CALLA: Efficacy and safety of durvalumab with and following concurrent chemoradiotherapy (CCRT) versus CCRT alone in women with locally advanced cervical cancer: A phase III, randomized, double-blind, multicenter study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5597-TPS5597 ◽  
Author(s):  
Bradley J. Monk ◽  
Jyoti Mayadev ◽  
Ana T Nunes ◽  
Alicja Dabrowska Brown ◽  
Michelle Marcovitz ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Locally Advanced ◽  
Figo Stage ◽  
Stage Iii ◽  
Disease Stage ◽  
Advanced Cervical Cancer ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer ◽  
Eortc Qlq

TPS5597 Background: CCRT is the standard of care for locally advanced cervical cancer. CCRT with PD-1/PD-L1 pathway blockade may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance. This Phase 3, randomized, multicenter, international, double-blind, placebo-controlled study is designed to determine the efficacy and safety of durvalumab with and following CCRT vs. CCRT alone in women with locally advanced cervical cancer (NCT03830866). Methods: The study will enroll immunotherapy-naïve adult patients (pts) with histologically confirmed cervical adenocarcinoma or cervical squamous or adenosquamous carcinoma (FIGO Stages IB2-IIB with node [N] positive and IIIA-IVA with any N) and no prior definitive surgical, radiation, or systemic therapy for cervical cancer. Approximately 714 pts will be randomized 1:1 to receive either durvalumab (1500 mg intravenously [IV]) or placebo every 4 weeks for 96 weeks. All pts will receive CCRT to the pelvis or pelvis + para-aortic radiotherapy field (45 Gy), followed by image-guided brachytherapy with cisplatin (40 mg/m2) IV or carboplatin (AUC2) IV once weekly for 5 weeks (6th dose optional). Randomization will be stratified by disease stage (FIGO Stage < III and N positive, FIGO Stage ≥III and N negative, or FIGO Stage ≥III and N positive) and region (US, Canada, EU, South Korea, and Japan vs. rest of the world). The primary endpoint is progression-free survival (assessed by investigator per RECIST v1.1 or histopathologic confirmation of local tumor progression). Secondary endpoints are overall survival, objective response and complete response (CR) rates, duration of response in pts with CR, incidence of local or distant disease progression or secondary malignancy, disease-related symptoms, and health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-CX24). Pharmacokinetics, immunogenicity, and safety of durvalumab will also be assessed. Pt enrollment is ongoing. Clinical trial information: NCT03830866.

scholarly journals CALLA: Efficacy and safety of concurrent and adjuvant durvalumab with chemoradiotherapy versus chemoradiotherapy alone in women with locally advanced cervical cancer: a phase III, randomized, double-blind, multicenter study

2020 ◽  
Vol 30 (7) ◽  
pp. 1065-1070
Author(s):  
Jyoti Mayadev ◽  
Ana T Nunes ◽  
Mary Li ◽  
Michelle Marcovitz ◽  
Mark C Lanasa ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Cervical Cancer ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer ◽  
To Receive

BackgroundConcurrent chemoradiotherapy is the standard of care for locally advanced cervical cancer. Concurrent chemoradiotherapy with programmed blockade of the cell death-1/programmed cell death-ligand 1 pathway may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance.Primary ObjectiveThe CALLA trial is designed to determine the efficacy and safety of the programmed cell death-ligand 1 blocking antibody, durvalumab, with and following concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in women with locally advanced cervical cancer.Study HypothesisDurvalumab concurrent with and following concurrent chemoradiotherapy will improve progression-free survival in patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IVA cervical cancer compared with concurrent chemoradiotherapy alone.Trial DesignCALLA is a phase III, randomized, multicenter, international, double-blind, placebo-controlled study. Patients will be randomized 1:1 to receive either durvalumab (1500 mg intravenously (IV)) or placebo every 4 weeks for 24 cycles. All patients will receive external beam radiotherapy with cisplatin (40 mg/m2) IV or carboplatin (area under the curve 2) IV once a week for 5 weeks, followed by image-guided brachytherapy.Major Inclusion/Exclusion CriteriaThe study will enroll immunotherapy-naïve adult patients with histologically confirmed cervical adenocarcinoma, cervical squamous, or adenosquamous carcinoma FIGO 2009 stages IB2–IIB node positive and stage IIIA–IVA with any node stage. Patients will have had no prior definitive surgical, radiation, or systemic therapy for cervical cancer.Primary EndpointThe primary endpoint is progression-free survival (assessed by the investigator according to Response Evaluation Criteria in Solid Tumors v1.1, histopathological confirmation of local tumor progression or death).Sample SizeApproximately 714 patients will be randomized 1:1 to receive either durvalumab + concurrent chemoradiotherapy or placebo + concurrent chemoradiotherapy.Estimated Dates for Completing Accrual and Presenting ResultsPatient enrollment is continuing globally with an estimated completion date of April 2024.Trial RegistrationNCT03830866.

scholarly journals Standard Chemoradiation and Conventional Brachytherapy for Locally Advanced Cervical Cancer: Is It Still Applicable in the Era of Magnetic Resonance–Based Brachytherapy?

