The Future of Cancer Therapy (March 25, 2021)

The recent emergence of immunotherapy has changed the landscape of cancer treatment in a significant way. Diseases that were refractory to standard treatment like advanced melanoma, have succumbed to effective therapy. Now, for the first time, we dare to speak of a cure in advanced lung cancer, which is the most common cancer in the world. Currently, there are three major approaches of systemic treatment of cancer: Immunotherapy, chemotherapy and targeted therapy. While chemotherapy targets both the normal cell and the cancer cell, targeted therapy only attacks the cancer cell and does not damage the normal one. This is why the side effects of the latter are different from those of chemotherapy and less brutal. Contrary to both, immunotherapy does not target the cancer cell directly; it targets the immune system in the patient’s body and enhances this system in a manner that makes it capable of recognizing the cancer cell as a foreign invader and destroying it.

There are ample data in the literature on the combination of immunotherapy plus chemotherapy, and some data on the combination of immunotherapy plus targeted therapy, but there have been no data on the combination of all three major approaches in the treatment of cancer at the same time. For this reason, we at Salem Oncology Center, started to explore the efficacy of this combination five years ago. Our work has shown that not only is this combination extremely effective and produces a very high response rate, it was also associated with minimal adverse effects.

The response rate we have seen with the combination has not been seen before in advanced and refractory cancer. The patients we initially treated were all considered terminal and did not have a known established standard treatment. Most of them were considered ineligible for additional treatment by most cancer centers. In this category of patients, the maximum overall response rate (complete plus partial response) reported in the literature, is less than 15%. With our combination, we have achieved an overall response rate of 94%. In my opinion, this is remarkable. Our manuscript was published in a peer reviewed journal, Trends in Cancer Research, issue December 29, 2020. Before this publication our work was published in abstract form in the Journal of Clinical Oncology in the context of the Annual Meetings of the American Society of Clinical Oncology, June 2019 and June 2020.

Our work has introduced a new approach to the treatment of cancer. This was the first time the combination of immunotherapy plus chemotherapy plus targeted treatment was used in the treatment of advanced and refractory cancer. In addition, this treatment was highly personalized. Patients who have the same type of cancer usually receive the same protocol, but in our program, treatment is tailored to the individual patient. Consequently, every patient receives a treatment different from the other patient. Though every patient receives the combination of immunotherapy plus chemotherapy plus targeted treatment, no two patients receive identical treatment. Chemotherapy was designed on the basis of the histopathological diagnosis and prior treatment, while both immunotherapy and targeted therapy were both designed on the basis of the biologic and genomic profile of the tumor. In every patient, tumor tissue was sent for extensive evaluation for biological markers and targetable mutations.

A distinguished feature of our program, named ICTriplex, is that its efficacy was not confined to a single disease. This treatment was shown to be efficacious in a broad variety of cancer diseases like lung, pancreas, gastrointestinal, lymphomas and liver. Of the patients we treated, not a single one had progression of disease after the first cycle of treatment.

Another finding is that this treatment appears to cross the blood-brain barrier and makes a major impact on metastatic cancer to the brain. Three patients with lung cancer who had extensive disease in the brain achieved a complete response in the brain without the need for radiation therapy. This is another advantage of this approach as many of the drugs in standard treatment protocols, do not cross the blood-brain barrier and do not achieve a significant response in the brain.

Our work has certainly provided a new option for patients considered not to have other options. In fact, three of four patients considered terminal at leading cancer centers achieved a complete response. Therefore, medical oncologists who feel that their patients have no known options, may wish to try the ICTriplex program. Because of the very impressive response rate, wide-spectrum activity and minimal toxicity, I believe this approach represents a model for what treatment of cancer can be in the future. In my 53 years of experience in cancer medicine and research, I have learned humility and therefore, I would recommend that this combination be put to additional testing in future large clinical trials to define its exact role in the treatment of cancer.

*Chair, The Philip A. Salem, M.D. Chair in Cancer Research, Baylor St. Luke’s Medical Center. President, Salem Oncology Centre

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