Mirvetuximab soravtansine for platinum-resistant epithelial ovarian cancer.

INTRODUCTION: Mirvetuximab soravtansine (mirvetuximab) is an antibody drug conjugate (ADC) comprised of a humanized folate receptor alpha (FRα)-binding monoclonal antibody attached via a cleavable linker to the cytotoxic maytansinoid molecule, DM4. FRα is expressed in several epithelial cancers, including high grade serous ovarian cancer (HGSOC). Mirvetuximab received accelerated approval by the United States Food and Drug Administration (FDA) in November 2022 based on the results of the SORAYA trial, which tested mirvetuximab for the treatment of patients with recurrent platinum resistant HGSOC with high FRα expression and showed an overall response rate (ORR) of 32.4% and a median duration of response of 6.9 months. Mirvetuximab toxicities included low grade ocular and gastrointestinal toxicities. The National Comprehensive Cancer Network (NCCN) ovarian cancer 2023 guidelines adopted mirvetuximab as 2A, and mirvetuximab combined with bevacizumab as 2B, recommendations. AREAS COVERED: This manuscript will review the preclinical and clinical development of mirvetuximab, the toxicities associated with mirvetuximab and mitigation strategies, and future applications of mirvetuximab. EXPERT OPINION: Mirvetuximab represents the first biomarker-directed therapy with an indication specifically for the treatment of PROC. The efficacy and favorable safety profile support further development of mirvetuximab and mirvetuximab combinations in platinum sensitive and newly diagnosed ovarian cancer.

Outcomes of secondary cytoreductive surgery for patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Most women with advanced epithelial ovarian cancer develop recurrent disease, despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. In observational studies, secondary cytoreductive surgery has been associated with improved survival; however its use is controversial, because there are concerns that the improved outcomes may reflect selection bias rather than the superiority of secondary surgery. OBJECTIVE: To compare the overall survival of women with platinum-sensitive recurrent ovarian cancer treated at National Cancer Institute-designated cancer centers who receive secondary surgery vs chemotherapy. STUDY DESIGN: This retrospective cohort study included women from 6 National Cancer Institute-designated cancer centers diagnosed with platinum-sensitive recurrent ovarian cancer between January 1, 2004, and December 31, 2011. The primary outcome was overall survival. Propensity score matching was used to compare similar women who received secondary surgery vs chemotherapy. Additional analyses examined how these findings may be influenced by the prevalence of unobserved confounders at the time of recurrence. RESULTS: Among 626 women, 146 (23%) received secondary surgery and 480 (77%) received chemotherapy. In adjusted analyses, patients who received secondary surgery were younger (P = 0.001), had earlier-stage disease at diagnosis (P = 0.002), and had longer disease-free intervals (P < 0.001) compared with those receiving chemotherapy. In the propensity score-matched groups (n = 244 patients), the median overall survival was 54 months in patients who received secondary surgery and 33 months in those treated with chemotherapy (P < 0.001). Among patients who received secondary surgery, 102 (70%) achieved optimal secondary cytoreduction. There were no significant differences in complication rates between the 2 groups. In sensitivity analyses, the survival advantage associated with secondary surgery could be explained by the presence of more multifocal recurrences (if 4.3 times more common), ascites (if 2.7 times more common), or carcinomatosis (if 2.1 times more common) among patients who received chemotherapy instead of secondary surgery. CONCLUSION: Patients with platinum-sensitive recurrent ovarian cancer who received secondary surgery had favorable surgical characteristics and were likely to have minimal residual disease following secondary surgery. These patients had a superior median overall survival compared with patients who received chemotherapy, although unmeasured confounders may explain this observed difference.

Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody-Drug Conjugate Mirvetuximab Soravtansine.

