Dr. Robert A. Nagourney, MD
Rare Tumors - Challenges and Triumphs
Updated: Oct 25, 2021
When I am asked how our EVA-PCD laboratory platform might best be applied, I have several responses.
On the one hand, there is my catchphrase, “we cure the curable, treat the treatable and avoid futile care.” What I mean by this is that patients with potentially curable malignancies, e.g., small cell lung cancer, previously untreated ovarian, non-Hodgkin lymphoma, and some leukemias should receive the most effective treatment first line, in order to enhance the likelihood of a cure.
The majority of our patients fall into the second category, those whose tumors can be treated but are less likely to be cured. They include recurrent breast, newly diagnosed lung or pancreas, and colorectal cancer among others.
Finally, in those patients for whom very few options exist, it is arguable that they are best served, when found drug resistant, by avoiding the toxicity of ineffective therapy, or what is known as futile care.
The other way I describe our platform is to explain its capacity to explore treatment options where no reliable guidelines exist. These rare malignancies offer the opportunity to examine a broad array of treatment options, including signal transduction inhibitors in pursuit of heretofore-unrecognized therapeutic directions. Just such a case was submitted to our laboratory this spring
The patient, a 56-year old woman from Brazil, presented in February with a large mass in the left axilla. Biopsy confirmed for an ER, PR and HER2 negative (triple negative) epithelial neoplasm with a proliferative index of 80 percent. The only positive findings were p63 antigen and cytokeratins. Work-up revealed extensive metastatic disease but no other primary could be identified.
The patient underwent surgery followed by aggressive multi-agent chemotherapy. The disease rapidly progressed. Second line therapy proved ineffective. At this point a tissue sample was submitted to our lab. The EVA-PCD analysis revealed an unusual profile with a high degree of activity for sorafenib combinations. Sorefenib was originally developed as BRAF inhibitor and ultimately received FDA approval for the treatment of advanced kidney and liver tumors, associated with the drugs cross reactivity as a VEGF inhibitor. The patient’s study also revealed persistent activity for the beta tublin inhibitors vinorelbine and paclitaxel. The treating physician used our profile to create a novel combination of vinorelbine, paclitaxel combined with sorafenib.
The pretreatment PET CT obtained in June, revealed complete replacement of the liver and extensive soft tissue and nodal metastasis to the lungs, mediastinum, retroperitoneum, as well as innumerable boney metastasis. After failing the previous chemotherapies the patient began this novel drug combination in mid June.
When I arrived in my office this week, I was met with an email that had as an attachment a slide set from a tumor board presentation that described this patient. The introductory slide was, “Tumores Raros.”(Portuguese for Rare Tumors) Included in the presentation was the patient’s history, pathology, immunohistochemistry, treatment overview and serial CT/PET scans. The final slide compared June 2013 PET CT (taken before she began our combination) with an August 2013, (taken after 2 cycles of therapy). The results could not have been more different. The patient had achieved a complete remission. Gone was the extensive hepatic disease. Gone were the boney metastasis. Gone were the dark nodal mets that had scattered across her torso and abdomen like shotgun pellets on an x-ray image. Contrary to every expectation this patient had responded to a drug combination that no one had ever heard of. No one including her treating physician and me.
These experiences remind us that every patient is a unique story, unfolding in real time. This is a stellar example of personalized cancer care, a gleaming testament to the laboratory’s capabilities and even more so to the dedication of the treating physician who broke with all tradition to treat this patient correctly. I am honored to work with this courageous colleague and delighted by this spectacular outcome.