Just 15 years ago, the prognosis for a patient with metastatic melanoma was devastating: there was no way to stop the progression of this aggressive skin cancer and life expectancy was around six months. However, at the beginning of the last decade, the scientific community gave a knock on the table and began to change the course of this disease with the introduction of immunotherapy, which consisted of stimulating the body’s own defenses to help them destroy malignant cells. Today, the survival rate of a person with this same skin tumor can exceed 10 years.
Melanoma was the first stop in the therapeutic revolution that immunotherapy represented in oncology. Its excellent results encouraged its expansion into other tumors and it also ended up changing the prognosis in some types of lung, bladder and breast cancer, among others. After more than a decade in clinical practice, this innovative therapeutic approach, which is still in development and being increasingly refined, has achieved unusual survival rates in a handful of tumors: a study presented this weekend in Barcelona during the Congress of the European Society for Medical Oncology (ESMO) and published simultaneously in the journal New England Journal of Medicinereports on its long-term impact and reveals that almost half of patients with metastatic melanoma treated with immunotherapy survive without cancer 10 years later. Another study, presented at the same congress, also highlights how this type of drug increases survival in the most aggressive breast cancer, triple negative. The experts consulted assure that these data support the potential of immunotherapy in cancer, but admit that there are still pending tasks, such as fine-tuning the patients who will benefit most from this therapeutic strategy and exploring the combination with other drugs to optimize its results.
A 10-year follow-up study of patients treated with a combination of immune checkpoint inhibitors, a type of immunotherapy that removes the brakes that the tumor puts on the immune system to prevent its attack, has revealed that this therapeutic approach radically improved the prognosis of the disease and its effect persisted for several years. “The median survival for this population is now a little more than six years, and people who are free of cancer progression at three years have a high probability of remaining alive and disease-free at 10 years,” explains Jedd Wolchock, author of the study and oncologist at the NewYork-Presbyterian/Weill Cornell Medical Center, in a statement.
In addition to confirming the long-term survival data, the study also shed light on another of the unknowns that has been troubling oncologists: the long-term impact of these treatments, which are not free of side effects resulting from this intense stimulation of the immune system. Despite fears of potential health damage from these drugs, the research found no worrying signs of long-term toxicity.
The scientists also reported that when looking at melanoma survival and overall survival from other causes, over the long term, these lines diverge. That is, as they get older and older, melanoma survivors are more likely to die from other causes than from the cancer. “We can now say that half of the patients treated with this combination therapy will live 10 years or more without the worry of dying from metastatic melanoma,” Wolchock says.
Other studies were also presented at the ESMO congress showing how immunotherapy also improves survival in the most aggressive breast cancer (triple negative) and in muscle-invasive bladder cancer. Specifically, in breast cancer, research shows that, in the early stages, patients with triple negative tumours treated with a combination of immunotherapy and chemotherapy before surgery and who continue with immunotherapy after surgery, have a higher five-year survival rate (86.6%) than the study arm that received placebo (81.2%). “Immunotherapy helps to cure more patients and this is important data because at five years, survival increases significantly: out of every 100 patients, five respond thanks to having received immunotherapy; if we had not given it to them, they would not have been cured,” says Javier Cortés, co-author of this research and director of the International Breast Cancer Center in Barcelona. The oncologist admits that in breast cancer, the results are not expected to be as overwhelming as in melanoma, but, in any case, he maintains: “These are very important data because we are curing more and more patients.”
Caution in expectations
All of this research is a boost for immunotherapy in cancer. And although many oncologists are reluctant to say the word cure because they know how treacherous this disease can be, the authors of the melanoma research do point to it in the study: “The sustained benefit of immune checkpoint inhibitors observed during the long follow-up period in this trial highlights the potential for cure in patients with advanced melanoma who have a response to this type of treatment,” they say.
However, doctors continue to call for caution and, this Sunday, during the ESMO press conference on these advances, Jessica Hassel, an oncologist at the University Hospital of Heidelberg (Germany), asked to be “very careful” with the use of the word cure, especially in contexts where the disease is advanced (when it has spread to other parts of the body). “We prefer the word long-term control because there may be latent cells that grow back” and this can also happen after 10, 15 or 20 years, she warned. Along these lines, Angela Lamarca, an oncologist at the Jiménez Díaz Foundation and spokesperson for ESMO, also calls for caution: “I think that when faced with a patient who has had the disease under control for 10 years, we can say that the cancer is chronic or dormant, but I would not speak of remission.” [o cura] because the truth is that, many times, it is reactivated again later.”
“Immunotherapy still has a long way to go”
Angela Lamarca, oncologist at the Jiménez Díaz Foundation
The scientists consulted maintain that immunotherapy – in all its versions, from checkpoint inhibitors to therapeutic vaccines or the revolutionary CAR-T, among others – has been a game-changer in the treatment of cancer and is being introduced, in one way or another, in more and more tumors. Enriqueta Felip, head of the group Thoracic Tumors and Head and Neck Cancer of the Vall d’Hebron Institute of Oncology (VHIO), says that the introduction of these drugs in some types of lung cancer “has increased the survival rate” of patients with a poor prognosis: “The development in lung cancer was later than that of melanoma, but we already see patients who are still alive and without progressing. We see patients who, after five, six and seven years, continue to come to the clinic,” he explains.
Pilar Barretina, head of medical oncology at the Catalan Institute of Oncology (ICO) in Girona, has a similar opinion: “We talk about cures in a low voice, but we are seeing patients with long remissions. It is spectacular to think that, at the beginning of the 2000s, when I was a resident, there were few options with low efficacy to treat this tumour and now we have long-term survivors.” The doctor, who specialises in gynaecological tumours, says that the “important role” of immunotherapy in cervical and endometrial cancer has already been demonstrated, and they are already the first line of treatment in metastatic phases of both tumours. “In ovarian cancer we do not see that, on its own, immunotherapy has a clear role, but the combination with other strategies is being studied,” adds the oncologist.
Pending duties
Although it is revolutionary, immunotherapy has not yet reached all tumours and does not work in every patient. In fact, overall, only 25% or 30% of patients treated with this therapeutic strategy end up responding, and oncologists are now focused on understanding why it fails in some people or has no effect on certain tumours. “Even if we have good results, there is a significant potential for patients where it does not work and we have to see what mechanisms cause this to happen and how we reverse this lack of efficacy,” admits Barretina.
A recent study led by scientists at the Institute for Research in Biomedicine of Barcelona (IRB) has identified five key characteristics that hinder immunotherapy: the mutational load of the tumor, the microenvironment surrounding the malignant cells or the proliferation capacity of the cancer have all had an influence, but the fact that the patient has undergone previous treatments may also play an important role, they concluded.
The experts consulted say that more precision is needed in identifying the patients who will benefit the most and testing different combinations of drugs with immunotherapy to optimize its potential. Barretina also adds the need to delve deeper into the treatment time: “How long should immunotherapy be administered? And if it is stopped, will it be effective when restarted in all cases that had previously responded?” he asks.
Research is still ongoing, but the outlook is optimistic. Lamarca points to the potential of new immunotherapy strategies that are emerging, such as cell therapy or bispecific drugs, to try to reach tumors (pancreatic tumors, for example) that, for now, resist the onslaught of these drugs. “Immunotherapy still has a long way to go,” he agrees.
#Immunotherapy #achieves #unusual #survival #rates #handful #tumors