PURPOSE: Reversible, low-grade ocular adverse events (AE) are associated with administration of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeted antibody-drug conjugate undergoing phase III clinical evaluation in platinum-resistant ovarian cancer. This study investigated the underlying mechanisms of ocular toxicity and evaluated primary prophylactic use of corticosteroid eye drops in patients receiving mirvetuximab soravtansine. PATIENTS AND METHODS: Target expression in the human eye was determined by IHC. The ocular toxicity profile of mirvetuximab soravtansine was assessed preclinically using Dutch-Belted rabbits. In a phase I clinical study, patients with ovarian cancer were treated with 6 mg/kg mirvetuximab soravtansine intravenously once every 3 weeks, including one expansion cohort with corticosteroid eye drops administered daily for the first 10 days of each treatment cycle. RESULTS: FRα expression was absent from human corneal tissues. Ocular abnormalities in the rabbit eye appeared phenotypically consistent with off-target effects on the cornea. Forty patients were enrolled in the expansion cohort. Reversible grade 1 or 2 blurred vision and keratopathy occurred in 16 (40%) and 12 (30%) patients, respectively; no grade 3/4 ocular events were observed. Compared with those patients who did not receive primary prophylaxis, corticosteroid eye drop use resulted in fewer dose reductions (5% vs. 15%) and none discontinued due to ocular AEs. CONCLUSIONS: Preclinical modeling was predictive of the corneal-related symptoms seen in some patients dosed with mirvetuximab soravtansine. Primary prophylactic use of topical corticosteroid eye drops resulted in a trend toward symptomatic improvement and a reduction in ocular AE-related dose modifications in patients treated with mirvetuximab soravtansine.

Use and Effectiveness of Intraperitoneal Chemotherapy for Treatment of Ovarian Cancer.

PURPOSE: A 2006 randomized trial demonstrated a 16-month survival benefit with intraperitoneal and intravenous (IP/IV) chemotherapy administered to patients who had ovarian cancer, compared with IV chemotherapy alone, but more treatment-related toxicities. The objective of this study was to examine the use and effectiveness of IP/IV chemotherapy in clinical practice. PATIENTS AND METHODS: Prospective cohort study of 823 women with stage III, optimally cytoreduced ovarian cancer diagnosed at six National Comprehensive Cancer Network institutions. We examined IP/IV chemotherapy use in all patients diagnosed between 2003 and 2012 (N = 823), and overall survival and treatment-related toxicities with Cox regression and logistic regression, respectively, in a propensity score-matched sample (n = 402) of patients diagnosed from 2006 to 2012, excluding trial participants, to minimize selection bias. RESULTS: Use of IP/IV chemotherapy increased from 0% to 33% between 2003 and 2006, increased to 50% from 2007 to 2008, and plateaued thereafter. Between 2006 and 2012, adoption of IP/IV chemotherapy varied by institution from 4% to 67% (P < .001) and 43% of patients received modified IP/IV regimens at treatment initiation. In the propensity score-matched sample, IP/IV chemotherapy was associated with significantly improved overall survival (3-year overall survival, 81% v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared with IV chemotherapy, but also more frequent alterations in chemotherapy delivery route (adjusted rates discontinuation or change, 20.4% v 10.0%; adjusted odds ratio, 2.83; 95% CI, 1.47 to 5.47). CONCLUSION: Although the use of IP/IV chemotherapy increased significantly at National Comprehensive Cancer Network centers between 2003 and 2012, fewer than 50% of eligible patients received it. Increasing IP/IV chemotherapy use in clinical practice may be an important and underused strategy to improve ovarian cancer outcomes.

Hopelessness and complementary therapy use in patients with ovarian cancer.

