Cervical cancer: more effective treatment with immunotherapy

The phase III study, involving more than 1000 women in 30 countries, showed a significant improvement in progression-free survival in women with locally advanced high-risk cervical cancer who received immunotherapy along with standard therapy with chemotherapy and radiotherapy.

These are the first results related to first-line treatment for newly diagnosed locally advanced cancers.

The addition of immunotherapy to standard chemo-radiotherapy treatment offers significant and clinically relevant improvements in the survival of women diagnosed with locally advanced, high-risk cervical cancer.

This is the encouraging result of a multicentre phase III study published in the Lancet journal created and coordinated by Domenica Lorusso – now Head of Gynaecological Oncology at Humanitas San Pio X and Full Professor at Humanitas University – while she was Head of Clinical Research Planning Unit at the Agostino Gemelli IRCCS University Polyclinic Foundation in Rome. Professor Giovanni Scambia, Director of the Operative Unit of Oncological Gynaecology at the Policlinico Universitario A. Gemelli IRCCS, Scientific Director of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Professor of Gynaecology and Obstetrics at the Università Cattolica, also took part in the study.

Cervical cancer is the fourth most common cancer in women worldwide and the fourth leading cause of cancer death in women between the ages of 35 and 54.

The protocol involved the administration of pembrolizumab, an immune checkpoint inhibitor, along with a standard course of radiotherapy and concomitant chemotherapy, followed by a maintenance treatment with pembrolizumab alone. The results showed that the combination treatment with immunotherapy, when compared to standard treatment plus placebo, resulted in a 30% reduction in the risk of disease progression or death. This benefit was consistent in all patient subgroups, although it was more pronounced in cases where the disease was more advanced.

“This is an important milestone, since conventional treatment, which has been in use since 1999, has a limited efficacy, especially for patients with the locally advanced form of the disease,” says Prof. Domenica Lorusso. “Previous studies had already shown improvements with the use of pembrolizumab, either alone or in combination with chemotherapy regimens, but only in patients with metastatic or relapsing cervical cancer. This is the first time we are testing the treatment in the first-line, for newly diagnosed locally advanced cancers’.

The safety profile of pembrolizumab in combination with chemo-radiotherapy was consistent with those of the individual treatment components, thus presenting no cumulative risk effects.

Prof. Giovanni Scambia: ‘This is the first study to report a significant improvement in survival for locally advanced, high-risk cervical cancer. We believe that this data may pave the way for a new combined therapeutic approach – immunotherapy and chemo-radiotherapy – for this type of cancer’.

The clinical study

The study involved 1060 patients with newly diagnosed high-risk and locally advanced cervical cancer, enrolled at 176 centres in 30 countries worldwide between June 2020 and December 2022.

The patients were assigned to two double-blind groups (i.e. neither they nor the researchers knew which group they belonged to): a group of 529 patients who were given pembrolizumab in addition to chemo-radiotherapy treatment and a control group, with 531 patients, who were given a placebo in addition to standard treatment. Pembrolizumab (or placebo) was administered both during and at the end of the chemo-radiotherapy cycles as maintenance treatment.

According to the study results, two years after treatment, pembrolizumab reduced the risk of disease progression or death by 30%.

The effects of the treatment were seen as early as the first radiographic evaluation and continued over time. Therefore, the researchers believe that the difference between the two groups in terms of efficacy, and thus the improvement conferred by pembrolizumab, may increase as the follow-up continues.

Recently data from the first Phase 3 study was also released, indicating a statistically significant and clinically relevant improvement in the overall survival of patients treated with this treatment approach.

The effect of the monoclonal antibody that disrupts the immune system

Pembrolizumab is a monoclonal antibody that inhibits the activation of a T-cell surface protein called PD-1. Inhibiting this protein during the treatment of a tumour is important because PD-1 works like a brake: when it is stimulated it weakens the action of the T-cells and thus the entire immune response, favouring tumour proliferation. It is no coincidence that many tumour cells express proteins on their membranes that bind to PD-1 and activate it, thus preventing T cells from recognising and attacking the tumour. By inhibiting PD-1, pembrolizumab thus interferes with one of the mechanisms the tumour uses to protect itself from an attack by the immune system.

Pembrolizumab belongs to the family of immune checkpoint inhibitors, whose discovery won the 2018 Nobel Prize in Medicine. Their introduction for clinical use has already revolutionised the treatment of many types of cancer, although research continues: there are numerous ongoing clinical trials testing the efficacy of this class of drugs for new types of tumours or in new combinations with standard treatments, with the aim of improving the efficacy of therapies and making cancer more and more treatable.

Cervical cancer

Cervical cancer is the second most frequent gynaecological cancer among women, after endometrial cancer, with an estimated 2,500 new diagnoses (1.3% of all female cancers) in 2022. Cervical cancer in the early stages generally has no symptoms. When symptoms occur, however, they are common to many diseases of the female genital tract, which makes it difficult to obtain an early diagnosis.

Cervical cancer is caused in 97% of cases by a human papillomavirus (HPV) infection, which is transmitted sexually. This cancer can be prevented by a free HPV vaccination offered to men and women aged 12 to 26, and by regular screenings with a Pap test or HPV-DNA test. The Pap test should be performed every three years from the age of 25 (indications change in the event of a positive result) whereas the HPV test every five years from the age of 30-35.


Humanitas is a highly specialized Hospital, Research and Teaching Center. Built around centers for the prevention and treatment of cancer, cardiovascular, neurological and orthopedic disease – together with an Ophthalmic Center and a Fertility Center – Humanitas also operates a highly specialised Emergency Department.