scholarly journals Adipose tissue area as a predictor for the efficacy of apatinib in platinum-resistant ovarian cancer: an exploratory imaging biomarker analysis of the AEROC trial

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Xin Huang ◽  
Chuanbo Xie ◽  
Jie Tang ◽  
Wenzhuo He ◽  
Fan Yang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Ovarian Cancer ◽  
Adipose Tissue ◽  
Response Rate ◽  
Objective Response ◽  
Oral Etoposide ◽  
Computed Tomography Scan ◽  
Platinum Resistant ◽  
Platinum Refractory ◽  
Tomography Scan

Abstract Background Vascular endothelial growth factor (VEGF)-targeted therapy is effective in patients with ovarian cancer. Whether adipose tissue (AT) could predict the efficacy of VEGF receptor (VEGFR) inhibitors in ovarian cancer is unknown. We aimed to evaluate the ability of distinct AT depots to predict the efficacy of apatinib, a VEGFR inhibitor, in recurrent ovarian cancers included in the AEROC trial. Methods The AEROC was a single-arm phase 2 trial of apatinib and oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer. Apatinib was administered continuously, and oral etoposide was administered every 21 days for a maximum of six cycles. This was a post hoc study based on the AEROC trial. Areas of visceral AT (VAT), subcutaneous AT (SAT), and intermuscular AT (IMAT) were measured using computed tomography scan at baseline to assess their association with the objective response rate, progression-free survival, and overall survival. Results Of the 35 treated patients, 31 patients with at least one post-baseline efficacy assessment by computed tomography scan were included in this study. After adjusting for apatinib exposure, high VAT (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.03–0.90, P = 0.037) and SAT (OR, 0.16; 95% CI, 0.03–0.87, P = 0.034) were significantly associated with a higher objective response rate. Further, decreased risks of disease progression and death were associated with high VAT (hazard ratio [HR], 0.39; 95% CI, 0.17–0.92, P = 0.031, and HR, 0.12; 95% CI, 0.04–0.40, P < 0.001, respectively), SAT (HR, 0.35; 95% CI, 0.15–0.83, P = 0.027, and HR, 0.24; 95% CI, 0.08–0.67, P = 0.007, respectively), and IMAT (HR, 0.20; 95% CI, 0.06–0.74, P = 0.016, and HR, 0.13; 95% CI, 0.03–0.62, P = 0.011, respectively). Conclusions High areas of VAT, SAT, and IMAT were significantly associated with better outcomes in patients with platinum-resistant or platinum-refractory ovarian cancer who received VEGFR inhibitors. AT assessments may be valuable as patient-specific imaging biomarkers for predicting response to VEGFR inhibitors. Trial registration ClinicalTrials.gov identifier: NCT02867956.

scholarly journals Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha–Targeting Antibody–Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study

2017 ◽  
Vol 35 (10) ◽  
pp. 1112-1118 ◽  
Author(s):  
Kathleen N. Moore ◽  
Lainie P. Martin ◽  
David M. O’Malley ◽  
Ursula A. Matulonis ◽  
Jason A. Konner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Folate Receptor ◽  
Objective Response ◽  
Antibody Drug Conjugate ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant ◽  
Duration Of Response ◽  
Antibody Drug

Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate consisting of a humanized anti–folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.

Uplift (ENGOT-ov67): A pivotal cohort to evaluate XMT-1536 (upifitamab rilsodotin), a NaPi2b-directed antibody drug conjugate for platinum-resistant ovarian cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5607-TPS5607
Author(s):  
Debra L. Richardson ◽  
Erika P. Hamilton ◽  
Ana Oaknin ◽  
Leslie M. Randall ◽  
Susana N. Banerjee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Primary Objective ◽  
Antibody Drug Conjugate ◽  
Regulatory Review ◽  
Platinum Resistant

