Immunotherapy achieves remarkable survival rates in a handful of tumors

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 made a breakthrough 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 immunotherapy’s therapeutic revolution of oncology. Following these positive results, immunotherapy was used to treat other tumors, and it 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 perfected — has achieved remarkable survival rates in a handful of tumors. A study presented this past weekend in Barcelona during the European Society for Medical Oncology (ESMO) Congress and published simultaneously in the New England Journal of Medicine, reveals that almost half of patients with metastatic melanoma treated with immunotherapy are cancer-free 10 years later.

Experts say that the data highlight the potential of immunotherapy in cancer, but admit that there are still pending tasks, such as refining which patients will benefit most from it and exploring how it can be combined with other medications to optimize 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 — 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 over six years, and people who are free from cancer progression at three years have a high likelihood of remaining alive and disease-free at the 10-year time point,” Jedd Wolchock, author of the study and oncologist at the New York-Presbyterian/Weill Cornell Medical Center, said 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 immunotherapy. 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 half of patients treated with this combination therapy will live 10 years or longer without the concern of dying from metastatic melanoma,” said Wolchock.

Other studies presented at the ESMO Congress also showed how immunotherapy 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 tumors 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 participants who received the 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 the study 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 he argued: “These are very important data because we are curing more and more patients.”

Caution needed

This research is a boost for immunotherapy in cancer. And although many oncologists are reluctant to say the word “cure,” the researchers of the melanoma study do argue that it has the potential to cure patients. “These results demonstrate the sustained benefit and impact of dual checkpoint inhibitor therapy on the long-term prognosis of patients with advanced melanoma, highlighting the potential for cure in patients who respond to this type of treatment,” lead study author James Larkin said at the Congress.

However, doctors continue to call for caution and, on Sunday, during the ESMO press conference on these advances, Jessica Hassel, an oncologist at the University Hospital of Heidelberg in Germany, asked for the word “cure” to be used with care, especially if the cancer has spread to other parts of the body. “We prefer the word long-term control because there may be latent cells that grow back,” she warned, explaining this can happen up to 20 years later.

Angela Lamarca, an oncologist at the Jiménez Díaz Foundation and spokesperson for ESMO, also called 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 [or cure] because the truth is that, often it reactivates again later.”

The scientists who spoke to EL PAÍS maintain that immunotherapy — which checkpoint inhibitors, therapeutic vaccines and the revolutionary CAR-T cell therapy — has been a game-changer, and is being used to fight more and more tumors. Enriqueta Felip, head of the Thoracic Tumors and Head and Neck Cancer group at the Vall d’Hebron Institute of Oncology (VHIO) in Spain, says that the use of these drugs “has increased the survival rate” of some lung cancer patients with a poor prognosis: “We are seeing patients who, after five, six and seven years, continue to come to the clinic,” she said.

Pilar Barretina, head of medical oncology at the Catalan Institute of Oncology (ICO) in Girona, has a similar opinion: “We are whispering about cures, but we are seeing patients with long remissions.” The doctor — who specializes in gynecological tumors — says that immunotherapy plays an “important role” in cervical and endometrial cancer, and is the first line of treatment in metastatic phases of both tumors.

More work to be done

Although it is revolutionary, immunotherapy is still not used on every tumor, not does it work in every patient. In fact, overall, only 25% or 30% of patients respond to immunotherapy. Oncologists are trying to understand why it fails in some people or has no effect on certain tumors. “We have to see what mechanisms cause this to happen and how we reverse this lack of efficacy,” admitted Barretina.

A recent study led by scientists at the Institute for Research in Biomedicine of Barcelona (IRB) identified five key characteristics that hinder immunotherapy, including the tumor’s mutational load; the microenvironment surrounding the malignant cells and the cancer’s proliferation capacity. But the study also found that whether a patient had undergone previous treatment was also a factor.

Experts tell EL PAÍS that there needs to be more precision when it comes to identifying the patients who will benefit the most from immunotherapy, and argue that different combinations of drugs should be tested with immunotherapy to optimize its potential. Barretina also adds that there also needs to be more research into 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 asked.

Research is still ongoing, but the outlook is optimistic. Lamarca highlights the potential of the new immunotherapy strategies under development — such as cell therapy or bispecific drugs — which are seeking to target tumors (pancreatic tumors, for example) that have been resistant until now. “Immunotherapy still has a long way to go,” he agrees.

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