2018 ◽  
pp. 1-9
Author(s):  
Prachi Mittal ◽  
Supriya Chopra ◽  
Sidharth Pant ◽  
Umesh Mahantshetty ◽  
Reena Engineer ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Cervical Cancer ◽  
Magnetic Resonance ◽  
Locally Advanced ◽  
Stage Iii ◽  
Advanced Cervical Cancer ◽  
X Ray ◽  
Locally Advanced Cervical Cancer ◽  
Level I ◽  
The Impact

Purpose Recent guidelines recommend magnetic resonance imaging–based brachytherapy (MRBT) for locally advanced cervical cancer. However, its implementation is challenging within the developing world. This article reports the outcomes of patients with locally advanced cervical cancer treated with chemoradiation and point A–based brachytherapy (BT) using x-ray– or computed tomography–based planning. Methods Patients treated between January 2014 and December 2015 were included. Patients underwent x-ray– or computed tomography–based BT planning with an aim to deliver equivalent doses in 2 Gy (EQD2) > 84 Gy10 to point A while minimizing maximum dose received by rectum or bladder to a point or 2 cc volume to < 75 Gy EQD2 and < 90 Gy EQD2, respectively. The impact of known prognostic factors was evaluated. Results A total of 339 patients were evaluated. Median age was 52 (32 to 81) years; 52% of patients had stage IB2 to IIB and 48% had stage III to IVA disease. There was 85% compliance with chemoradiation, and 87% of patients received four or more cycles. Median point A dose was 84 (64.8 to 89.7) Gy. The median rectal and bladder doses were 73.5 (69.6 to 78.4) Gy3 and 83 (73.2 to 90.0) Gy3, respectively. At a median follow-up of 28 (4 to 45) months, the 3-year local, disease-free, and overall survival for stage IB to IIB disease was 94.1%, 83.3%, and 82.7%, respectively. The corresponding rates for stage III to IVA were 85.1%, 60.7%, and 69.6%. Grade III to IV proctitis and cystitis were observed in 4.7% and 0% of patients, respectively. Conclusion This audit demonstrates good 3-year outcomes that are comparable to published MRBT series. Conventional BT with selective use of interstitial needles and MRBT should continue as standard procedures until level-I evidence for MRBT becomes available.

Concurrent chemoradiotherapy for locally advanced cervical cancer: Analysis of a single institutional 10-year experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16056-16056
Author(s):  
Y. Aoki ◽  
Y. Nagai ◽  
T. Toita ◽  
M. Hirakawa ◽  
M. Toma ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Late Complications ◽  
Disease Stage ◽  
Tumor Diameter ◽  
Advanced Cervical Cancer ◽  
Free Survival ◽  
Locally Advanced Cervical Cancer ◽  
Stage Ib

16056 Background: The purpose of this study was to report the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for the locally advanced cervical cancer in our institute. Methods: We retrospectively reviewed 147 patients (stage Ib: 9, II: 82, III: 80, and IVa: 7) with squamous cell carcinoma of the cervix treated with CCRT. Cisplatin (20mg/m2/day) was administered for 5 days every 3 weeks for a median of three courses (range: 1–5 courses) during radiotherapy (RT). The patients with paraaortic and/or common iliac lymphadenopathy were excluded. RT consisted of pelvic external beam RT (EBRT) with 40Gy/20 fractions followed by high-dose rate brachytherapy (HDR-BT) with 18Gy/3 fractions and pelvic EBRT with 10Gy/5 fractions using a midline block. Late complications were graded by the RTOG/EORTC criteria. Results: The 5-year actuarial overall survival (OS), disease-free survival (DFS), and pelvic relapse-free survival were 78.5%, 70.7%, and 78.0%, respectively. The 5-year OS by the disease stage was as follows: stage Ib 100%, II 82.0%, III 62.3%, and IVa 35.7%. Multivariate analysis identified pelvic lymphadenopathy, tumor diameter > 7cm, and pretreatment hemoglobin < 9.0g/dl as an independent prognostic factor for both OS and DFS. Only one patient suffered from grade 3 enterocolitis, but no grade 4 complication developed. Conclusions: Our experience suggests that CCRT using HDR-BT for locally advanced cervical cancer could achieve favorable local control without suffering from severe late complications. No significant financial relationships to disclose.

