Durvalumab Plus Chemoradiotherapy Does Not Extend PFS in Locally Advanced Cervical Cancer

Bradley Monk, MD, FACOG, FACS

Durvalumab (Imfinzi) administered concurrently with chemoradiotherapy (CRT) did not demonstrate a statistically significant improvement in progression-free survival (PFS) compared with CRT alone in patients with locally advanced cervical cancer, missing the primary end point of the phase 3 CALLA study, according to an announcement by AstraZeneca.¹

Despite the efficacy result, the safety and tolerability of durvalumab in the study were consistent between the 2 treatment arms with no unexpected safety findings. The data will be presented at an upcoming medical meeting.

“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,” said Bradley Monk, MD, FACOG, FACS, professor at the University of Arizona College of Medicine and principal investigator in the CALLA study, in a press release.

CALLA is a randomized, multicenter, double-blind, global study exploring durvalumab in combination with CRT and following CRT, compared with CRT alone in 700 patients with locally advanced cervical cancer.² The goal of the trial was to challenge the standard of care locally advanced cervical cancer using concurrent CRT with programmed blockade of the cell death-1/programmed cell death-ligand 1 pathway in an effort to promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, which may improve immune-mediated tumor surveillance.³

Durvalumab was administered via infusion every 4 weeks with cisplatin, carboplatin, and external beam radiation therapy (EBRT) plus brachytherapy in the experimental arm. Patients in the comparator arm were given placebo plus cisplatin, carboplatin, and BRT plus brachytherapy.²

Secondary end points assessed in the study included overall survival (OS), complete response rate, objective response rate, disease control rate, PFS rate at 3 years, PFS in the PD-L1-positive patients, and OS in the PD-L1-postiive patients.

Those included in the study were female age 18 years or older with documented evidence of evidence of cervical adenocarcinoma or squamous carcinoma FIGO stages IB2 to IIB node positive or FIGO IIIA-IVA any node, according to the 2008 criteria. All patients enrolled must no have received prior chemotherapy or radiotherapy for cervical cancer, have a World Health Organization and ECOG performance score of 0-1, and at least 1 target lesion per RECIST v1.1 criteria that was not previously irradiated.

Patients excluded from the study were those diagnosed with small cell histology or mucinous adenocarcinoma cervical cancer, and those with Intent to administer a fertility-sparing treatment regimen. In addition, patients who had undergone a previous hysterectomy, or have Evidence of metastatic disease per RECIST 1.1, history of allogeneic organ transplantation, active or prior documented autoimmune or inflammatory disorders, uncontrolled intercurrent illness, or history of another primary malignancy and active primary immunodeficiency were excluded from the study.

Analyses are ongoing at 118 locations in the United States, South America, Europe, and Asia.

“CALLA tested a novel immunotherapy approach in locally advanced cervical cancer, a devastating and complex disease where many patients progress following available treatments. 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 program, exploring the benefits of Imfinzi in many tumor types, said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the press release.¹

_REFERENCES:

_{1. Update on CALLA Phase III trial of concurrent use of Imfinzi and chemoradiotherapy in locally advanced cervical cancer. News release. AstraZeneca. March 24, 2022. Accessed March 28, 2022. https://bit.ly/37X414S}

_{2. Study of durvalumab with chemoradiotherapy for women with locally advanced cervical cancer (CALLA). Clinicaltrials.gov. Accessed March 28, 2022. https://bit.ly/3wJ2OZn}

_{3. Mayadev J, Nunes AT, Li M, et al. 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. Int J Gynecol Cancer. 2020;30(7):1065-1070. doi: 10.1136/ijgc-2019-001135.}