They are two dangerous killers, especially for the male sex. The first – metastatic castration-resistant prostate cancer (mCRPC) – for obvious anatomical reasons, the second (advanced renal cell carcinoma (aRCC) because it is twice as frequent in men and because male patients represent more than two thirds of deaths.
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One molecule for two tumors
For both tumors, the therapies available today have very limited effectiveness: men suffering from castration-resistant prostate cancer often have an unfavorable prognosis, with an estimated survival of 1-2 years, while in patients with advanced kidney cancer or metastatic the survival rate is very low. Now, however, at the American Society of Clinical Oncology Genitourinary Symposium (ASCO GU), underway these days in San Francisco, in the United States, some results have been announced that mark a step forward in the treatment of the two killers. At the center of the therapeutic breakthrough is cabozantinib, a small molecule that inhibits various tyrosine kinase receptors, involved in normal and pathological cellular processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels tumors need to grow), drug resistance, modulation of immune activities and maintenance of the tumor microenvironment. In combination with immunotherapy, cabozantinib improves progression-free survival in both metastatic castration-resistant prostate cancer and advanced renal cell carcinoma.
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Results in prostate cancer
For mCRPC, the detailed primary results of the phase III CONTACT-02 study speak, relating to the association of cabozantinib and atezolizumab compared to treatment with a second new generation hormone therapy (NHT) in patients in whom the disease is measurable in soft tissues extra-pelvic and is in progression after previous NHT therapy. At a median follow-up of 14.3 months, the data demonstrated a statistically significant benefit in progression-free survival of the combination (6.3 months for cabozantinib and atezolizumab compared to 4.2 months obtained with the second new hormone therapy generation). Also regarding overall survival, the data show a trend towards improvement for the combination, but these are still immature data and the study will continue until the next planned analysis, anticipated to 2024.
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Results in kidney cancer
In the case of aRCC, however, the data from the extended four-year follow-up of the phase III CheckMate -9ER study, also presented within the ASCO GU, appear comforting. CheckMate -9ER evaluated the combination of cabozantinib and nivolumab versus sunitinib in patients with this previously untreated carcinoma. With a median follow-up of 55.6 months for overall survival, the combination of the two molecules demonstrated a clinically significant and sustained benefit compared to therapy with sunitinib alone, with a median absolute benefit of 10.5 months (46.5 months versus 36 months). The combination also benefits from progression-free survival, which remained almost double that obtained with sunitinib (16.4 months compared to 8.4). The data from both studies therefore confirm the role of cabozantinib for patients with difficult tumors, an oncology area still full of unmet patient needs, and where positive news is unfortunately a rarity.