Without fear of exaggeration, the finding discussed below promises
to leave a mark on the history of the world's understanding of cancer
.
The theme: how to improve the success of immunotherapies in cases of surgical tumors.
The answer was given by scientists from the University of California in Los Angeles (UCLA), led by the Catalan Antoni Ribas: they proved that much ground is gained if instead of applying immunotherapies after removing a tumor (as has been done), they start
before surgery
.
The novelty, reflected a few days ago in a paper from the prestigious
The New England Journal of Medicine
(NEJM), is based on such simple reasoning that it is difficult to gauge its scope.
To understand it, two basic explanations.
The first is
what are immunotherapies
, or biological therapies, which have so intensely revolutionized (in the last 15 years) the way of treating some cancers.
These therapies are based on generating an increase in the production of lymphocytes (the cells of the immune system).
In other words, reinforcing their own “little soldiers”, a format that completely distinguishes them from classic cancer therapies, such as chemo, which aim to destroy tumor tissue and (unlike biological therapies) tend to weaken the immune skeleton.
The second is a lesser known fact: in addition to malignant or altered cells,
tumors also have lymphocytes
, both inside and around the cancer.
Cancer immunotherapies consist of generating an increase in the production of lymphocytes.
Some will remember - in relation to the Covid vaccines - that some lymphocytes have "memory", the "immunological memory".
Keep this data.
The novelty now is that the team led by Ribas was able to prove the inconvenience of applying immunotherapies (only) after operating, something that was done by protocol, partly for fear that delaying the surgery (in order to administer the patient some immunotherapy) would mean a waste of vital time.
Ribas and his team proved that it is exactly the other way around.
Adjuvant or neadjuvant-adjuvant
Gabriel Rabinovich
is a biochemist and Conicet Senior Researcher, heads the Glycomedicine Laboratory of the Institute of Experimental Biology and Medicine (IBYME) and is one of the most recognized Argentine scientists in immunotherapies research.
Clarín
asked him how transcendent he considered this novelty.
He was eloquent: he started by saying that "the work is fantastic", he went on to explain that "Ribas is clearly a benchmark" and at the end of the talk he reiterated: "It is brilliant work".
In the paper (“
Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma
”), the researchers focus on a biologic drug (the proper term is "monoclonal antibody") called
pembrolizumab
.
The question they ask is whether, in addition to using it as "adjuvant" (post-surgical therapy to prevent the reappearance of tumor cells), they should also apply it in "neoadjuvant" mode, that is, before surgery.
Rabinovich was emphatic: "The work shows that immunotherapies work better when they are started in what is called neoadjuvant, that is, before surgery, as almost all cancer protocols usually indicate."
Why are neoadjuvant immunotherapies useful?
“Although in some cases it was used before operating, the demonstration that efficacy is much greater when immunotherapy is started earlier has never been so convincing.
This is because biological therapies are based on stimulating lymphocytes that are intratumoral and exhausted”, Rabinovich reinforced.
Because “immunotherapy lifts and stimulates these depleted immune cells,
the reasoning was very simple, very clear, and very compelling.
Brilliant at the same time
.
And it is that if you remove the tumor before, you remove it with the lymphocytes and then the immunotherapy does not have much chance of acting ”, he explained.
It is different with the neoadjuvant strategy: “Giving immunotherapy before surgery stimulates an immune response that raises exhausted lymphocytes, and then a memory response is generated.
Even if you remove the tumor later, the memory persists
”.
The success of immunotherapy before operating
The UCLA clinical study was a Phase 2 trial and included 313 patients from 90 sites in the United States who had advanced melanoma (grades III and IV of the most common type of skin cancer).
Of the total, 159 patients received immunotherapy after the melanoma was removed, while 154 received it before and after (which is why the paper speaks of a "neoadjuvant-adjuvant" treatment).
The conclusions are compelling.
According to the paper, "at a median follow-up of 14.7 months, the neoadjuvant-adjuvant group had
significantly higher event-free survival
than the adjuvant-only group."
Specifically, they clarify, "event-free survival at two years was 72% in the neoadjuvant-adjuvant group, and 49% in the adjuvant group."
The
difference is 23 percentage points
.
In addition, the authors conclude something key, which is that having administered more biological medication did not generate significant differences in terms of toxicity (adverse effects).
Thus, the percentage of patients with treatment-related adverse events "was 12% in the neoadjuvant-adjuvant group, and 14% in the adjuvant-only group," they highlight.
For which cancers could this therapy be useful?
Rabinovich stressed that "it is very important work from a clinical point of view, too" and that, "in theory, it could potentially be
extrapolated to other cancers
where immunotherapies work, that is, tumors sensitive to immunotherapeutics."
For example, he outlined (always in a hypothetical tone), "in head and neck tumors, in lung cancer and in a percentage of gastrointestinal tumors, always - it must be insisted - if they are sensitive to immunotherapies."
Hope is installed in a new path of trials against cancer, closed the scientist: “You have to do it.
It is also necessary to test with other types of tumors to see if this new phenomenon occurs”.
MG
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