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Background: Hormonal therapies are commonly prescribed to patients with metastatic granulosa cell tumours (GCT), based on high response rates in small retrospective studies. Aromatase inhibitors (AIs) are reported to have high response rates and an accepted treatment option. We report the results of a phase 2 trial of an AI in recurrent/metastatic GCTs., Methods: 41 patients with recurrent ER/PR + ve GCT received anastrozole 1 mg daily until progression or unacceptable toxicity. The primary endpoint was clinical benefit rate (CBR) at 12 weeks, evaluated by RECIST1.1 criteria. Secondary endpoints included progression-free survival (PFS), CBR duration, quality of life and toxicity., Results: The CBR at 12 weeks in 38 evaluable patients was 78.9%, which included one (2.6%; 95% CI: 0.5-13.5%) partial response and 76.3% stable disease. Two additional patients without measurable disease were stable, based on inhibin. Median PFS was 8.6 m (95% CI 5.5-13.5 m). There were delayed responses observed after 12 weeks with a total of 4 pts. (10.5%; 95% CI 4.2%-24.1%) with a RECIST partial response; 23 (59%) patients were progression-free at 6 months. The adverse effects were predominantly low grade., Conclusions: This is the first prospective trial of hormonal therapy in GCTs. Although there was a high CBR, the objective response rate to anastrozole was much lower than the pooled response rates of >70% to AIs reported in most retrospective series and case reports. PARAGON demonstrates the importance of prospective trials in rare cancers and the need to reconsider the role of AIs as single agents in GCTs., Competing Interests: Declaration of Competing Interest SB: Institutional grants from Astrazeneca, Tesaro, GSK. Personal fees for advisory boards/lectures: Amgen, Astrazeneca, Clovis, Genmab, GSK, Immunogen, Mersana, MSD, Merck Sereno, Mersana, Oncxerna, Pfizer, Roche, Takeda, Tesaro, outside the submitted work. KS: Research funding to institution, Bayer and Amgen. Personal fees from Merck, Amgen, Servier, BMS, IPSEN, Competitive Drug Development, outside the submitted work. AC: Grants from Cancer Research UK and Astrazeneca, personal fees from AstraZeneca, GSK, Tesaro, Clovis Oncology, Eisai, outside the submitted work. RL: Personal fees from Tesaro and Roche outside the submitted work. MH: Research funding to institution Merck, BMS, Clovis Oncology. Honoraria for Advisory Boards/ Lectures: Amgen, AZ, Clovis Oncology, GSK, MSD, Roche outside the submitted work. CG: Research funding to institution: AstraZeneca, Novartis, Aprea, Nucana, Tesaro, BerGen Bio. Honorary for advisory boards/lectures: Roche, AstraZeneca, MSD, GSK, Tesaro, Nucana, Clovis, Foundation One, Sierra Oncology, Cor2Ed, Takeda. PS: Grant from University of Sydney. RE: Personal fees from Arquer Diagnostics, GSK, Clovis oncology outside submitted work. MF: personal fees from Astra Zeneca, MSD, GSK, Tesaro, Lilly, Takeda and Novartis; institutional grants from Astra Zeneca, Novartis and Beigene, other from Abbvie and ACT Genomics outside the submitted work. All other authors (MT, ROC, DM, SN, VMM, TB, JCG, PTG, OM, LA, CK, KC, LD, NB) report no disclosures of interest., (Copyright © 2021. Published by Elsevier Inc.)

Objective: A subset of patients with recurrent ovarian cancer (ROC) may benefit from antiestrogen therapy with higher response rates reported in tumors that are strongly estrogen receptor (ER)-positive (ER⁺). PARAGON is a basket trial that incorporates 7 phase 2 trials investigating the activity of anastrozole in patients with ER⁺ and/or progesterone receptor (PR)-positive (PR⁺) recurrent/metastatic gynecological cancers., Methods: Postmenopausal women with ER⁺ and/or PR⁺ ROC, who were asymptomatic and had cancer antigen 125 (CA125) progression after response to first line chemotherapy, where chemotherapy was not clinically indicated. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity., Results: Fifty-four patients were enrolled (52 evaluable). Clinical benefit at three months (primary endpoint) was observed in 18 patients (34.6%; 95% confidence interval [CI]=23%-48%). Median progression-free survival (PFS) was 2.7 months (95% CI=2.1-3.1). The median duration of clinical benefit was 6.5 months (95% CI=2.8-11.7). Most patients progressed within 6 months of starting anastrozole but 12 (22%) continued treatment for longer than 6 months. Anastrozole was well tolerated. In the exploratory analysis, ER histoscores and the intensity of ER staining did not correlate with clinical benefit rate or PFS., Conclusion: A subset of asymptomatic patients with ER⁺ and/or PR⁺ ROC and CA125 progression had durable clinical benefit on anastrozole, with acceptable toxicity. Anastrozole may delay symptomatic progression and the time to subsequent chemotherapy. The future challenge is to identify the subset of patients most likely to benefit from an aromatase inhibitor and whether the clinical benefit could be increased by the addition of other agents., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Background: The aim of chemotherapy in patients with platinum resistant ovarian cancer is palliation. Patients' experience of symptoms is not well documented, and the impact of treatment on symptoms has not been evaluated in clinical trials. We report symptom burden and treatment outcomes from stage 1 of the Gynecological Cancer Intergroup (GCIG) Symptom Benefit Study., Methods: One hundred twenty-six patients receiving palliative chemotherapy completed 5 validated health-related quality-of-life questionnaires before starting treatment and before each cycle. They also reported their expected and perceived benefits from treatment. Physicians documented the reasons for treatment and adverse events including symptoms at baseline and estimated the number of cycles of treatment that patients would receive., Results: Palliation was the major reason for chemotherapy. At baseline, all patients were symptomatic (almost 70% had ≥9 symptoms). Patients had high expectation of benefit from treatment. Only 41% of patients received the predicted number of cycles with most stopping early (≤2 cycles) due to progression, death, or adverse effects. Treatment was associated with significant toxicity, with discordance between patient report and physician grading. Although RECIST response rates were low (8.5%), 40% of the patients were reported to have had a clinical benefit and almost 50% of symptomatic patients also reported symptom improvement., Conclusions: Patients had a complex array of symptoms and significant symptom burden, which was commonly the reason for treatment. Although chemotherapy improved symptoms in about half of the patients, many did not benefit and progressed rapidly. Our findings support research into the use of patient reported outcome measures to document symptoms, adverse events, and subjective benefit, both in clinical trials and in clinical practice, in this patient population. Our findings highlight the need to develop prognostic models to better select patients for treatment, and this is an aim of stage 2 of the GCIG Symptom Benefit Study.

Objective: The aim of this study was to determine the optimal patient-reported outcome measure (PROM) for assessing symptom benefit in trials of palliative chemotherapy for women with symptomatic ovarian cancer., Methods: Candidate PROMs were EORTC QLQ-C30 plus ovarian-specific QLQ-OV28, Functional Assessment of Cancer Therapy-Ovarian (FACT-O), FACT Ovarian Symptom Index (FOSI), and gynecologic cancer-specific Symptom Representation Questionnaire. Predefined optimality criteria were inclusion of all symptoms necessary for the specified purpose, recall period covering typical length of palliative chemotherapy, numerical item rating scales, and all necessary symptoms included in a single symptom index. Qualitative and quantitative methods were applied to data from stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study to determine the set of necessary symptoms and to objectively assess candidate PROMs against the optimality criteria., Results: Ten necessary symptoms were identified: pain, fatigue, abdominal bloating/discomfort, sleep disturbance, bowel disturbance, nausea and vomiting, shortness of breath, poor appetite, urinary symptoms, and weight changes. Although QLQ-C30 and QLQ-OV28 together cover all these symptoms, they split them into numerous scales, dissipating potential symptom-benefit signal. Conversely, FACT-O does not cover all necessary symptoms and contains many other HRQoL-related items and treatment side effects, diluting potential symptom-benefit signal when summed into scales. Item response scales and composite scoring of all candidate PROMs were suboptimal to our specific purpose. We therefore developed a new PROM, the Measure of Ovarian Symptoms and Treatment (MOST) concerns, to provide optimal measurement for the specified purpose., Conclusions: This article documents the development of the MOST, a new PROM designed to assess patient-reported benefits and burden as end points in clinical trials of palliative chemotherapy for women with symptomatic ovarian cancer. The validity, reliability, and statistical efficiency of the MOST, relative to the best candidate scales of existing PROMs, will be assessed in the stage 2 of Gynecologic Cancer Intergroup Symptom Benefit Study.