Broader immune response
Oncologist and researcher Christian Blank from the Netherlands Cancer Institute focuses on a new approach: immunotherapy prior to surgery instead of after, as is currently the case (see illustration). Such a neoadjuvant treatment could potentially have many advantages. "You can determine whether a patient responds to a certain drug, because you can see in the tumor material that is obtained during surgery whether the cancer cells have died", says Blank. "Also, the immune response induced by the immunotherapy is expected to be broader and therefore better. If the tumor is still present in the body, the immune system can learn to recognize the entire tumor with all its variations. The tumor may also be smaller and easier to remove after immunotherapy."
Three treatment schedules
The Netherlands Cancer Institute investigates this treatment strategy in patient with different types of cancers: skin, intestine, breast, stomach, bladder, lung, renal cell, and head and neck cancer. Most advanced are the studies with melanoma patients. A first study that was concluded last year showed positive results but also severe side effects among the participating 20 melanoma patients with lymph node metastases ( phase 1).
That's why the researchers initiated a new study into the safety and efficacy of adjusted dosing schemes of immunotherapy prior to surgery. Together with colleagues in Sydney and Stockholm they compared three different treatment schedules with ipilimumab and nivolumab in 86 melanoma patients with lymph node metastases (this video explains how these checkpoint inhibitors work). Until recently, the standard treatment for patients at this stage of the disease was removal of the lymph nodes. These patients faced a poor prognosis: more than half of them die within 5 years after surgery because they often already have small invisible metastases elsewhere in the body.
Predict
Christian Blank and his colleagues have now published the results of the so-called OpACIN-neo study ( phase 2) in the prestigious journal The Lancet Oncology. The treatment schedule that came out best caused way less severe side effects (20% of the patients) without the efficacy being reduced. Tumor reduction was seen in 23 of these 30 patients (77%), and in 17 of them all cancer cells in the tumor were destroyed (57%). "With this study we confirm that neo-adjuvant therapy is effective in many people, and we have now found a schedule with acceptable side effects", says physician-scientist Lisette Rozeman, first author of the publication. After a follow-up of on average 8 months none of the patients who responded to either one of the three tested treatment schedules had relapsed (0 of 65). In 9 out of the 21 non-responders the disease did recur.
"The elegant aspect of the neoadjuvant approach is that the treatment result seems to be a good predictor for disease recurrence", says Blank. We'll have to wait and see whether this holds true for the long term. "In the future it might even be possible to leave out surgery in patients who respond very well. Our studies also indicate that we might be able predict whether a patient will respond to this drug combination based on a small number of biomarkers. We'll have to investigate this in a larger group though."
