VALENCIA, SPAIN — Targeted therapies have vastly improved survival in renal cell carcinoma (RCC), despite not offering a cure for many patients. More problematically, patients often develop resistance to the drugs.
Add into this complex environment the challenges presented by treating fragile, elderly patients who comprise a significant percentage of those with RCC, and the selection of the best course of treatment becomes trickier still.
Clinical trials provide little insight into the response of fragile patients to targeted therapies. This population is seldom included in trials, so little information is available on how fragile patients tolerate newer therapies, whether dose reduction or dose interruptions help or hinder response, or what adverse events might be most common.
All these questions are of keen interest to clinicians at the VA, who treat a disproportionately older and more fragile population than other healthcare systems.
Spanish researchers at multiple institutions examined the use of cabozantinib, an oral, small-molecule tyrosine kinase inhibitor, in fragile patients. Cabozantinib targets vascular endothelial growth factor receptor (VEGFR), MET, and AXL, all of which play key roles in tumor growth and metastasis.1
The multicenter study enrolled treatment naïve fragile patients aged 70 or older with a diagnosis of metastatic RCC. All participants had ECOG of 0-2 and adequate organ function. Participants received cabozantinib 40 mg once a day until unacceptable toxicity developed or treatment was discontinued for other reasons. Patients who tolerated 40 mg were considered for up-titration to 60 mg, while the dose could be dropped from 40 mg to 20 mg for those who could not tolerate the higher level.
Of the 20 patients in the interim analysis presented at the American Society of Clinical Oncology annual meeting in June, nine remained in treatment. The mean age of the groups was 78 years and 70% were men. Metastatic disease was present at diagnosis in more than two-thirds of the patients. No patients received radiotherapy. One-quarter were vulnerable based on the Vulnerable Elders survey, 45% were frail and at risk of disability using the Short Physical Performance Battery, and 5% had grade 3 comorbidities according to the CIRS-G scale.
The maximum duration of treatment at the time of the report was 20.4 months, with a median duration of 3.3 months. No patients received 60 mg/d and seven patients received the reduced dose of 20 mg/d.
In the 12 evaluable patients, two achieved partial response and seven had stable disease, with a clinical benefit rate of 75%. Common adverse events included asthenia, diarrhea, mucosal inflammation, dysgeusia, and hypothyroidism, which all occurred in 15% to 30% of the patient population. Grade 3 toxicities of thrombocytopenia, pyrexia and hypertension occurred in 5% of patients. Perforated ischemic colitis and skin toxicity led to the withdrawal of two patients from the study.
The researchers noted that “the safety profile is similar to that observed in previous studies. The frequency of toxicities is slightly lower than expected in this aged, fragile population, probably because the patients received treatment at a dose of 40 mg/d, lower than the approved dose.” The findings may be useful to other clinicians treating fragile patients, as it appears cabozantinib provided clinical benefit and was fairly well tolerated at the lower dosage.
- Climent Duran MA, Sanchez-Escribano R, Llabres E, Basterretxea L, Torregrosa MD, Guzman JC, Zambrana F, Fernandez Nunez N, Heras L, Girones R. Pilot study to evaluate safety and efficacy of cabozantinib in aged fragile patients with metastatic renal cell carcinoma. Preliminary results of CABOMAYOR-SOGUG study. J Clin Oncol 40, 2022 (suppl 16; abstr e16524).