A new marker based on risk stratification of human papillomavirus DNA and tumor size to predict survival of locally advanced cervical cancer

2019 ◽  
Vol 29 (3) ◽  
pp. 459-465 ◽  
Author(s):  
Yecai Huang ◽  
Qiao He ◽  
Ke Xu ◽  
Jie Zhou ◽  
Jun Yin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Risk Stratification ◽  
Tumor Size ◽  
Locally Advanced ◽  
Figo Stage ◽  
Advanced Cervical Cancer ◽  
Hpv Dna ◽  
Locally Advanced Cervical Cancer ◽  
Advanced Cervical Carcinoma

ObjectiveTo assess the prognostic value of human papillomavirus (HPV) viral load in locally advanced cervical carcinoma treated with radical concurrent chemoradiotherapy.MethodsFrom January 2012 to October 2013, a total of 246 locally advanced cervical carcinoma patients were included in this retrospective study. HPV DNA status was tested by Hybrid Capture 2 assay. Tumor size was measured on T2WI. All the patients in the study received concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy and three-dimensional brachytherapy. Survival rate was calculated by the Kaplan-Meier method, and a log-rank test was used to compare the survival. Multivariate analysis employed the Cox regression model.ResultsThe median follow-up time was 52 months. The median value of HPV DNA was 163.13 relative light unit/cut-off (RLU/CO) (range 1.65–2162.62 RLU/CO). The 5-year overall survival, distant metastasis-free survival of patients in the low HPV DNA group (HPV DNA ≤ 163.13 RLU/CO) and the high HPV DNA group (HPV DNA > 163.13 RLU/CO) were 46.3 % vs 58.5 % (p = 0.009) and 65.9 % vs 75.6% (p = 0.003), respectively. Multivariate analysis showed that the HPV DNA, tumor size, and International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for overall survival and distant metastasis-free survival. We choose the tumor size and HPV DNA as the risk stratification factors to build a new prediction marker which can better predict overall survival for locally advanced cervical cancer than can the FIGO stage.ConclusionsHPV DNA may be a useful biomarker for locally advanced cervical cancer. Low HPV load predicts a worse survival. The new marker based on risk stratification by combining HPV DNA and tumor size is better associated with overall survival of locally advanced cervical cancer treated with concurrent chemoradiotherapy.

ENGOT-cx11/KEYNOTE-A18: A phase III, randomized, double-blind study of pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6096-TPS6096
Author(s):  
Domenica Lorusso ◽  
Nicoletta Colombo ◽  
Robert L. Coleman ◽  
Leslie M. Randall ◽  
Linda R. Duska ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
External Beam Radiotherapy ◽  
Locally Advanced ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind Study ◽  
Advanced Cervical Cancer ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer

TPS6096 Background: High-risk locally advanced cervical cancer has a poor prognosis, and more than half of patients recur in 2 y. External beam radiotherapy (EBRT) with concurrent chemotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer. The immunostimulatory activity of the PD-1 inhibitor pembrolizumab (pembro) may be enhanced by concurrent chemoradiotherapy (CRT). After the KEYNOTE-158 study, in which pembro showed durable antitumor activity, pembro monotherapy was approved for patients with PD-L1–positive recurrent or metastatic cervical cancer who progressed during or after chemotherapy. ENGOT-cx11/KEYNOTE-A18 (NCT04221945) is a phase III, randomized, placebo-controlled study evaluating pembro with concurrent CRT for the treatment of locally advanced cervical cancer. Methods: Approximately 980 patients with high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA), locally advanced, histologically confirmed cervical cancer who have not received systemic therapy, immunotherapy, definitive surgery, or radiation will be randomized 1:1 to receive either 5 cycles of pembro 200 mg every 3 wk (Q3W) + CRT followed by 15 cycles of pembro 400 mg Q6W or 5 cycles of placebo Q3W + CRT followed by 15 cycles of placebo Q6W. The CRT regimen includes 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT followed by brachytherapy. Randomization is stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cancer stage at screening (stage IB2-IIB vs III-IVA), and planned total radiotherapy dose. Treatment will continue until the patient has received 20 cycles of pembro (5 cycles 200 mg Q3W, 15 cycles 400 mg Q6W) vs placebo (~2 y) or until disease progression, unacceptable toxicity, or withdrawal. Primary endpoints are PFS per RECIST v1.1 by blinded independent central review and OS. Secondary endpoints are PFS at 2 y, OS at 3 y, complete response at 12 wk, ORR, PFS and OS in PD-L1–positive patients, EORTC QLQ-C30 and QLQ-CX24, and safety. Enrollment is ongoing. Clinical trial information: NCT04221945.

