Characterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

Clear-cell carcinoma of the ovary (CCCO) is a distinct entity of epithelial ovarian cancer in terms of clinical, histopathological, or genetic features. The incidence of CCCO is different by ethnicity but the reason is not clear yet. Overall prognosis of CCCO is good because most CCCO is found in stage I. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. The same is true for recurrent disease. Therefore, genetic analysis of CCCO is important to find the right target(s) and better therapeutic approaches. Because of its rarity, international collaboration is necessary to conduct randomized clinical trials for CCCO.

Stage, performance status, CA-125 level, LVSI, and myometrial invasion were associated with poor prognoses. Pelvic lymphadenectomy was associated with improved survival, and may be necessary for the surgical management of UCS.

According to the specified primary objective, a regimen of cisplatin, paclitaxel and bevacizumab was tolerable in Japanese patients and demonstrated encouraging activity in this small single-arm study.

No abstract

Veliparib (ABT‐888) is a potent, orally bioavailable poly(ADP‐ribose) polymerase‐1 and ‐2 inhibitor. This phase 1 study evaluated the tolerability, pharmacokinetic profile, safety, and preliminary antitumor activity of single‐agent veliparib in Japanese patients with advanced solid tumors. Eligible patients were assigned to treatment with veliparib at 200 or 400 mg dose; veliparib was self‐administered orally twice daily on days 1–28 of 28‐day cycles. Dose escalation, following a 3 + 3 design, defined dose‐limiting toxicities, the maximum tolerated dose, and the recommended phase 2 dose. Sixteen patients were enrolled (median age, 59 years). Fourteen patients had high‐grade serous ovarian cancer, one had primary peritoneal cancer, and one had BRCA‐mutated breast cancer. The most frequent treatment‐emergent adverse events were nausea and vomiting (93.8% each), decreased appetite (62.5%), abdominal pain, diarrhea, and malaise (31.3% each). A grade ≥3 toxicity was observed in 50% of patients; one patient each in the 200 mg (n = 4) and 400 mg (n = 12) cohorts experienced serious adverse events. Dose‐limiting toxicities were observed for one patient at the 400 mg dose. No toxicities leading to death were reported. The recommended phase 2 dose was defined as 400 mg twice daily. The veliparib pharmacokinetic profile was consistent with that reported for the Western population. Two patients, both with ovarian cancer, had a RECIST partial response. Veliparib monotherapy showed manageable tolerability and safety profiles and a predictable pharmacokinetic profile at a 400 mg twice‐daily dose, and supports the inclusion of Japanese patients in the multinational phase 3 study (NCT02470585).

PURPOSE Anaplastic lymphoma kinase ( ALK) rearrangement is a well-known driver oncogene in non–small-cell lung cancer and has also been identified in other types of tumors. However, there is limited evidence on the clinical response to ALK tyrosine kinase inhibitors (TKIs), such as alectinib and crizotinib, in rare tumors with ALK fusion. We evaluated the therapeutic effect of ALK-TKIs in rare ALK-rearranged tumors. PATIENTS AND METHODS Between April 2012 and April 2019, clinical outcomes and characteristics of patients with ALK-rearranged nonlung solid tumors who received ALK-TKIs (alectinib and/or crizotinib) outside of clinical trials were reviewed. Expression and/or rearrangement of ALK was evaluated by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing. The tumor response was assessed according to RECIST (version 1.1). Progression-free survival was estimated from initial ALK-TKI initiation until progression. RESULTS We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. CONCLUSION This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

PIK3CA mutations are common activating mutations associated with breast cancer (occurring in 20–30% of all cases) and are potent predictive markers for responses to PI3K inhibitors. Thus, it is important to develop sensitive methods to detect these mutations. We established a novel detection method using a quenching probe (QP) system to identify PIK3CA mutations, using DNA from 309 breast cancer tissues. In a developmental cohort, we determined the optimal detection threshold of the QP system with human tumor DNA from 119 freshly frozen tumor samples. We found a 96% concordance rate with the QP system between DNA from 26 matching fresh‐frozen specimens and formalin‐fixed paraffin‐embedded (FFPE) specimens from the same patients, and known PIK3CA mutation status in the developmental cohort. In a validation cohort, we evaluated whether the threshold for judging mutations using the QP system with frozen specimen‐derived DNA was applicable with FFPE‐derived DNA. In the validation cohort, 30 DNA samples from 190 FFPE‐derived DNA samples with known PIK3CA mutation status were analyzed by direct sequencing (DS) and droplet digital PCR, in a blinded manner. The sensitivity and specificity of the droplet digital PCR results were 100% and 100% (QP system), and 60% and 100% (DS), respectively. We also analyzed the relationship between clinical outcomes and the PIK3CA mutational status of 309 breast cancer samples, including the developmental cohort and validation cohort samples. Multivariate analysis suggested that PIK3CA mutations, especially H1047R, were prognostic factors of relapse‐free survival. Our novel detection system could be more useful than DS for detecting clinical PIK3CA mutations.