BACKGROUND: Hopelessness negatively affects ovarian cancer patients' quality of life (QOL). Research validating the effects of complementary and alternative medicine (CAM) use on QOL and hope is scarce, even though QOL and hope are reasons that patients cite for using CAM therapy. Clinicians need effective, evidence-based interventions to improve QOL and reduce hopelessness. OBJECTIVE: The objectives of this study were to examine factors influencing hopelessness in patients with newly diagnosed disease, long-term survivors, and patients experiencing ovarian cancer recurrence and to examine the effects of CAM on hopelessness in the same population. METHODS: Surveys of ovarian cancer patients (N = 219) undergoing treatment at a comprehensive cancer center in the United States were analyzed. Descriptive, correlation, and multivariate analyses described variables and demonstrated the effects of sociodemographics, disease state, psychological distress, QOL, CAM use, and faith on hopelessness. RESULTS: Patients ages 65 years or older (-0.95, P = .03), with strong faith (-0.28, P = .00), and good QOL (0.11, P = .00) directly reduced hopelessness scores (mean, 3.37). Massage therapy substantially reduced hopelessness scores (-1.07, P = .02); holding age constant, employed patients were twice as likely to use massage (odds ratio, 2.09; P = .04). Patients who had newly diagnosed and recurrent ovarian cancer were more hopeless because of greater distress from symptoms and adverse effects of treatment. CONCLUSION: Patients who used massage therapy were significantly less hopeless, as were those with strong faith and well-controlled disease symptoms and treatment for adverse effects. IMPLICATIONS FOR PRACTICE: Support of spiritual needs and symptom management are important interventions to prevent and/or reduce hopelessness, especially for patients with newly diagnosed and recurrent ovarian cancer. Further research testing the positive effect of massage interventions on hopelessness is needed.

Cancer- and chemotherapy-induced anemia.

Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.

The Feasibility and Effects of Acupuncture on Quality of Life Scores During Chemotherapy in Ovarian Cancer: Results from a Pilot, Randomized Sham-Controlled Trial.

BACKGROUND: Within a pilot trial regarding chemotherapy-induced neutropenia, the secondary aim of the main study was explored. This involved measuring the effects-as shown on two key measurement scales reflecting quality of life (QoL)-of verum versus sham acupuncture on patients with ovarian cancer during chemotherapy. OBJECTIVE: The aim of this substudy was to determine the feasibility of determining the effects of verum acupuncture versus sham acupuncture on QoL in patients with ovarian cancer during chemotherapy. DESIGN: This was a randomized, sham-controlled trial. SETTING: The trial was conducted at two cancer centers. PATIENTS: Patients with ovarian cancer (N=21) who were receiving chemotherapy-primarily intravenous carboplatin and paclitaxel-participated in this substudy. INTERVENTION: The participants were given either active or sham acupuncture 1 week prior to cycle 2 of chemotherapy. There were ten sessions of acupuncture, with manual and electro-stimulation over a 4-week period. MAIN OUTCOME MEASURES: The European Organization for Research and Treatment of Cancer-Quality-of-Life Questionnaire-Core 30 Item (EORTC-QLQ-C30) and the Quality of Life Questionnaire-Ovarian Cancer Module-28 Item (QLQ-OV28) were administered to the patients at baseline and at the end of their acupuncture sessions. RESULTS: Of the original 21, 15 patients (71%) completed the study, and 93% of them completed the questionnaires. The EORTC-QLQ-C30 subscores were improved in the acupuncture arm, including the mean scores of social function (SF), pain, and insomnia (p=0.05). However, after adjusting for baseline differences, only the SF score was significantly higher in the active acupuncture arm, compared with the sham acupuncture arm (p=0.03). CONCLUSIONS: It appears feasible to conduct a randomized sham-controlled acupuncture trial measuring QoL for patients with ovarian cancer who are undergoing chemotherapy. Acupuncture may have a role in improving QoL during chemotherapy.

Acupuncture as palliative therapy for physical symptoms and quality of life for advanced cancer patients.

BACKGROUND: Acupuncture is underutilized as an adjunct cancer therapy. The main study objectives were to determine the feasibility of administering acupuncture as palliative therapy to patients with advanced ovarian or breast cancer and to assess the effect on symptoms and quality of life (QOL). METHODS: This study was a pilot, single-armed prospective clinical trial for patients with advanced cancer to receive 12 acupuncture sessions over 8 weeks with follow-up at weeks 9 and 12. Ambulatory patients with advanced ovarian or breast cancer were enrolled to receive treatments at an outpatient academic oncology center. Symptom severity was measured before and after each acupuncture session.A composite QOL assessment tool, consisting of validated instruments, was completed at 5 time points. RESULTS: Forty patients enrolled in the study. Twenty-eight patients (70%; 95% confidence interval [CI] = 53%-83%) completed 4 weeks of treatment, and 26 patients (65%; 95% CI = 48%-79%) completed 8 weeks. Eight patients (20%) withdrew before receiving acupuncture, and 6 patients (15%) discontinued treatment early because of disease progression or scheduling demands. Among all 32 assessed patients, there was self-reported improvement immediately post-treatment in anxiety,fatigue, pain, and depression and significant improvement over time for patients with anxiety (P = .001) and depression(P = .02). Among patients experiencing baseline symptoms, there was improvement in anxiety (P = .001), fatigue (P = .0002),pain (P = .0002), and depression (P = .003). QOL measures of pain severity and interference, physical and psychological distress, life satisfaction, and mood states showed improved scores during treatment, with sustained benefit at 12 weeks. CONCLUSIONS: This pilot study demonstrates that an 8-week outpatient acupuncture course is feasible for advanced cancer patients and produces a measurable benefit that should be evaluated in controlled trials.

