CALLA Trial: Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer: a randomized, double-blind, phase 3 trial

Type: Cervical Cancer

Section: Medical treatment for cervical cancer

Published: October 2024

The CALLA trial was a large, global study that started in 2018 and involved 770 women with locally advanced cervical cancer.
Background

Cervical cancer is a type of cancer that starts in the cervix, which is the lower part of the uterus. In recent years, doctors have explored different treatment methods to improve outcomes for women with cervical cancer. For locally advanced cervical cancer, the standard treatment involves a combination of chemotherapy and radiation therapy (CRT). This approach aims to shrink the tumor and kill cancer cells. However, newer treatments like immunotherapy have been gaining attention. The CALLA trial was set up to see if adding an immunotherapy drug called durvalumab to the standard CRT treatment would improve survival for women with locally advanced cervical cancer.


What is Durvalumab?

Durvalumab is a medicine used to treat a type of lung cancer called non-small cell lung cancer (NSCLC). It is used in adult patients with advanced cancer that cannot be removed by surgery but is not getting worse after treatment with radiation and platinum-based chemotherapy (medicines used to treat cancer). Durvalumab is used specifically when the tumour produces a protein known as PD-L1.


Mechanism of Action of Immunotherapy



The CALLA Trial

The CALLA trial was a large, global study that started in 2018 and involved 770 women with locally advanced cervical cancer. These women were split into two groups. One group received the standard treatment of chemotherapy and radiation therapy (CRT). The other group received CRT along with durvalumab.

The goal of the trial was to see if adding this immunotherapy would help women live longer without their cancer getting worse. The trial followed these women over time to track the success of the treatments.



Outcome

The results of the CALLA trial, released in 2023, showed that adding durvalumab did not significantly improve outcomes compared to the standard treatment. Here are the main findings:

• No Major Improvement in Cancer Control: Women who received durvalumab along with CRT did not show a significant reduction in cancer progression compared to those who only had CRT.


• Survival Rates Were Similar: Both groups had similar overall survival rates. Adding durvalumab did not make a clear difference in helping women live longer or preventing their cancer from returning.

Because the immunotherapy did not show a strong benefit, the trial did not change the standard treatment for locally advanced cervical cancer.


Conclusion

The CALLA trial explored whether adding the immunotherapy drug durvalumab to the standard treatment of chemotherapy and radiation could improve outcomes for women with locally advanced cervical cancer. Unfortunately, the results showed that it did not lead to better survival or a significant decrease in cancer recurrence.

Research like the CALLA trial is essential for exploring new treatments, even when the results don’t lead to immediate changes. It helps doctors better understand which treatments work best and which do not, guiding future advances in cancer care.

Reference:

1. Monk, B. J., Toita, T., Wu, X., Vázquez Limón, J. C., Tarnawski, R., Mandai, M., Shapira-Frommer, R., Mahantshetty, U., Del Pilar Estevez-Diz, M., Zhou, Q., Limaye, S., Godinez, F. J. R., Oppermann Kussler, C., Varga, S., Valdiviezo, N., Aoki, D., Leiva, M., Lee, J. Y., Sulay, R., Kreynina, Y., … Mayadev, J. (2023).

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial. The Lancet. Oncology, 24(12), 1334–1348. https://doi.org/10.1016/S1470-2045(23)00479-5


2. Mayadev, J., Nunes, A. T., Li, M., Marcovitz, M., Lanasa, M. C., & Monk, B. J. (2020). 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. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 30(7), 1065–1070. https://doi.org/10.1136/ijgc-2019-001135