NEW YORK — An immunotherapy-chemoradiotherapy (CRT) combination did not boost progression-free survival (PFS) in untreated, locally advanced cervical cancer, according to CALLA trial findings.
Newly diagnosed patients who received durvalumab (Imfinzi) plus standard CRT did not experience a statistically significant PFS improvement versus patients who received placebo plus CRT (hazard ratio 0.84, 95% CI 0.65-1.08, P=0.174), reported Bradley Monk, MD, of the University of Arizona School of Medicine in Phoenix.
While there was no detrimental effect on overall survival (OS) with the combo treatment, these data were immature and not formally tested, Monk warned in a presentation at the International Gynecologic Cancer Society annual meeting.
“We’ve got work to do in trying to cure more patients with locally advanced cervical cancer,” Monk stressed, adding that CALLA is the fifth randomized trial — following four studies done in head and neck cancer — that showed immunotherapy-CRT has yet to move on the needle on PFS in these disease states.
Finding superior treatments to CRT remains a challenge, he said. CRT has been the standard of care for patients with locally advanced cervical cancer for the last 20 years, and approximately 67% of low-risk patients who receive CRT remain progression free at 2 years, Monk added.
Immunotherapy represents a new treatment option for cervical cancer, and has shown good outcomes in the recurrent setting. CALLA is a global phase III trial comparing durvalumab-CRT to placebo-CRT. The trial enrolled patients with cervical adenocarcinoma or squamous carcinoma from 120 sites in 15 countries. Patients had FIGO stage IA-IIB disease and at least one positive node, or FIGO stage III-IVA disease and any nodal involvement. They were randomized 1:1 to durvalumab (1500 mg IV), or placebo, plus standard CRT for up to 2 years. CRT was comprised of weekly cisplatin with external-beam RT and brachytherapy.
The trial had 770 patients who were divided between the two study groups. Most patients had squamous carcinomas. Around 66% of patients had stage III or IVA cancer, and 64% had positive pelvic nodes. Patient median age was 49. The median follow up was 18.5 months.
Monk and colleagues reported that there was no improvement in local disease progression events (HR 1.06, 95% CI 0.69-1.63), although there was a trend towards improvement in distant disease progression events (HR 0.75, 95% CI 0.53-1.06), although this finding was not statistically significant.
Safety outcomes for durvalumab-CRT were comparable to placebo-CRT, with no new or unexpected toxicities, Monk said. Grade 3 and 4 adverse events (AEs) occurred in 51.7% of patients in the durvalumab-CRT group and 51% in the placebo-CRT group. Around 12.5% and 9.6%, respectively, discontinued treatment related to AEs, possibly tied to the study drug, he noted.
In a March 2022 press release, Monk emphasized that CALLA findings “will inform future strategies to improve treatment for patients with locally advanced cervical cancer.”
CALLA was funded by AstraZeneca. A co-author is a company employee.
Monk disclosed relationships with Agenus, Amgen, Akeso Biopharma, Aravive, Bayer, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Merck, Genentech/Roche, Genmab/Seattle Genetics, GOG Foundation, Gradalis, Immunogen, Iovance Biotherapeutics, Karyopharm Therapeutics, Mersana, Myriad Pharmaceuticals, Novocure, Pfizer, Puma Biotherapeutics, Regeneron, and Sorento Therapeutics.