Peter Vuylsteke

Molecular Results and Potential Biomarkers Identified from the Phase 3 MILO/ENGOT-ov11 Study of Binimetinib versus Physician Choice of Chemotherapy in Recurrent Low-Grade Serous Ovarian Cancer

Abstract Purpose: We present the results of a post hoc tumor tissue analysis from the phase 3 MILO/ENGOT-ov11 study (NCT01849874). Patients and Methods: Mutation/copy-number analysis was performed on tissue obtained pre-randomization. The Kaplan–Meier method was used to estimate progression-free survival (PFS). Unbiased univariate analysis, Cox regression, and binary logistic regression were used to test associations between mutation status and outcomes, including PFS and binary response by local RECIST 1.1. Results: MILO/ENGOT-ov11 enrolled 341 patients, ranging in age from 22 to 79, from June, 2013 to April, 2016. Patients were randomized 2:1 to binimetinib or physician's choice of chemotherapy (PCC). The most commonly altered gene was KRAS (33%). In 135 patients treated with binimetinib with response rate (RR) data, other detected MAPK pathway alterations included: NRAS (n = 11, 8.1%), BRAF V600E (n = 8, 5.9%), RAF1 (n = 2, 1.5%), and NF1 (n = 7, 5.2%). In those with and without MAPK pathway alterations, the RRs with binimetinib were 41% and 13%, respectively. PFS was significantly longer in patients with, compared with those without, MAPK pathway alterations treated with binimetinib [HR, 0.5; 95% confidence interval (CI) 0.31–0.79]. There was a nonsignificant trend toward PFS improvement in PCC-treated patients with MAPK pathway alterations compared with those without (HR, 0.82; 95% CI, 0.43–1.59). Conclusions: Although this hypothesis-generating analysis is limited by multiple testing, higher RRs and longer PFS were seen in patients with low-grade serous ovarian cancer (LGSOC) treated with binimetinib, and to a lesser extent in those treated with PCC, who harbored MAPK pathway alterations. Somatic tumor testing should be routinely considered in patients with LGSOC and used as a future stratification factor.

Impact of the COVID-19 Pandemic on Cervical Cancer Treatment Delays in Botswana

PURPOSE Although the majority of cervical cancer cases are in sub-Saharan Africa, little is known regarding how the COVID-19 pandemic affected cancer care in this context. Drawing from robust longitudinal data, this study aimed to assess cervical cancer treatment patterns in Botswana before and during the pandemic. METHODS Longitudinal clinical and patient-reported data from a cohort of over 1,000 patients seen at a gynecologic oncology multidisciplinary team clinic in Botswana were used to evaluate treatment initiation patterns before (April 2018-December 2019) and during (April 2020-December 2021) the pandemic. The primary outcome was timeliness of treatment, defined as the number of days between the patient's first clinic visit and treatment initiation date, and categorized as timely (≤30 days), delayed (>30 days), or no treatment. The primary exposure was time of visit (pre–COVID-19 v COVID-19), defined by the month of the clinic visit. RESULTS Of the 559 patients with cervical cancer diagnosed during the study period, 336 were seen pre–COVID-19, and 223 were seen during the COVID-19 period. During the pandemic, a higher proportion of patients experienced treatment delays (66.4%) or received no treatment (24.2%), compared with the pre–COVID-19 period (35.7% and 9.8%, respectively; P < .001). Multivariable regression models indicated that patients seen during the pandemic were 10 times more likely to experience treatment delays (adjusted odds ratio [aOR], 10.01 [95% CI, 5.69 to 17.62]) and 14 times more likely to receive no treatment (aOR, 14.16 [95% CI, 7.14 to 28.10]). CONCLUSION The pandemic exacerbated treatment delays for patients with cervical cancer in Botswana. There is a need for evidence-based strategies to address these treatment delays, considering the disproportionate burden of disease and persistent disparities in access to care in Botswana and other low- and middle-income countries.

Benchmarking of the Cervical Cancer Care Cascade and Survival Outcomes After Radiation Treatment in a Low- and Middle-Income Country Setting

Delays in care for patients with cervical cancer in Botswana can be benchmarked using a multidisciplinary clinic model.

A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer) is a Phase 3 study during which patients with recurrent or persistent low-grade serous (LGS) carcinomas of the ovary, fallopian tube or primary peritoneum will receive either investigational study drug MEK162 or a chemotherapy chosen by the physician (liposomal doxorubicin, paclitaxel or topotecan). Patients will be followed to compare the effectiveness of the study drug to that of the selected chemotherapies. Patients may be eligible to crossover from physician's choice chemotherapy to MEK162 if they meet certain inclusion criteria including centrally confirmed disease progression. Approximately 360 patients from North America, Europe and Australia will be enrolled in this study.