Primary and acquired platinum-resistance among women with high grade serous ovarian cancer

Slaughter, K.N.; Holman, Laura L.; Thomas, E. L.; Gunderson, Camille C.; Lauer, Jacob K.; Ding, Kai; McMeekin, D. Scott; Moore, Kathleen

doi:10.1016/j.ygyno.2016.05.020

Cited by 29 publications

(26 citation statements)

References 15 publications

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“…This is in stark contrast to patients with platinum-sensitive recurrences, who can expect response rates of 30% to 90% to additional platinum agents. In a recent study comparing survival outcomes in the resistance setting, Slaughter et al 24 reported that patients with acquired platinum resistance had a median overall survival from the date of platinum resistance of 21.9 months, which was not statistically different from that in patients with primary platinum-resistant disease.…”

Section: Discussionmentioning

confidence: 99%

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

Moore

Martin

O’Malley

et al. 2017

JCO

176

109

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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 (FRa) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRa-positive and platinum-resistant ovarian cancer. Patients and MethodsPatients 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 FRa 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. ResultsForty-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. ConclusionIMGN853 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.

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Section: Discussionmentioning

confidence: 99%

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

Moore

Martin

O’Malley

et al. 2017

JCO

176

109

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“…In our study, we found that both high quantitative vimentin expression and a high intensity of vimentin expression in cancer cells were associated with a better prognosis. This may be explained by the role of vimentin in the regulation of cancer cell platinum-resistance, as this is one of the most important factors influencing patient prognosis [27]. In their study, Huo et al used two pairs of ovarian cancer cell lines [21].…”

Section: Discussionmentioning

confidence: 99%

High tumor cell vimentin expression indicatesprolonged survival in patients with ovarian malignant tumors

et al. 2019

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“…Many clinical trials, including the ICON1 and ACTION trials demonstrated that the survival of ovarian cancer patients improves when adjuvant chemotherapy is added to the surgical procedure; thus, chemotherapy resistance would undoubtedly lead to shorter survival times [ 21 , 22 ]. Although HGSC is more sensitive to chemotherapy, compared to other histotypes such as clear cell and mucinous carcinoma, appoximately 25% of patients experience primary platinum-resistance [ 23 , 24 ]. In our cohort, the platinum-resistance rate was 25.8%, and low Ki67 expression was more common in platinum-resistant patients (86.1%).…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of Ki67 in ovarian high-grade serous carcinoma: an 11-year cohort study of Chinese patients

et al. 2016

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ObjectiveThis study sought to assess the prognostic role of Ki67 in primary ovarian high-grade serous carcinoma (HGSC) and to determine whether Ki67 expression can predict responsiveness to platinum and paclitaxel chemotherapy.ResultsA total of 318 women were included in the analysis and the median follow-up time was 48 months (range, 3–150 months). Ki67 proliferation indices ranged from 3% to 95% with a median of 40%. Using 40% as the cut-off value for the Ki67 index, we classified 141 patients as having low Ki67 expression and 177 patients as having high Ki67 expression. Low Ki67 expression was a predictor of platinum resistance (hazard ratio (HR) 2.85, 95% CI 1.43–5.98, P < 0.001). In the Kaplan-Meier analysis, comparisons of patients with low versus high Ki67 expression demonstrated that low Ki67 expression was significantly associated with decreased progression-free survival (PFS) (22% vs. 34% for 5-year PFS, P < 0.001) and decreased overall survival (OS) (31% vs. 55%, P < 0.001). Multivariate analysis indicated that low Ki67 expression was associated with decreased PFS (HR 2.98, 95% CI 1.75–6.56, P < 0.001) and decreased OS (HR 1.74, 95% CI 1.38–5.01, P = 0.003).Materials and MethodsA retrospective study of patients with stage I-IV primary ovarian HGSC was conducted from January 1, 2002, to December 31, 2012. Ki67 levels were measured via immunohistochemistry (IHC) and analyzed with respect to clinicopathological factors, and a survival analysis was performed.ConclusionsHGSC appears to be a heterogeneous disease with different clinical outcomes. Low Ki67 expression (< 40%) in HGSC is significantly associated with platinum resistance and decreased survival.

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Primary and acquired platinum-resistance among women with high grade serous ovarian cancer

Cited by 29 publications

References 15 publications

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

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

High tumor cell vimentin expression indicatesprolonged survival in patients with ovarian malignant tumors

The prognostic value of Ki67 in ovarian high-grade serous carcinoma: an 11-year cohort study of Chinese patients

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