Hyperprogression to immune blockade followed by a response with cabozantinib in metastatic RCC

Volume 11, Issue 22 of @Oncotarget reported that more and more patients receive first-line treatment with immunotherapy combinations and not all patients respond in metastatic renal cell carcinoma.

After IO-IO progression, the authors stated "we do not have a standard of treatment because it is not available for prospective data on this setting."

Therefore the authors present the case of a patient with metastatic renal cell carcinoma who suffered hyperprogression with IO-IO combination in the first line.

The molecular mechanism to explain patients' response, its the probably crosstalk between MET and NOTCH pathway.

Nowadays, there is not clear the subsequent treatment in those patients who progress to IO-IO first line.

More efforts in biomarker development should be made to better selection of patients' treatment along with the disease.

We present the case of a 50-year-old male who came to the emergency room in March 2019 due to the recent appearance of a mass in the lower region of the left thigh."

Dr. Javier Molina-Cerrillo, The Medical Oncology Department, Ramón y Cajal University Hospital in Madrid Spain

Body CT scan revealed the presence of myocardial implants with extension towards the left ventricular lumen measuring up to 50 mm and pericardial implants, micronodules in both lungs, several lesions in the right gluteus, up to 21 mm and a mass in the upper pole of the left kidney of 6.8 5.5 cm.

The radiological assessment confirmed the clinical suspicion of disease progression with an increase in the renal tumor mass of 7.7 5.9 cm, new intraabdominal implants in the right perirenal space of 4 cm, and left of 3 cm, right hypochondrium of 5.5 cm and left iliac fossa of 4 cm.

The patient began this treatment in early June 2019 with close monitoring of adverse events and tumor assessment.

After 2 weeks of treatment, the patient began to experience significant clinical improvement, recovering to a KI of 90% and with an objective tumor reduction of the visible implants in the left dorsolumbar region, right gluteus muscle, and disappearance in the vast intermediate lesion.

"After 2 weeks of treatment, the patient began to experience significant clinical improvement, recovering to a KI of 90% and with an objective tumor reduction of the visible implants in the left dorsolumbar region, right gluteus muscle, and disappearance in the vast intermediate lesion"

Those data show some activity from TKIs in this setting, but in patients not responding to the IO-IO combination, response durations are below 5 months, representing a subgroup of patients with a particularly poor prognosis.

The Molina-Cerrillo Research Team concluded in their Oncotarget Case Report that there may be hyperprogressions with the new combinations in RCC, the NOTCH pathway may be activated in some patients, and MET inhibition may be key to its control.

In this case, it is demonstrated that a TKI such cabozantinib can control hyperprogression phenomena in 2L of m cc RCC. Clinical trials are currently ongoing in this setting trying to elucidate, prospectively, which is the best strategy.

In this sense, biomarker research is essential to identify those tumor profiles that provide information about the best approach in the first-line setting and beyond.