O001/#504 Durvalumab, in combination with and following chemoradiotherapy, in locally advanced cervical cancer: results from the phase 3 international, randomized, double-blind, placebo-controlled calla trial

• DOI: 10.1136/ijgc-2022-igcs.3
• Publication Date: 2022-12-25T16:00:01Z
• Authors: Bradley Monk; Takafumi Toita; Xiaohua Wu; Juan Carlos Limón; Qi Zhou; Rafal Tarnawski; Masaki Mandai; Ronnie Shapira-Fr...; Umesh Mahantshetty; Maria Del Pilar E...; Francisco Ramirez...; Szilvia Varga; Manuel Humberto L...; Jung-Yun Lee; Yulia Kreynina; Kathryn Howells; Sophie Wildsmith; Hannah Dry; Ana Nunes; Jyoti Mayadev
• Keywords: Durvalumab; Clinical endpoint; Chemoradiotherapy

<h3>Objectives</h3> In locally-advanced cervical cancer (LACC), platinum-based chemoradiotherapy (CRT) has been the standard- of-care treatment for &gt;20 years. CALLA is first global Phase 3 study evaluating immune checkpoint inhibition (durvalumab) versus placebo in combination with and following CRT LACC (NCT03830866). <h3>Methods</h3> Newly-diagnosed, untreated patients (FIGO 2009 stages IB2-IIB node positive, IIIA-IVA any status) were randomized 1:1 to durvalumab (1500 mg IV) or Q4W, a total of up 24 months, CRT. comprised concurrent weekly IV cisplatin EBRT brachytherapy. RT quality was monitored, variations evaluated clinical significance. The primary endpoint PFS; secondary endpoints include OS, objective response rate, local/distant disease progression incidence, safety. <h3>Results</h3> 770 (N=385 per arm) at 120 sites 15 countries. Median age 49 years; median follow-up 18.5 months. Durvalumab+CRT did not show statistically significant improvement PFS vs placebo+CRT (HR 0.84 [95% CI, 0.65–1.08]; P=0.174); there no detriment although data immature formally tested. Adverse events grade 3–4 occurred 51.7% 51.0% durvalumab+CRT arms, respectively; 12.5% 9.6% discontinued due AEs possibly related drug. <h3>Conclusions</h3> Durvalumab significantly improve LACC. Safety generally comparable alone, new unexpected toxicity. Funding: AstraZeneca.