Activity

Objective This study investigated the safety and tolerability of lifastuzumab vedotin (DNIB0600A) (LIFA), an antibody-drug conjugate, in patients with recurrent platinum-sensitive ovarian cancer (PSOC). Methods In this open-label, multicenter phase 1b study, LIFA was administered intravenously once every 3 weeks (Q3W) with starting dose 1.2 mg/kg in a 3 + 3 dose-escalation scheme. All patients received carboplatin at dose AUC 6 mg/mL·min (AUC6) Q3W for up to 6 cycles. Dose expansion cohorts were enrolled ± bevacizumab 15 mg/kg Q3W. Results Patients received LIFA at 1.2, 1.8, and 2.4 mg (n = 4, 5, and 20, respectively) with carboplatin. The maximum tolerated dose was not reached. The recommended phase 2 dose (RP2D) was LIFA 2.4 mg/kg + carboplatin AUC6 (cycles 1-6), with or without bevacizumab 15 mg/kg. Twelve patients received RP2D with bevacizumab. All patients experienced ≥1 adverse event (AE). The most common treatment-related AEs were neutropenia, peripheral neuropathy, thrombocytopenia, nausea, fatigue, anemia, diarrhea, vomiting, hypomagnesaemia, aspartate aminotransferase increased, alanine aminotransferase increased, and alopecia. Thirty-four (83%) patients experienced grade ≥ 3 AEs, the most frequent of which were neutropenia and thrombocytopenia. Nine (22%) patients experienced serious AEs. Pulmonary toxicities (34%), considered a potential risk of LIFA, included one patient who discontinued study treatment due to grade 2 pneumonitis. The median duration of progression-free survival was 10.71 months (95% CI 8.54, 13.86) with confirmed complete/partial responses in 24 (59%) patients. Pharmacokinetics of mono-therapy LIFA was similar in combination therapy. Conclusion LIFA in combination with carboplatin ± bevacizumab demonstrated acceptable safety and encouraging activity in PSOC patients.Objective To assess trends in guideline-adherent fertility-sparing surgery (GA-FSS) for early-stage cervical cancer relative to Patient Protection and Affordable Care Act (ACA) implementation. Methods National Cancer Database patients treated for Stage IA1-IB1 cervical cancer from 2004 to 2016 were included. Multivariable logistic regression was used to determined trends in GA-FSS relative to the ACA and identify patient factors independently associated with GA-FSS. Results Odds of GA-FSS increased in the post- compared to pre-ACA cohort (aOR = 1.65; 95%CI 1.34-2.03). Decreasing age, Asian/Pacific Islander race, higher education and income levels, more recent treatment year, and lower clinical stage were independently associated with increased odds of receiving GA-FSS. In the pre- and post-ACA samples, decreasing age (per 1 year age increase; pre-ACA aOR = 0.87, 95%CI0.85-0.90; post-ACA aOR = 0.85, 95%CI0.83-0.87), higher education level (top vs. lowest education quartile; pre-ACA aOR = 2.08, 95%CI1.19-3.65; post-ACA aOR = 2.00, 95%CI1.43-2.80), and lower clinical stage (stages IA2 [pre-ACA aOR = 0.19, 95%CI0.09-0.41; post-ACA aOR = 0.29, 95%CI0.19-0.45] and IB1 [pre-ACA aOR = 0.06, 95%CI0.06-0.16; post-ACA aOR = 0.16, 95%CI 0.12-0.20] relative to stage IA1) were independently associated with increased odds of GA-FSS receipt. After the ACA, Asian/Pacific Islander race (aOR = 2.81, 95%CI 1.81-4.36) and more recent treatment year (Spearman’s ρ = 0.0348, p-value = 0.008) were also independently associated with increased odds of GA-FSS receipt. When adjusted for the pre- vs. post-ACA treatment periods, Medicaid patients were less likely to undergo GA-FSS than privately-insured patients (aOR = 1.65; 95%CI1.34-2.03). Conclusions Patients were more likely to receive GA-FSS post-ACA. Though the proportion of publicly-insured women increased after ACA implementation, women on Medicaid remained less likely to receive GA-FSS than women with private insurance.Objective To investigate the efficacy and safety of pembrolizumab in women with recurrent small cell neuroendocrine tumors of the lower genital tract. check details Methods We conducted an open-label, investigator-initiated phase II basket trial of pembrolizumab 200 mg intravenously every 3 weeks in patients with rare tumors (ClinicalTrials.gov NCT02721732). The trial had prespecified cohorts, including small cell malignancies of extrapulmonary origin. Eligibility criteria included disease progression during standard treatment in the 6 months before study enrollment. Patients were enrolled from February 2017 to February 2019. The primary endpoint was the proportion of patients alive without progression at 27 weeks. Response to pembrolizumab was evaluated every 9 weeks (3 cycles) with radiographic imaging. Results Seven women with gynecologic extrapulmonary small cell carcinoma were enrolled, 6 with cervical and 1 with vulvar carcinoma. No patient was progression free at 27 weeks. At first radiologic assessment, 1 patient had stable disease, while 6 had progression. The single patient with stable disease at 6 weeks had disease progression at 14 weeks. The median progression-free interval was 2.1 months (range 0.8-3.3 months). Severe treatment-related adverse events (≥grade 3) were seen in 2 of 7 patients (29%); 1 patient had grade 3 asymptomatic elevation of serum alkaline phosphatase, and 1 had grade 3 asymptomatic elevation of serum alanine aminotransferase. Conclusions Pembrolizumab alone showed minimal activity in women with recurrent small cell neuroendocrine tumors of the lower genital tract. Treatment was well tolerated in the majority of study participants, and the rate of severe adverse events was low.Objective SARS-CoV-2 pandemic is continuing to spread. There are growing concerns on the impact of COVID-19 in cancer patients. Several papers reporting recommendations and guidelines are published. But few data on cancer patients affected by COVID-19 are available. Methods This is a retrospective study including all consecutive patients affected by gynecological cancer who developed COVID-19. All patients were treated in an academic setting (in Milan, Lombardy, Italy) between February and March 2020. Results Overall, 355 patients had active treatment during the study period due to newly diagnosed or recurrent gynecological disease. Among those, 19 (5.3%) patients affected developed COVID-19. All patients were asymptomatic at the time of COVID-19 detection. Six patients were diagnosed before starting planned treatments; while the remaining 13 were diagnosed for COVID-19 after their started their treatments. Considering the first group of six patients, one patient died due to COVID-19 3 days after the diagnosis; while the other patients recovered from COVID-19 after a median of three weeks.