PARAGON (ANZGOG-0903) : a phase 2 study of anastrozole in asymptomatic patients with estrogen and progesterone receptor-positive recurrent ovarian cancer and CA125 progression

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

Older age should not be a barrier to testing for somatic variants in homologous recombination DNA repair-related genes in patients with high-grade serous ovarian carcinoma

BACKGROUND: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients. METHODS: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed. Cases where somatic variants could be distinguished from germline variants were included, and analysis was restricted to those with a somatic TP53 variant, to ensure cases were HGSC. RESULTS: Of 1210 patients in GENIE, 27% (n = 325) were aged ≥70 years at testing. Patients with somatic-only PVs in BRCA2 were older compared with BRCA1 (median 71 vs 60 years, p = 0.002). Median age for 21 patients with somatic-only PVs in 11 other HR-related genes ranged from 40 to 67 years. In older patients, 7% (n = 22) had somatic BRCA1/2 PVs, and 1% (n = 2) had PVs other HR-related genes; this rate was not significantly different to younger patients (<70 years), 7% (n = 62) BRCA1/2 and 2% (n = 19) other HR-related genes (p = 0.36). The overall frequency of somatic BRCA1/2 PVs was similar in INOVATe (n = 25; 7.7%) and somatic-only BRCA2 PVs were again found in older patients compared with BRCA1 (median age: at testing, 70 vs 63 years; at diagnosis, 68 vs 60 years). CONCLUSIONS: The overall frequency of somatic-only PVs in HR-related genes was similar in older and younger patients with HGSC, highlighting the importance of somatic testing irrespective of age. Limiting somatic testing by age may exclude patients who could benefit from maintenance poly(ADP-ribose) polymerase (PARP) inhibitors

Paragon (ANZGOG-0903) phase 2 study of anastrozole in women with estrogen or progesterone receptor-positive platinum-resistant or -refractory recurrent ovarian cancer

Background: There is some evidence that a subset of patients with recurrent ovarian cancer may benefit from antiestrogen therapy. The Paragon study is a basket protocol that includes a series of phase 2 trials investigating the activity of anastrozole in patients with estrogen or progesterone receptorYpositive recurrent gynecological cancers. We report the results of treatment in patients with platinum-resistant or -refractory recurrent epithelial ovarian cancer. Methods: Postmenopausal women who had estrogen and/or progesterone receptorYpositive platinum-resistant or platinum-refractory recurrent ovarian cancer and disease measurable by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or GCIG (Gynecologic Cancer InterGroup) CA-125 criteria were eligible. Patients received anastrozole 1 mg daily until progression or unacceptable toxicity. The study was prospectively registered (ACTRN12610000796088). Results: There were 49 evaluable patients, and clinical benefit was observed in 13 (27%; 95%confidence interval [CI], 16%Y40%). Therewere no complete or partial RECIST version 1.1 responses.Clinical benefitwas associatedwith higher global quality-of-life scores.Median progression-free survival was 2.7 months (95% CI, 2.0Y2.8 months). The median duration of clinical benefit was 2.8 months (95% CI, 2.6Y5.7 months). Most patients (83%) progressed within 6months. Seven patients continued on treatment for longer than 6months. Anastrozole was well tolerated in most patients. Subgroup analysis suggested greater clinical benefit in patients with tumors with estrogen-receptor histoscore ofmore than 200, but this differencewas not statistically significant. Conclusions: A subset of patientswith estrogen- or progesterone-positive platinum-resistant or platinum-refractory recurrent epithelial ovarian cancers derives clinical benefit from anastrozole, with acceptable toxicity. The challenge remains how to identify them

Older age should not be a barrier to testing for somatic variants in homologous recombination DNA repair-related genes in patients with high-grade serous ovarian carcinoma

Background: Somatic pathogenic variants (PVs) in homologous recombination DNA repair (HR)-related genes found in high-grade serous ovarian carcinomas (HGSC) are not well-characterised in older patients (≥70 years). This may reflect low testing rates in older patients. Methods: Data from 1210 HGSC patients in AACR Project GENIE and 324 patients in an independent dataset INOVATe were analysed. Cases where somatic variants could be distinguished from germline variants were included, and analysis was restricted to those with a somatic TP53 variant, to ensure cases were HGSC. Results: Of 1210 patients in GENIE, 27% (n = 325) were aged ≥70 years at testing. Patients with somatic-only PVs in BRCA2 were older compared with BRCA1 (median 71 vs 60 years, p = 0.002). Median age for 21 patients with somatic-only PVs in 11 other HR-related genes ranged from 40 to 67 years. In older patients, 7% (n = 22) had somatic BRCA1/2 PVs, and 1% (n = 2) had PVs other HR-related genes; this rate was not significantly different to younger patients (BRCA2 PVs were again found in older patients compared with BRCA1 (median age: at testing, 70 vs 63 years; at diagnosis, 68 vs 60 years). Conclusions: The overall frequency of somatic-only PVs in HR-related genes was similar in older and younger patients with HGSC, highlighting the importance of somatic testing irrespective of age. Limiting somatic testing by age may exclude patients who could benefit from maintenance poly(ADP-ribose) polymerase (PARP) inhibitors

Bowel intussusceptions in adults: the role of imaging

Intestinal intussusception in adults is a rare condition, accounting for about 0.003-0.02 % of all hospital admissions. This condition in adults represents only 5 % of all cases of intussusceptions and is different from paediatric intussusception, which is usually idiopathic. In contrast, almost 90 % of cases in adults are secondary to various pathologies that serve as a lead point, such as polyps, Meckel's diverticulum, colonic diverticulum, or malignant or benign neoplasm. The aim of the present study was to assess the capabilities of multislice computed tomography (MSCT) in the diagnosis and correct characterisation of intussusception, especially in distinguishing between intussusceptions with a lead point and those without. Indeed, although the MSCT findings that help to differentiate between lead point and non-lead point intussusceptions have not been well studied, abdominal MSCT remains the most sensitive radiological tool to confirm bowel intussusceptions. Moreover, differentiating intussusceptions with a lead point condition from those without is crucial for directing the patient towards the most appropriate treatment, avoiding surgery when not necessary