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PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated clinical benefit for patients with solid tumors bearing germline or somatic alterations in DNA damage response (DDR) genes. Somatic alterations in DDR genes are common in advanced urothelial cancer, raising the possibility that PARP inhibition may confer therapeutic benefit in a molecularly selected subgroup of patients with metastatic urothelial cancer (mUC). METHODS: This single-arm, open-label, multi-institutional, investigator-initiated phase II study evaluated the antitumor activity of olaparib 300 mg twice a day in participants with mUC harboring somatic DDR alterations. Patients had progressed despite previous platinum-based chemotherapy, or were cisplatin-ineligible, and harbored somatic alterations in at least one of a prespecified list of DDR genes. The primary end point was objective response rate; secondary end points were safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Overall, 19 patients with mUC were enrolled and received olaparib; the trial closed early before slow accrual. The median age was 66 years (range, 45-82). Nine patients (47.4%) had received previous cisplatin chemotherapy. Ten patients (52.6%) had alterations in homologous recombination (HR) genes: eight patients (42.1%) had pathogenic BRCA2 mutations and two patients carried alterations in other HR genes. No patients achieved a partial response although six patients achieved stable disease lasting 2.13-16.1 months (median, 7.69). The median PFS was 1.9 months (range, 0.8-16.1), and the median OS was 9.5 months (range, 1.5-22.1). CONCLUSION: Single-agent olaparib showed limited antitumor activity in patients with mUC and DDR alterations, which may be related to poorly characterized functional implications of particular DDR alterations and/or cross-resistance with platinum-based chemotherapy in a disease where such therapy represents standard first-line treatment. [ABSTRACT FROM AUTHOR]

PURPOSE: Tumors with neomorphic mutations in IDH1/2 have defective homologous recombination repair, resulting in sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. The Olaparib Combination trial is a phase II, open-label study in which patients with solid tumors harboring IDH1/2 mutations were treated with olaparib as monotherapy, with objective response and clinical benefit rates as the primary end points. METHODS: Ten patients with IDH1/2-mutant tumors by next-generation sequencing were treated with olaparib 300 mg twice daily. RESULTS: Three of five patients with chondrosarcomas had clinical benefit, including one patient with a partial response and two with stable disease lasting > 7 months. A patient with pulmonary epithelioid hemangioendothelioma had stable disease lasting 11 months. In contrast, clinical benefit was not observed among four patients with cholangiocarcinoma. CONCLUSION: These results indicate preliminary activity of PARP inhibition in patients with IDH1/2-mutant chondrosarcoma and pulmonary epithelioid hemangioendothelioma. Further studies of PARP inhibitors alone and in combination in this patient population are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Financial toxicity (FT) adversely influences patient quality of life and is a barrier to clinical trial enrollment. Early-phase clinical trials (EPCTs) recruit patients who may have high baseline FT and require additional visits and procedures, potentially increasing FT., Methods: In this prospective survey study, we sought to assess FT at baseline and after 2 months among patients with advanced solid malignancies participating in EPCTs. Participants were age 18 years and older, were English-speaking, and were treated at the Yale Cancer Center (Yale) and the Tisch Cancer Institute at Mount Sinai (Mount Sinai). At the time of consent and 2 months later, patients completed a sociodemographic questionnaire as well as the 11-item validated Comprehensive Score for Financial Toxicity (COST) instrument. Primary outcomes were baseline COST score and change in COST score from baseline to 2 months. Lower score is associated with higher FT., Results: One hundred forty-six patients completed survey 1. Mean age was 61.5 years and 50.7% were male. The most common histologies were lung (17.8%), colorectal (16.4%), and breast (12.3%) cancers. Mean baseline COST score was 22.12 (standard deviation, 8.01). FT was associated with being a primary wage earner ( P = .044) and inversely associated with age ( P = .025). Seventy-one patients completed survey 2. Among 71 patients who completed both surveys, there was no significant difference in COST score between surveys 1 and 2 ( P = .28). Race, ethnicity, education, and household income were not associated with baseline COST score or change in FT., Conclusion: Moderate FT was reported at baseline and on trial among EPCT participants. No change in FT was observed between time points. Additional efforts should be made to decrease FT associated with EPCT participation to maximize access to novel therapies.

Purpose: To understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision making was influenced by the pandemic., Methods: An online survey was conducted between March 24 and April 29, 2020., Results: A total of 343 oncologists from 28 countries participated. The median age was 43 years (range, 29-68 years), and the majority were male (62%). At the time of the survey, nearly all participants self-reported an outbreak in their country (99.7%). Personal protective equipment was available to all participants, of which surgical mask was the most common (n = 308; 90%). Telemedicine, in the form of phone or video encounters, was common and implemented by 80% (n = 273). Testing patients with cancer for COVID-19 via reverse transcriptase polymerase chain reaction before systemic treatment was not routinely implemented: 58% reported no routine testing, 39% performed testing in selected patients, and 3% performed systematic testing in all patients. The most significant factors influencing an oncologist's decision making regarding choice of systemic therapy included patient age and comorbidities (81% and 92%, respectively). Although hormonal treatments and tyrosine kinase inhibitors were considered to be relatively safe, cytotoxic chemotherapy and immune therapies were perceived as being less safe or unsafe by participants. The vast majority of participants stated that during the pandemic they would use less chemotherapy, immune checkpoint inhibitors, and steroids. Although treatment in neoadjuvant, adjuvant, and first-line metastatic disease was less affected, most of the participants stated that they would be more hesitant to recommend second- or third-line therapies in metastatic disease., Conclusion: Decision making by oncologists has been significantly influenced by the ongoing COVID-19 pandemic.