Cabozantinib is effective with manageable toxicity for metastatic kidney cancer

The results of an Italian study showed that, in a routine clinical setting, cabozantinib was effective and had acceptable toxicity in patients with metastatic renal cell carcinoma (mRCC) that had progressed after prior treatments. The study was published in Clinical Genitourinary Cancer.

The randomized, phase 3 METEOR trial confirmed a survival benefit of cabozantinib in mRCC patients with progressive disease. The aim of this study was to evaluate the safety and activity of cabozantinib in an unselected population.

In Italy, a managed access program (MAP) is available to allow access of drugs that have not yet been approved or that are not commercially available for patients with severe disease if there no therapeutic alternative and if enrollment in a clinical trial is not possible.

The researchers, led by Giuseppe Procopio, MD, Fondazione IRCCS Istituto Nazionale Tumori in Milan, Italy, collected data from 24 Italian cancer centers where a cabozantinib MAP was available.

Eligible patients were 18 years of age or older with advanced or mRCC with clear or non-clear cell histology. In addition, patients had disease with measurable lesions, including brain metastases, and had received at least one prior anticancer therapy for metastatic disease. Participants had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

Cabozantinib was typically started at 60 mg orally daily on 28-day cycles, although some patients with worse clinical conditions were started at 40 mg daily(if tolerated, the dose was escalated to 60 mg). Treatment modifications, including interruptions and dose reductions, were permitted to manage adverse events (AEs).

Progression-free survival (PFS), defined as the interval between the start of treatment and the first documentation of radiologic and clinical progressive disease or death was assessed. Tumor response or progression was assessed according to RECIST. Other efficacy outcomes evaluated were overall survival (OS) and overall response rate (ORR). Tolerability outcomes were also assessed.

Data from 96 patients treated with cabozantinib within the MAP were collected. Most patients (76%) were male, the median age was 65 years, and most had an ECOG performance status of 1, an intermediate risk as per the Heng prognostic score, and 3 or more metastatic sites. Cabozantinib was second-line therapy in 28 patients (29%), third-line therapy in 18 patients (19%), and a further line of therapy in the remaining 50 patients (52%).

Most patients started at the full dose (69%), 30% started at 40 mg, and one patient started at 20 mg. At the time of the analysis, the median PFS was 8.0 months. The median OS was not reached, with a 1-year OS of 65%.

Although no patients reported a complete response, partial response was observed in 35 patients (36%), while stable disease was observed in 33 patients (34%)—the median duration of response was six months. The remaining 28 patients (30%) experienced progressive disease.

The only significant predictor of survival was treatment line of therapy. Patients who initiated cabozantinib therapy after three or more lines had a decreased risk of progression (P=0.0062) and death (P=0.014). At multivariable analysis, three or more lines of therapy were independently associated with a lower risk of progressive disease (P=0.0043) and a longer survival (P=0.0017).

A dose reduction due to AEs was noted in 40 patients (42%); five patients (5%) discontinued treatment because of AEs. The AEs leading to discontinuation included pulmonary embolism, severe gastrointestinal bleeding, diarrhea, and fatigue. The most frequently observed AEs were asthenia (42%), diarrhea (38%), hand-foot syndrome (30%), mucositis (26%), nausea (21%), and hypertension (21%).

Cabozantinib was active irrespective of the administered dose. No significant difference in terms of PFS and OS was observed between patients treated with a dose of 60 mg or 40 mg.

The investigators acknowledge that limitations of the retrospective study included the small number of patients as well as the lack of a central radiologic review.

“Cabozantinib was effective in everyday clinical practice in a large unselected population of mRCC patients who experience disease progression after prior treatment,” the authors concluded.

They added: “Cabozantinib was also safe, and its toxicity profile was feasible and manageable.”

To read more about this study, click here.