Durvalumab given concurrently with chemoradiation was not found to significantly improve progression-free survival vs chemoradiation alone in patients with locally advanced cervical cancer, missing the primary end point of the phase 3 CALLA trial.
Durvalumab (Imfinzi) given concurrently with chemoradiation was not found to significantly improve progression-free survival (PFS) vs chemoradiation alone in patients with locally advanced cervical cancer, missing the primary end point of the phase 3 CALLA trial (NCT03830866).1
The safety and tolerability of the approach was found to be consistent between the 2 arms, with no new safety signals observed.
Data from the trial are expected to be shared at an upcoming medical conference.
“While today’s results were not statistically significant, they underscore the need for further evaluation of novel therapeutic options and will inform future strategies to improve treatment for patients with locally advanced cervical cancer,” Bradley Monk, MD, FACOG, FACS, professor at the University of Arizona College of Medicine and principal investigator in the CALLA trial, stated in a press release.
The double-blind, placebo-controlled, multicenter trial enrolled patients with histologically confirmed cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma with FIGO 2009 stage IB2 to IIB, node-positive or FIGO 2009 stage IIIA to IVA with any N stage, or N staging either by surgical confirmation or imaging per RECIST v1.1 criteria.2
Patients needed to be at least 18 years of age, have a World Health Organization or ECOG performance status of 0 or 1, and at least 1 lesion that qualifies as a RECIST v1.1 tumor lesion not previously irradiated at baseline assessment. Patients could not have previously received chemotherapy or radiotherapy for cervical cancer and they needed to be immunotherapy naïve.
If patients had neuroendocrine cervical cancer with small cell histology, had intention to administer a fertility-sparing treatment regimen, previously underwent hysterectomy or had intent to have hysterectomy, had evidence of metastatic disease per RECIST v1.1 criteria, or a history of another primary malignancy, active primary immunodeficiency, documented autoimmune or inflammatory disorders, or allogeneic organ transplantation, they were excluded.
Patients were randomized 1:1 to receive durvalumab at 1500 mg every 4 weeks (n = 357) or placebo with concurrent chemoradiation to the pelvis or pelvis plus para-aortic radiotherapy field, at a prescription dose of 45 Gy to the pelvis in 25 fractions at 1.7 Gy/fraction with a parametrial boost and an optional lymph node boost, given once daily and 5 fractions per week (n = 357).
This was followed by image-guided brachytherapy at 27.5 Gy to 30 Gy for high-dose rate and 35 Gy to 40 Gy for low- or pulsed-dose rate in addition to concurrent cisplatin at 40 mg/m2 or carboplatin at area under the curve 2 once weekly for 5 weeks, with continuation to the sixth week per investigator discretion.
Patients were stratified based on disease stage (stage <III and node positive, stage ≥IIII and node negative, or stage ≥III and node positive), region (United States, Canada, European Union, South Korea, and Japan vs rest of the world).
The primary end point of the trial was PFS, and a key secondary end point was overall survival. Other key secondary end points included PFS in PD-L1–positive patients, objective response rate, complete response (CR) rate, duration of response in patients with a CR, health-related quality of life, pharmacokinetics, immunogenicity, safety, and incidence of local progression, distant disease progression, and secondary malignancy as the first documented progression event.
Other exploratory end points included PFS at 3 years, candidate markers likely to correlate with clinical benefit, and patient-reported outcomes.
“CALLA tested a novel immunotherapy approach in locally advanced cervical cancer, a devastating and complex disease where many patients progress following available treatments,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, added in the press release. “While the results were not what we hoped for, insights from the trial will advance our understanding and application of immunotherapy across our broad clinical development programme, exploring the benefits of [durvalumab] in many tumor types.”