2021
DOI: 10.1016/s0140-6736(20)32554-x
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Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial

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Cited by 152 publications
(112 citation statements)
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“…Consistent with our in vitro data, NCC_CDS1_X1_C1 and NCC_CDS2_C1 tumor explants from adavosertib-treated mice demonstrated a decrease in CDK1 phosphorylation (Y15) and increased PARP cleavage compared to vehicle control (Figure 4E-F). These in vivo studies further validate WEE1 as a therapeutic vulnerability in CIC-DUX4 sarcomas that can be readily targeted through clinically advanced WEE1 inhibitors, including adavosertib (28, 37). Collectively, these data demonstrate a mechanism-based therapeutic strategy to precisely and effectively target CIC-DUX4 sarcomas in patients.…”
Section: Resultsmentioning
confidence: 69%
See 1 more Smart Citation
“…Consistent with our in vitro data, NCC_CDS1_X1_C1 and NCC_CDS2_C1 tumor explants from adavosertib-treated mice demonstrated a decrease in CDK1 phosphorylation (Y15) and increased PARP cleavage compared to vehicle control (Figure 4E-F). These in vivo studies further validate WEE1 as a therapeutic vulnerability in CIC-DUX4 sarcomas that can be readily targeted through clinically advanced WEE1 inhibitors, including adavosertib (28, 37). Collectively, these data demonstrate a mechanism-based therapeutic strategy to precisely and effectively target CIC-DUX4 sarcomas in patients.…”
Section: Resultsmentioning
confidence: 69%
“…Future studies should focus on rational combinatorial strategies to enhance DNA damage and potentially augment WEE1 inhibitor responses. Adavosertib is currently being evaluated in multiple tumor histologies and is proven safe as monotherapy or in combination with other conventional targeted and chemotherapy agents as well as radiotherapy (11, 27, 28, 37). Thus, adavosertib therapy is potentially a safe and efficacious therapy (28) that can be rapidly employed in the clinic to more effectively target CIC-DUX4 sarcomas.…”
Section: Resultsmentioning
confidence: 99%
“…A plethora of studies with emerging targeted therapies have reported promising data in heavily pretreated late-stage ovarian cancer, but relatively few have included patients with confirmed Pt-Rf disease. These patients have few therapy options, but due to their poor prognosis they are under-represented, accounting for only around 10% of the total population recruited in many clinical studies [46,47], including our own. Several early-phase trials with targeted therapies have reported lower ORR in subgroups of patients with Pt-Rf disease than in the overall study population [46,48,49], indicating that response may be related to platinum sensitivity status-this is the reverse of our findings.…”
Section: Discussionmentioning
confidence: 99%
“…Adverse events (AEs) included diarrhea (76.5%), fatigue (64.7%), nausea (61.8%), anemia (67.6%), low platelet count (17.6%), or low neutrophil count (32.4%). ( 13) Progression-free survival (PFS) was longer with adavosertib plus gemcitabine (median 4•6 months vs 3•0 months with placebo plus gemcitabine in platinum-resistant or platinum-refractory recurrent ovarian cancer patients at the phase 2 trial NCT02151292 (14). Adding adavosertib to chemotherapy improved PFS [median, 7.9 vs. 7.3 months in patients with TP53-mutated, platinumsensitive ovarian cancer treated with adavosertib (A+C) plus carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel group(P+C) in the phase II clinical trial NCT01357161.…”
Section: Wee1 Inhibitorsmentioning
confidence: 99%