Comparison of the quality of life of early and advanced stage ovarian cancer survivors.

OBJECTIVE: The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS). METHODS: Early and advanced OCS >3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups. RESULTS: 42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used on average 5 CAM to improve their QOL. CONCLUSION: Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors.

Acupuncture for chemotherapy-induced neutropenia in patients with gynecologic malignancies: a pilot randomized, sham-controlled clinical trial.

OBJECTIVES: The objective of this study was to investigate the effect of acupuncture administered during myelosuppressive chemotherapy on white blood cell (WBC) count and absolute neutrophil count (ANC) in patients with ovarian cancer. DESIGN: This study is a pilot, randomized, sham-controlled clinical trial. Patients received active acupuncture versus sham acupuncture while undergoing chemotherapy. A standardized acupuncture protocol was employed with manual and electrostimulation. The frequency of treatment was 2-3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. SETTING: The setting was two outpatient academic centers for patients with cancer. SUBJECTS: Twenty-one (21) newly diagnosed and recurrent ovarian cancer patients were the subjects. OUTCOME MEASURES: WBC count, ANC, and plasma granulocyte colony-stimulating factor (G-CSF ) were assessed weekly. RESULTS: The median leukocyte value in the acupuncture arm at the first day of the third cycle of chemotherapy was significantly higher than in the control arm after adjusting for baseline value (8600 cells/microL, range: 4800-12,000 versus 4400 cell/microL, range: 2300-10,000) (p = 0.046). The incidence of grade 2-4 leukopenia was less in the acupuncture arm than in the sham arm (30% versus 90%; p = 0.02). However, the median leukocyte nadir, neutrophil nadir, and recovering ANC were all higher but not statistically significantly different (p = 0.116-0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. CONCLUSIONS: We observed clinically relevant trends of higher WBC values during one cycle of chemotherapy in patients with ovarian cancer, which suggests a potential myeloprotective effect of acupuncture. A larger trial is warranted to more definitively determine the efficacy of acupuncture on clinically important outcomes of chemotherapy-induced neutropenia.

A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer.

OBJECTIVE: To determine the safety and efficacy of a novel illudin S derivative, irofulven (MGI-114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy. METHODS: The trial was an open label phase II study. Patients initially enrolled in this study were treated every 14 days with a dose of 24 mg/m2. Unexpected retinal toxicity associated with this dose and schedule lead to modification of the dosing to 0.55 mg/kg on the same schedule with a maximum individual dose of 50 mg. Dose reductions were permitted based on both hematologic and non-hematologic toxicities. RESULTS: Seventy-four women were accrued and stratified into two cohorts including 58 women with platinum-resistant disease and 16 with platinum-sensitive disease. Non-hematologic toxicities included nausea, vomiting, and fatigue. Thirty-one women had between one and six visual symptoms, most were Grade 1 and 2 in nature. The majority of visual toxicities resolved either during treatment or post-treatment with irofulven. There was one partial response in each cohort with 19 (33%) and 8 (50%) of women having stable disease in the platinum-resistant and platinum-sensitive cohorts, respectively. CONCLUSIONS: Irofulven at 24 mg/m2 on every 14-day schedule is associated with significant retinal toxicity in this patient population. Dosing at 0.55 mg/kg has persistent retinal toxicity, yet demonstrated only limited anti-tumor activity in a population of women who had received extensive prior chemotherapy.