6 research outputs found
Nouvelles AMMs au niveau europĂ©en : alpĂ©lisib â cancer du sein RH+/HER2â mĂ©tastatique avec mutation PIK3CA
International audienc
Clinical efficacy of the optimal biological dose in early-phase trials of anti-cancer targeted therapies
Impact of Liver Metastases and Number of Metastatic Sites on Immune-Checkpoint Inhibitors Efficacy in Patients with Different Solid Tumors: A Retrospective Study
Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS number on progression-free survival (PFS) and overall survival (OS) in a large single-arm retrospective multicentric cohort (IMMUCARE) of patients treated with anti-PD(L)-1 for different solid tumors. Results: A total of 759 patients were enrolled from January 2012 to October 2018. The primary tumor types were non-small cell lung cancer (71%), melanoma (19%), or urologic cancer (10%). At the time of ICI initiation, 167 patients (22%) had LM and 370 patients (49%) had more than MS. LM was associated with a shorter median PFS of 1.9 months (95% CI: 1.8â2.5) vs. 4.0 months (95% CI: 3.6â5.4) in patients without LM (p p < 0.001). Interestingly, LM were not associated with shorter PFS, or OS compared to other MS types (brain, bone, or lung) in patients with only one MS. Patients with multiple MS also had poor clinical outcomes compared to patients with only one MS. The presence of LM and MS number were independent prognostic factors on overall survival. Conclusion: The presence of LM or multiple MS were associated with poorer survival outcomes in patients treated with anti-PD(L)-1
The Increasing Prognostic and Predictive Roles of the Tumor Primary Chemosensitivity Assessed by CA-125 Elimination Rate Constant K (KELIM) in Ovarian Cancer:A Narrative Review
SIMPLE SUMMARY: In patients with advanced ovarian cancers, the standard first-line treatment includes debulking surgery and platinum-based chemotherapy, followed by a maintenance treatment. Contrary to the completeness of the debulking surgery, the prognostic impact of the tumor chemosensitivity in the success of the first-line treatment has been insufficiently addressed due to the lack of a reliable indicator of the primary chemosensitivity, as acknowledged by European consensus conferences. The objective of this narrative review is to present an overview of the modeled CA-125 ELIMination rate constant K (KELIM) calculation based on the longitudinal CA-125 kinetics during the first chemotherapy cycles and its utility as an early marker of tumor primary chemosensitivity. Easily calculable online, KELIM was shown to be a consistent and reproducible early prognostic marker that could be useful for understanding the prognosis of patients and adjusting the medicalâsurgical treatments. ABSTRACT: Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate because 75% of patients are diagnosed with advanced stage IIIâIV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery (IDS). In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent IDS. Across seven studies with more than 12,000 patients, including six large randomized clinical trials and a national cancer registry, along with a mega-analysis database with 5842 patients, the modeled CA-125 ELIMination rate constant K (KELIM), the calculation of which is based on the longitudinal kinetics during the first three cycles of platinum-based chemotherapy, was shown to be a reproducible indicator of tumor intrinsic chemosensitivity. Indeed, KELIM is strongly associated with the likelihood of complete IDS, subsequent platinum-free interval, progression-free survival, and overall survival, along with the efficacy of maintenance treatment with bevacizumab or veliparib. As a consequence, KELIM might be used to guide more subtly the medical and surgical treatments in a first-line setting. Moreover, it could be used to identify the patients with poorly chemosensitive disease, who will be the best candidates for innovative treatments meant to reverse the chemoresistance, such as cell cycle inhibitors or immunotherapy
Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis
Background
In patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors.
Methods:
The dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (â„1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model.
Results:
KELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41â0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45â0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, âŒ45.0, and 22.1 months) and PFS (58.1, âŒ15.0, and 8.0 months). Surrogacy for OS and for PFS was not established.
Conclusion:
KELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success
Progression-free survival on endocrine therapy, before or after chemotherapy, in hormone receptor-positive HER2-negative metastatic breast cancer
PURPOSE: A major question when treating HR+/HER2- metastatic breast cancer (MBC) is whether early introduction of chemotherapy (CT) increases endocrine resistance. We aimed to describe progression-free survival (PFS) under first endocrine therapy (ET) depending on whether given before or after CT in a large nationwide cohort, in the pre-CDK era. METHODS: The real-life retrospective ESME database includes all patients with MBC whose first-line treatment was initiated between 2008 and 2014 in one of the 18 French Comprehensive Cancer Centres. Our primary objective was to compare PFS from start of first ET in patients with HR+/HER2- MBC who received ET or CT first. RESULTS: We identified 6293 patients who received at least one ET line during their first two therapeutic lines for MBC. As first-line therapy, 3832 (60.9%) received ET alone (ET1 1st group), whilst 2461 (39.1%) received CT, including 2024 patients (32.2%) with maintenance ET after CT (ET1 after CT group). Median PFS under first ET was 12.4Â months (95% CI 11.9-13.1) in ET 1st group vs. 12.6Â months in ET1 after CT group (95% CI 12.1-13.4), HR 0.96 (95% CI 0.90-1.01, Pâ=â0.1277). CONCLUSIONS: PFS under first ET appears identical whether prescribed before or after chemotherapy. These data suggest chemotherapy does not promote endocrine resistance