Prognostic value of tumor parameters measured by MRI in cervical cancer patients receiving CCRT.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17027-e17027
Author(s):  
Chang Sun ◽  
Shun Lu ◽  
Ran Lin Wang ◽  
Hanyi Zhang ◽  
Mingyu Tan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Multivariate Analysis ◽  
Tumor Volume ◽  
Locally Advanced ◽  
Reduction Rate ◽  
Figo Stage ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer ◽  
Tumor Volume Reduction

e17027 Background: This study aimed to evaluate the response of solid tumors after the completion of external beam radiotherapy (EBRT) and investigate the prognostic value of tumor parameters such as tumor volume and size (TV & TS) and tumor volume reduction rate (TVRR) early during the treatment in local advanced cervical cancer patients. Methods: We retrospectively reviewed 310 Chinese patients with locally advanced cervical cancer. They were all received concurrent chemoradiotherapy (CCRT) during the treatment based on intensity modulated radiotherapy (IMRT). Clinical data at the time of diagnosis, including FIGO stage, TV and TS were measured by pelvic magnetic resonance imaging (MRI) before and after EBRT were available. Information about distant metastasis, relapse and date of death was also collected, with a follow-up until Aug 2018. Youden index was used to identify the optimal cut-off point of continuous tumor parameters and divide patients into subgroups. Prognostic factors (age, FIGO stage, RT dose, pre-RT TS and TV, mid-RT TS and TV, TVRR) were using the log-rank test and Cox regression models to analyze the association between predictors and time-to-event outcomes. Results: The median follow-up time was 50 months. In univariate analysis, the FIGO stage, TVRR, TV and TS were associated with overall survival rate. Interestingly, the group of higher TVRR showed a better OS, PFS and LRFS than the group of lower TVRR ( P <0.05). Moreover, the groups of lower TV and TS showed better OS, PFS and LRFS than the higher groups, respectively. In the OS-related multivariate analysis, the mid-RT TV remained statistically significant after adjustment for age and FIGO stage ( P < 0.05). In the PFS-related multivariate analysis, the tumor volume reduction rate (TVRR) remained statistically significant after adjustment for age, FIGO stage, TS, and TV ( P <0.05). In addition, in the LRFS-related multivariate analysis, TVRR also remained statistically significant after adjustment for age, FIGO stage, TS, and TV ( P <0.05). Conclusions: Our results confirmed that tumor parameters including TS, TV and TVRR, measured before the completion of CCRT, are valuable prognostic factors in patients with locally advanced cervical cancer.

MRI-based radiomics: promise for locally advanced cervical cancer treated with a tailored integrated therapeutic approach

2021 ◽  
pp. 030089162110142
Author(s):  
Concetta Laliscia ◽  
Angiolo Gadducci ◽  
Roberto Mattioni ◽  
Francesca Orlandi ◽  
Sabina Giusti ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Figo Stage ◽  
High Dose ◽  
Advanced Cervical Cancer ◽  
Primary Tumor Site ◽  
Locally Advanced Cervical Cancer ◽  
Sequential Boost

Objective: To assess prognostic factors by analyzing clinical and radiomic data of patients with locally advanced cervical cancer (LACC) treated with definitive concurrent cisplatin-based chemoradiotherapy (CCRT) using magnetic resonance imaging (MRI). Methods: We analyzed radiomic features from MRI in 60 women with FIGO (International Federation of Gynecology and Obstetrics) stage IB2–IVA cervical cancer who underwent definitive CCRT 45–50.4 Gy (in 25–28 fractions). Thirty-nine (65.0%) received EBRT sequential boost (4–20 Gy) on primary tumor site and 56 (93.3%) received high-dose-rate brachytherapy boost (6–28 Gy) (daily fractions of 5–7 Gy). Moreover, 71.7% of patients received dose-dense neoadjuvant chemotherapy for 6 cycles. The gross tumor volume was defined on T2-weighted sequences and 29 features were extracted from each MRI performed before and after CCRT, using dedicated software, and their prognostic value was correlated with clinical information. Results: In univariate analysis, age ⩾60 years and FIGO stage IB2–IIB had significantly better progression-free survival (PFS) ( p = 0.022 and p = 0.009, respectively). There was a trend for significance for worse overall survival (OS) in patients with positive nodes ( p = 0.062). In multivariate analysis, only age ⩾60 years and FIGO stage IB2–IIB reached significantly better PFS ( p = 0.020 and p = 0.053, respectively). In radiomic dataset, in multivariate analysis, pregray level p75 was significantly associated with PFS ( p = 0.047), pre-D3D value with OS ( p = 0.049), and preinformation measure of correlation value with local control ( p = 0.031). Conclusion: The combination of clinical and radiomics features can provide information to predict behavior and prognosis of LACC and to make more accurate treatment decisions.

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