Before consideration of high-dose therapy for recurrent/persistent advanced ovarian cancer, patients should undergo debulking surgery or chemotherapy to achieve a minimal disease state. Patients with platinum-resistant, bulky disease should not be transplanted. The optimal patients for this therapy may be those with minimal disease responsive to initial chemotherapy.

Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase II investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients > 18 years of age with untreated early unfavorable or advanced stage disease were eligible for treatment. Thirty patients with either early unfavorable (n=12) or advanced (n=18) stage cHL were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4-6 cycles depending on stage and bulk. Twelve had either large mediastinal masses and/or bulky disease (>10 cm). Following pembrolizumab monotherapy, 11 patients (37%) demonstrated CMR's, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography/computed tomography scanning (PET-CT) had >90% reductions in metabolic tumor volume. All patients achieved CMR following 2 cycles of AVD and maintained their responses at end of treatment. With a median follow-up of 22.5 months (range: 14.2-30.6) there have been no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well-tolerated. The most common immune-related adverse events were grade 1 rash (n=6), and grade 2 infusion reactions (n=4). One patient had a reversible grade 4 transaminitis and a second had a reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD proved both highly effective and safe in newly diagnosed cHL patients including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

A B S T R A C T PurposeCisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes. Patients and MethodsEligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m 2 on days 1 through 4 and gemcitabine 1,000 mg/m 2 on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest. ResultsOf 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor-negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)-751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes. ConclusionCombination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen.