For patients with persistent/recurrent/metastatic cervical or endometrial cancer who can’t be treated with curative surgery or radiotherapy, there has been a need for treatment options for decades, with little progress made.

Cervical cancer is the third-most common cancer type in women. The 5-year survival rate for women with cervical cancer that has spread, is only 17%. For women with recurrent disease, prognosis is even worse. Endometrial cancer is the most frequent gynaecological cancer. When endometrial cancer is diagnosed in late stages or is very aggressive, the chance of recurrence is very high. The prognosis for patients with recurrent disease is dismal because of the lack of treatment options.  

Currently available treatments for these patients are scarce and often accompanied by considerable side effects. Therefore, effective and less toxic treatments are urgently needed for patients with refractory or recurrent endometrial or cervical cancer.

To overcome this need, the Anticancer Fund has supported the PRIMMO study, a phase II trial in patients with pre-treated persistent/recurrent/metastatic cervical or endometrial cancer.

Treatment options that can improve survival while maintaining quality of life are urgently needed.

This publication reports the results of the PRIMMO study:

Over the last decades, treatments that revolve around immune checkpoints became the forefront of immune-oncology. Immune checkpoints make sure that we don’t get attacked by our own immune system. Tumours can make use of these immune checkpoints to avoid being attacked and thus eliminated. Immune checkpoint inhibitors prevent the activation of these immune checkpoints in tumour cells, overruling the suppression of the immune system that was highjacked by the tumour.

Unfortunately, less than 20% of cervical and endometrial cancer patients respond to treatment with immune checkpoint inhibitors. The reason for this may be that these types of tumours and their surroundings suppress the immune system in other ways, which might hamper effectiveness of the treatment. Because a tumour consists of a complex composition of different cells, a combination of treatments is more likely to destroy it efficiently.

The PRIMMO trial aimed to improve the treatment for cervical and endometrial cancer and uterine sarcoma patients by adding a combination of 6 therapies to the immune checkpoint inhibitor, which could collectively enable the immune system to kill the tumour.

Unfortunately, the results of the trial were not as hoped. While the treatment combination used showed promising results in earlier laboratory research, it did not meet the expectations in the clinical trial: combining all 7 therapies didn't improve the efficacy in the study patients, compared to treatment with the immune checkpoint inhibitor alone, although the investigators find that some difficult-to-treat patients may have derived benefit from the treatment with durable responses in difficult-to-treat patients.

Further research is vital to provide better treatment options for patients with these gynecological tumours.