TPS5607 Background: XMT-1536 (upifitamab rilsodotin), is a first-in-class Dolaflexin ADC targeting NaPi2b, a sodium-dependent phosphate transport protein, broadly expressed in solid tumors such as serous epithelial ovarian cancer (OC) and non-small cell lung adenocarcinoma. XMT-1536 uses the Dolaflexin platform to deliver approximately 10 DolaLock auristatin payload molecules per antibody and is being evaluated in a Phase I study (NCT03319628). Observation of preliminary antitumor activity was reported in the ovarian cancer expansion cohort, including in patients previously treated with bevacizumab and PARPi (Tolcher et al, ASCO 2019; Richardson et al, ASCO 2019; Hamilton et al, ESMO 2020). Updated data on the OC cohort included 31 patients with higher NaPi2b expression as of December 2020 (Mersana Therapeutics, 2021). In these patients, the ORR was 32% and the DCR was 74%. Complete responses were observed in 2 patients with platinum-resistant ovarian cancer, both of whom had received prior treatment with bevacizumab and PARP inhibitors. Platinum resistant ovarian cancer remains a serious unmet medical need as treatment options are limited and response rates to these treatments are low. Based on the favorable safety and efficacy profile of XMT-1536, UPLIFT was designed as a Phase 2 single-arm registrational cohort of patients with platinum resistant ovarian cancer as part of the ongoing Phase I FIH dose escalation and expansion study to accelerate development and provide a streamlined pathway to regulatory review. Methods: The UPLIFT cohort is enrolling patients with platinum resistant high grade serous ovarian, fallopian tube and primary peritoneal cancer with up to 4 prior lines of therapy. The RP2D of XMT-1536 was determined to be 43 mg/m2 administered intravenously every 4 weeks (q4w) and will be the dose evaluated in the UPLIFT cohort. UPLIFT will enroll approximately 180 patients with platinum-resistant advanced ovarian cancer to obtain approximately 100 patients with higher NaPi2b expression. Prior bevacizumab is required for those patients with 1 or 2 prior lines of therapy. Tumor samples (fresh or archived) will be collected prior to enrollment for retrospective tumor tissue evaluation of NaPi2b expression. The primary objective is assessment of confirmed objective response rate to XMT-1536 as assessed by Investigator in patients with higher NaPi2b expression. Secondary endpoints include confirmed objective response rate regardless of NaPi2b expression, duration of response, and adverse events. Correlative aims include assessing blood and tissue biomarkers for association with clinical benefit. This study is being conducted in collaboration with ENGOT and GOG. Patients will be enrolled globally. Clinical trial information: NCT03319628.

scholarly journals Inguinal bladder hernia with lipomatosis of the bladder wall: A potential clinical pitfall for cancer

2019 ◽  
Vol 86 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Alessia Cimadamore ◽  
Erika Palagonia ◽  
Paola Piccinni ◽  
Marco Misericordia ◽  
Andrea Benedetto Galosi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Adipose Tissue ◽  
Inguinal Hernia ◽  
Urinary Bladder ◽  
Bladder Wall ◽  
Muscularis Propria ◽  
Computed Tomography Scan ◽  
Bladder Hernia ◽  
Tomography Scan ◽  
Normal Urothelium

A 70-year-old man was referred to the Urology Service of our University Hospital for an irregular thickening of the left anterior–lateral urinary bladder wall found in a computed tomography scan following gross haematuria. In particular, the computed tomography scan showed irregularity of the mucosal aspect and an irregular thickening of the bladder wall in close proximity of an inguinal hernia. The computed tomography exam also showed an unusual little fatty seizure in the parietal planes. A magnetic resonance imaging confirmed the thickening in the same area as the hernia with a mainly extraluminal presentation and extension in the perivesical adipose tissue. Cystoscopy did not show alteration of the mucosal surface. Urine cytology showed normal urothelium cells. At the time of the left inguinal hernia repair, the bladder was isolated from the inguinal hernia fat tissue and then opened with median cystotomy. Biopsy of the anterior–lateral bladder wall showed normal urothelium and an abundant component of mature lobules of adipose tissue in the sub-epithelial connective tissue extending among the muscle bundles of muscularis propria, compatible with a diagnosis of lipomatosis, a very rare lesion in the urinary bladder.

Oral etoposide is active against platinum-resistant epithelial ovarian cancer.

1994 ◽  
Vol 12 (1) ◽  
pp. 60-63 ◽  
Author(s):  
P J Hoskins ◽  
K D Swenerton
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Epithelial Ovarian Cancer ◽  
Surface Area ◽  
Body Surface ◽  
Response Rate ◽  
The Other ◽  
Fixed Dose ◽  
Oral Etoposide ◽  
Platinum Resistant

PURPOSE To determine whether etoposide (VP16) is more effective when administered on a chronic schedule, women with clinically defined platinum-resistant epithelial ovarian cancer (EOC) were studied. PATIENTS AND METHODS Thirty-one eligible women were treated with oral VP16. The first seven received a dose that varied depending on their body-surface area, but this proved too toxic, and so a fixed dose of 100 mg orally per day for 14 days every 3 weeks was used for the other subjects. RESULTS The response rate was 26% (95% confidence interval [CI], 11% to 41%). The 28 women with cancer that had progressed while they were receiving a platinum analog had a response rate of 21% (95% CI, 6% to 36%). Response durations were short. CONCLUSION When administered on this chronic schedule, VP16 has activity against platinum-resistant EOC.

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