive, human epidermal growth factor receptor 2–negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov identifier: NCT01805271 . RESULTS Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio = 0.95, 95% CI, 0.69 to 1.32, P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P < .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%. CONCLUSION Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting

Abstract PD9-08: Prognostic value of EndoPredict test in patients screened for UNIRAD, a UCBG randomized, double blind, phase III international trial evaluating the addition of everolimus (EVE) to adjuvant hormone therapy (HT) in women with high risk HR+, HER2- early breast cancer (eBC)

Abstract Background: The double blind randomized UNIRAD trial (NCT01805271) showed no evidence that adding Everolimus (EVE) to adjuvant endocrine therapy (EHT) for high-risk early breast cancer (BC) improved 3-year disease-free survival (iDFS) compared with EHT alone. In this trial, high risk was defined by any T and either ≥4N+, or ≥1N+ after neoadjuvant treatment, or ≥1N+ and EPclin high risk (EPCH) score ≥3.3. This sub analysis is aimed to verify prognostic added value of EndoPredict test results on outcomes in patients screened for the UNIRAD study.. Material and methods: From May 2015 to March 2020, 777 patients were screened with the EndoPredict test. Complete results were obtained for 767 of them. 662 pts were classified as EPCH and 429 were randomized in UNIRAD. 233 pts with EPCH and 105 pts with EPclin low risk (EPCL) were not randomized but followed up for iDFS. Statistical analysis: Kaplan-Meier estimates the association of the integrated molecular-clinico-pathologic EPclin score, and the 12-gene molecular EP score, with iDFS (primary endpoint) and dMFS (secondary endpoint). Independent prognostic added value of EPclin score was tested in a multivariate Cox model after adjusting on tumor characteristics (Grade and T, N). A two-sided p-value less than 0.05 considered as statistically significant, 95% confidence intervals reported with HR. Results: Median follow-up of the cohort was 36.6 mo (0-69) since EndoPredict test. As for the whole population, there was no significant difference in iDFS between treatment arms in the randomized EPCH group. On the other hand, EPclin was an independent prognostic factor for iDFS. 36 mo relapse rate from testing for patients in the EPCL group and the EPCH group was 0% and 7%, respectively (HR supposing continuous EPclin score: 2.36, 95%CI: 1.7-3.3, p &amp;lt; .0001). This difference remained significant when assessed in a cox model with tumor size, number of positive nodes and tumor grade (HR: 1.96, 95%CI: 1.32-2.9, p=0.0008). Furthermore, EPclin results was independently correlated to distant metastatic free survival: 36 mo dMFS for patient in the EPCL and EPCH group was 100% and 94%, respectively (adjusted HR: 2.13, 95%CI:11.3-3.4, p = .0014). Of interest when assessing prognostic of patients within quartiles of EPclin Score (&amp;lt;3.6; 3.6-4.1; ≥4.1-4.8; ≥ 4.8), 36 mo iDFS was 99%; 95%; 94% and 86%, respectively. Conclusion: These prospective results confirm the significance of EPclin score as an independent prognostic parameter in node positive ER+/HER2- eBC patients receiving standard adjuvant treatment. This information can be of importance for selection of specific adjuvant intervention, particularly chemotherapy and new targeted therapy. Further analysis on the EP score will be presented at the meeting. Citation Format: Frederique Penault-Llorca, Florence Dalenc, Sylvie Chabaud, Paul Cottu, Djelila Allouache, David Cameron, Jean-Philippe Jacquin, Julien Grenier, Laurence Venat Bouvet, Apurna Jegannathen, Mario Campone, Francesco Del Piano, Marc Debled, Anne-Claire Hardy-Bessard, Sylvie Giacchetti, Philippe Barthelemy, Laure Kaluzinski, Audrey Mailliez, Marie-Ange Mouret-Reynier, Eric Legouffe, Anne Cayre, Mathilde Martinez, Catherine Delbaldo, Delphine Mollon-Grange, E. Jane Macaskill, Matthew Sephton, Laëtitia Stefani, Blaha Belgadi, Matthew Winter, Hubert Orfeuvre, Magali Lacroix-Triki, Herve Bonnefoi, Judith Bliss, Jean-Luc Canon, Jerome Lemonnier, Fabrice Andre, Thomas Bachelot. Prognostic value of EndoPredict test in patients screened for UNIRAD, a UCBG randomized, double blind, phase III international trial evaluating the addition of everolimus (EVE) to adjuvant hormone therapy (HT) in women with high risk HR+, HER2- early breast cancer (eBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-08.</jats:p