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PURPOSE ATHENA (ClinicalTrials.gov identifier: NCT03522246 ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo. METHODS Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.

Objective To describe the incidence of low-volume, ultrastage-detected metastases in sentinel lymph nodes (SLNs) identified at surgical staging for endometrial carcinoma and to correlate it with depth of myoinvasion (DMI) and tumor grade. Methods We reviewed all patients who underwent primary surgery for endometrial carcinoma with successful mapping of at least one SLN at our institution from 9/2005-12/2011. All patients underwent a cervical injection for mapping. The SLN ultrastaging protocol involved cutting an additional two adjacent 5-μm sections at each of two levels, 50-μm apart, from each paraffin block lacking metastatic carcinoma on routine H&E. At each level, one slide was stained with H&E and with immunohistochemistry (IHC) using anti-cytokeratin AE1:AE3. Micrometastases (tumor deposits <0.2mm and ≤2mm) and isolated tumor cells (≤0.2mm) were classified as low-volume, ultrastage-detected metastases if pathologic ultrastaging was the only method allowing detection of such nodal disease. Results Of 508 patients with successful mapping, 413(81.3%) had endometrioid carcinoma. Sixty-four(12.6%) of 508 patients had positive nodes: routine H&E detected 35 patients(6.9%), ultrastaging detected an additional 23 patients(4.5%) who would have otherwise been missed (4 micrometastases, 19 isolated tumor cells), and 6 patients(1.2%) had metastatic disease in their non-SLNs. The incidence of low-volume, ultrastagedetected nodal metastases in grade 1, 2, and 3 patients was 3.8%, 3.4%, and 6.9%, respectively. The frequency of low-volume, ultrastage-detected metastases in patients with a DMI of 0, <50%, and ≥50% was 0.8%, 8.0%, and 7.4%, respectively. Lymphovascular invasion was present in 20(87%) of the cases containing low-volume, ultrastage-detected metastases in the lymph nodes. Conclusions SLN mapping with pathologic ultrastaging in endometrial carcinoma detects additional low-volume metastases(4.5%) that would otherwise go undetected with routine evaluations. Our data support the incorporation of pathologic ultrastaging of SLNs in endometrial carcinoma with any degree of myoinvasion. The oncologic significance of lowvolume nodal metastases requires long-term follow-up.