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1.
Ann Oncol ; 35(5): 414-428, 2024 May.
Article in English | MEDLINE | ID: mdl-38431043

ABSTRACT

BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. MATERIALS AND METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low. CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Endometrial Neoplasms , Immunotherapy , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/therapy , Endometrial Neoplasms/immunology , Immunotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Trials, Phase III as Topic , Progression-Free Survival , Randomized Controlled Trials as Topic , Microsatellite Instability , Neoplasm Metastasis
2.
Ann Oncol ; 30(5): 721-732, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30887020

ABSTRACT

BACKGROUND: Ovarian cancer remains the most deadly gynecologic cancer with the majority of patients relapsing within 3 years of diagnosis. Traditional treatment paradigms linked to platinum sensitivity or resistance are currently being questioned in the setting of new diagnostic methods and treatment options. DESIGN: Authors carried out review of the literature on key topics in treatment of recurrent epithelial ovarian cancer (EOC) when platinum is still an option; including secondary surgical cytoreduction, chemotherapy, novel treatment options, and maintenance therapy. A treatment algorithm is proposed. RESULTS: Molecular characterization of EOC is critical to help guide treatment decisions. The role of secondary cytoreductive surgery is currently being evaluated with results from Gynecologic Oncology Group (GOG) 213 and anticipated results from DESKTOP III clinical trials. Chemotherapy backbone has remained relatively unchanged but utilizing non-platinum-based regimens is under investigation. In addition, maintenance therapy with anti-angiogenic therapy and Poly (ADP-ribose) Polymerase (PARP) inhibitors has emerged as the standard of care. Novel combinations, including immunotherapy and anti-angiogenesis agents, may further change the current landscape. CONCLUSIONS: The treatment of recurrent EOC is rapidly changing. Clinical trial design will need to continue to evolve as many novel therapies move to the upfront setting. Ultimately, the treatment of patients with recurrent EOC must incorporate individual patient and tumor factors.


Subject(s)
Carcinoma, Ovarian Epithelial/therapy , Neoplasm Recurrence, Local/therapy , Organoplatinum Compounds/therapeutic use , Ovarian Neoplasms/therapy , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/pathology , Combined Modality Therapy , Cytoreduction Surgical Procedures/methods , Female , Humans , Immunotherapy/methods , Molecular Targeted Therapy , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology
3.
Gynecol Oncol Rep ; 21: 117-118, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28831417

ABSTRACT

•A case of grade 2 endometrial adenocarcinoma in a young woman desiring fertility-sparing treatment•Successful conservative management of refractory endometrial adenocarcinoma with dual progestin therapy•A brief review of conservative management in endometrial adenocarcinoma.

4.
Ann Oncol ; 28(3): 512-518, 2017 03 01.
Article in English | MEDLINE | ID: mdl-27993796

ABSTRACT

Background: Based upon preclinical synergy in murine models, we carried out a phase I trial to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and biomarkers of response for the combination of BKM120, a PI3K inhibitor, and olaparib, a PARP inhibitor. Patients and methods: Olaparib was administered twice daily (tablet formulation) and BKM120 daily on a 28-day cycle, both orally. A 3 + 3 dose-escalation design was employed with the primary objective of defining the combination MTD, and secondary objectives were to define toxicities, activity, and pharmacokinetic profiles. Eligibility included recurrent breast (BC) or ovarian cancer (OC); dose-expansion cohorts at the MTD were enrolled for each cancer. Results: In total, 69 of 70 patients enrolled received study treatment; one patient never received study treatment because of ineligibility. Twenty-four patients had BC; 46 patients had OC. Thirty-five patients had a germline BRCA mutation (gBRCAm). Two DLTs (grade 3 transaminitis and hyperglycemia) were observed at DL0 (BKM120 60 mg/olaparib and 100 mg b.i.d.). The MTD was determined to be BKM120 50 mg q.d. and olaparib 300 mg b.i.d. (DL8). Additional DLTs included grade 3 depression and transaminitis, occurring early in cycle 2 (DL7). Anticancer activity was observed in BC and OC and in gBRCAm and gBRCA wild-type (gBRCAwt) patients. Conclusions: BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will be needed to further define the efficacy of PI3K/PARP-inhibitor combinations as compared with a PARP inhibitor alone.


Subject(s)
Aminopyridines/administration & dosage , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Morpholines/administration & dosage , Ovarian Neoplasms/drug therapy , Phthalazines/administration & dosage , Piperazines/administration & dosage , Adult , Aged , Aminopyridines/pharmacokinetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Dose-Response Relationship, Drug , Female , Germ-Line Mutation , Humans , Middle Aged , Morpholines/pharmacokinetics , Neoplasm Grading , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Phosphoinositide-3 Kinase Inhibitors , Phthalazines/pharmacokinetics , Piperazines/pharmacokinetics , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerases/genetics
5.
Gynecol Oncol ; 143(3): 596-603, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27742473

ABSTRACT

OBJECTIVES: To longitudinally assess quality of life (QOL) in women undergoing radical trachelectomy for early-stage cervical cancer. METHODS: We prospectively enrolled patients with stage IA1-IB1 cervical cancer prior to undergoing radical trachelectomy to complete validated QOL instruments. These instruments included the General Health-Related QOL (SF-12), Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), MD Anderson Symptom Inventory (MDASI), Female Sexual Functioning Index (FSFI), and Satisfaction with Decision scale (SWD). Instruments were filled out at baseline, postoperatively at 6weeks, 6months, 1year, and annually thereafter for 4years. RESULTS: Thirty-nine patients enrolled in the study, and 32 patients were evaluable. The scores for FSFI-arousal (p=0.0002), lubrication (p<0.0001), orgasm (p=0.006), pain (p=0.01), satisfaction (p=0.03) and total score (p=0.004) showed a significant decline at 6weeks then returned to baseline levels by 6 months. The scores for FACT-Cx functional well-being (p=0.02) and physical well-being (p<0.0001), SF-12 bodily pain (p<0.0001), physical functioning (p<0.0001), role physical (p<0.0001), role emotional (p=0.03), social functioning (p=0.002), and MDASI total (p=0.04) showed significantly worsened symptoms at 6weeks then returned to baseline by 6months. The scores for FACT-Cx emotional well-being showed significant worsening of symptoms that persisted at 6-weeks (p=0.004), 6months (p=0.007), 1year (p=0.001), 2years (p=0.002), and 4 years (p=0.03). There was no difference in SWD. CONCLUSIONS: Several quality of life assessments decline immediately postoperatively after radical trachelectomy, however, return to baseline thereafter. The long-term emotional impact of this surgery highlights a need for perioperative counseling in these patients.


Subject(s)
Activities of Daily Living , Carcinoma/surgery , Pain, Postoperative/epidemiology , Quality of Life , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunctions, Psychological/epidemiology , Trachelectomy/methods , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/pathology , Adenocarcinoma/psychology , Adenocarcinoma/surgery , Adult , Carcinoma/pathology , Carcinoma/psychology , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/psychology , Carcinoma, Adenosquamous/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/psychology , Carcinoma, Squamous Cell/surgery , Female , Humans , Longitudinal Studies , Neoplasm Staging , Patient Satisfaction , Postoperative Complications/epidemiology , Postoperative Complications/psychology , Prospective Studies , Role , Sexual Dysfunction, Physiological/psychology , Sexual Dysfunctions, Psychological/psychology , Social Participation , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/psychology , Young Adult
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