• For the first time, an immunotherapy treatment achieves results in patients with neuroendocrine tumours, increasing survival at 9 months from 13% to 36%
  • In turn, the results of the KEYNOTE-177 study have shown how treatment with pembrolizumab improves quality of life in colorectal cancer patients with microsatellite instability, in addition to improving their survival

Barcelona, 21 September 2020.– In recent years, immunotherapy has been one of the cancer treatment strategies that has been achieving the most promising results. From being merely a promising route, it is increasing becoming a reality. At the annual ESMO congress, the progress made in this field over the last year occupied an important place, which should come as no surprise, with a prominent role for the investigators at the Vall d’Hebron Institute of Oncology (VHIO).

Immunotherapy in neuroendocrine tumours

This is the case, for example, of the investigation led by Dr Jaume Capdevila, an investigator in the VHIO Gastrointestinal and Endocrine Tumours Group and chair of the Spanish Neuroendocrine and Endocrine Tumours Group. In their DUNE study, a phase II clinical trial, they sought to evaluate the efficacy of a combination therapy with two immunotherapy drugs in patients with advanced neuroendocrine neoplasms of various origins. “We established four different cohorts according to the origin of these neoplasms. Thus, we had those whose origin was the lung, those with a gastrointestinal and pancreatic origins, and highly aggressive grade III neuroendocrine tumours”, explains Dr Capdevila.

The combination tested was that of durvalumab and tremelimumab. Durvalumab is a type of monoclonal antibody that binds to the PD-L1 protein, acting as an immune checkpoint inhibitor, thus helping immune cells to better kill cancer cells. This drug has been successful in treating lung and bladder cancer. In turn, tremelimumab binds to another protein, in this case CTLA-4, which is found on the surface of T cells. In this case, it is an immunomodulatory drug that stimulates the immune system to attack cancer cells. Its use is also approved for the treatment of lung cancer, as well as melanoma and mesothelioma.

The importance of this study lay in the fact that, to date, few studies have been conducted to evaluate the efficacy of immunotherapy in neuroendocrine tumours. “Furthermore, in the few that have been carried out, the results obtained have not been very positive; immunotherapy does not seem to be working for this type of cancer”, adds Dr Jaume Capdevila, who also points out how the best results were obtained in cohort 4, that of patients with grade III neuroendocrine tumors.

“In these patients, it seems that it may be more effective, since we have managed to exceed the expectations we had when we started the trial, and the survival of patients has improved significantly”, Dr Capdevila goes on to explain. Thus it has been observed how, at 9 months, the survival of these patients increased from 13% to 36%, and that even after one year the patient survival rate was 30%. “We have to take into account that these are patients with a very poor prognosis, in whom chemotherapy had already ceased to have an effect, and who currently have no treatment option, so this study opens the door to a new treatment option, which will need to be confirmed in phase III studies”, adds Dr Jaume Capdevila.

Immunotherapy in colorectal cancer
The other immunotherapy-related study in which VHIO investigators have participated is the one that sought to evaluate the quality of life of patients with metastatic colorectal cancer with microsatellite instability who were receiving pembrolizumab monotherapy, compared to those treated with standard chemotherapy. This is a sub-analysis of the phase III KEYNOTE-177 trial, in which Dr Elena Élez, an investigator at the VHIO Gastrointestinal and Endocrine Tumors Group, participated. The results of this study were presented in the framework of a plenary session at the most recent ASCO congress.

Pembrolizumab is an antibody that binds to the PD-1 receptor, a negative regulator of T-cell activity involved in the control of T-cell immune responses. Thus, the response of these cells is enhanced, including the anti-tumour responses. “Results from this trial had previously been reported, in which it was demonstrated that pembrolizumab monotherapy treatment was able to improve both overall survival and disease progression-free survival in these patients, and it did so with fewer adverse effects. Now, we also know that they do so with an improved quality of life, and this points to a change in the standard of their treatment”, adds Dr Elena Élez.

Thus, according to the results that have been observed in this clinical trial, patients receiving pembrolizumab had reduced physical functional impairment and less fatigue than those receiving chemotherapy.

“Pembrolizumab is not without side effects. In some cases, such as abdominal pain or stoma care problems, they may be slightly more common than with chemotherapy. Nonetheless, they are still far fewer than those of chemotherapy, and are less limiting for patients”, points out Dr Elena Élez, who indicates that some of the effects of chemotherapy that most affect patients’ quality of life, such as hair loss, dry mouth, or skin disorders, do not occur when pembrolizumab is administered.