Dataset Information

Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer.

ABSTRACT:

Background

There is a lack of data exploring the use and optimal timing of immunotherapy and chemoradiation therapy (CRT) in node-positive cervical cancer. Further translational research into mechanisms of response and resistance to immunotherapy in advanced cervical cancer is warranted.

Primary objectives

To determine if sequencing of atezolizumab and CRT result in differential immune activation, as determined by clonal expansion of T cell receptor beta (TCRB) repertoires in peripheral blood on day 21.

Study hypothesis

There is a difference for clonal expansion of T cell receptor beta repertoires in the peripheral blood at day 21 between the priming and concurrent atezolizumab and CRT in Arm A vs the concurrent atezolizumab and CRT in Arm B.

Trial design

Locally advanced cervical cancer patients with lymph node-positive disease will be randomized on this open-label, randomized trial with two experimental arms. Arm A will get one dose of atezolizumab prior to cisplatin CRT, and then two subsequent doses of atezolizumab during the CRT, and Arm B will get three doses during CRT. Patients will be followed for 2 years to assess outcomes.

Major inclusion/exclusion criteria

Patients must have histologically confirmed, newly diagnosed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): FIGO 2009 clinical stages IB2/IIA with positive para-aortic nodes, or FIGO 2009 clinical stages IIB/IIIB/IVA with positive pelvic or para-aortic lymph nodes. Exclusion criteria include those who had a prior hysterectomy or lymph node dissection.

Primary endpoints

Clonal expansion of TCRB) repertoires in peripheral blood on day 21.

Sample size

The sample size will be 40 patients.

Estimated dates for completing accrual and presenting results

We estimate accrual to finish by the summer of 2020 with presentation of results to follow in 2021.

Trial registration

NCT03738228.

SUBMITTER: Mayadev J

PROVIDER: S-EPMC7310564 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer.

Mayadev Jyoti J Zamarin Dmitriy D Deng Wei W Lankes Heather H O'Cearbhaill Roisin R Aghajanian Carol A CA Schilder Russell R

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 20191222 5

<h4>Background</h4>There is a lack of data exploring the use and optimal timing of immunotherapy and chemoradiation therapy (CRT) in node-positive cervical cancer. Further translational research into mechanisms of response and resistance to immunotherapy in advanced cervical cancer is warranted.<h4>Primary objectives</h4>To determine if sequencing of atezolizumab and CRT result in differential immune activation, as determined by clonal expansion of T cell receptor beta (TCRB) repertoires in peri ...[more]

PMID: 31871115

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Project description:ImportanceThe KEYNOTE-A18 trial demonstrated that adding concurrent and adjuvant pembrolizumab to chemoradiotherapy and brachytherapy significantly improved survival in patients with newly diagnosed, locally advanced cervical cancer. However, considering the annual global incidence of 660 000 cases of cervical cancer, including 13 820 in the US in 2024, incorporating this regimen into the standard of care could have substantial health care economic implications for both patients and the health care system.ObjectiveTo determine the cost-effectiveness of adding pembrolizumab to the first-line treatment of newly diagnosed, locally advanced cervical cancer.Design, setting, and participantsThis economic evaluation created a Markov model simulating 50-year outcomes to evaluate cost-effectiveness from the payer perspective for patients receiving either pembrolizumab or placebo in addition to chemoradiotherapy plus brachytherapy. Probabilities, including disease progression, survival, and treatment-related toxic effects, were derived from KEYNOTE-A18 clinical trial data in patients with newly diagnosed, locally advanced cervical cancer. Costs and health utilities were obtained from published literature; 1-way, 3-way, and probabilistic sensitivity analyses were used to assess model uncertainty. Data analyses were conducted from April to November 2024.ExposurePembrolizumab.Main outcomes and measuresCosts, measured in 2024 US dollars, and effectiveness, measured in quality-adjusted life-years (QALYs) were used to calculate an incremental cost-effectiveness ratio (ICER). A willingness-to-pay threshold of $100 000 per QALY was chosen, below which pembrolizumab would be considered cost-effective.ResultsKEYNOTE-A18 enrolled 1060 patients (529 in pembrolizumab group, 531 in placebo group). The median age was 50 years. Pembrolizumab increased costs by $257 000 and effectiveness by 1.40 QALYs, yielding an incremental cost-effectiveness ratio of $183 400 per QALY. The addition of pembrolizumab became cost-effective if its monthly cost was decreased from $16 990 to $9190 (a 45.6% reduction) or its maximum duration of 24 months was decreased to 10 months. The model was insensitive to assumptions about treatment-related toxic effects, progression-free survival, and overall survival. Probabilistic sensitivity analysis indicated that at a willingness-to-pay threshold of $100 000 per QALY, the addition of pembrolizumab was cost-effective 37.3% of the time.Conclusions and relevanceIn this economic evaluation of adding concurrent and adjuvant pembrolizumab to first-line treatment of newly diagnosed, locally advanced cervical cancer, this regimen was not cost-effective at current prices despite data demonstrating improved survival with this regimen.

Dataset Information

Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer.

Background

Primary objectives

Study hypothesis

Trial design

Major inclusion/exclusion criteria

Primary endpoints

Sample size

Estimated dates for completing accrual and presenting results

Trial registration

Publications

Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer.

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