Patients with metastatic renal cell carcinoma (mRCC) who, within the first 2 lines of pharmacotherapy, remain on a drug for 3 months or more have longer overall survival (OS) than those who do not, according to a new study.

In addition, the study revealed a trend toward longer OS among patients who receive more total lines of therapy and found no direct evidence of universal cross-resistance among multiple targeted therapies for mRCC.

Using the Stanford Renal Cell Carcinoma Database, a team led by Alice C. Fan, MD, of Stanford University School of Medicine in Stanford, California, analyzed 194 patients with mRCC with known death dates treated from 2003-2017. The study population, which had a median age of 60 years and median OS time of 16.4 months, received a total of 504 independent lines of single agent therapy, with very few patients receiving combination therapies during the study period. Based on the investigators’ definition of clinical benefit (maintenance on a line of drug therapy for at least 3 months), 293 (58%) lines of therapy were beneficial.

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Median OS was 0.28 years among patients who experienced no clinical benefit within the first 2 lines of targeted therapy compared with 1.74 and 1.71 years for patients who experienced clinical benefit from first-and second-line treatment, respectively, Dr Fan and her colleagues reported in Cancers. Median OS increased from 0.43 years with 1 line of treatment compared with 1.08, 1.82, 2.51, 2.75, and 3.65 years with 2, 3, 4, 5, and 6 lines of treatment, respectively.

The investigators observed that the current treatment paradigm in mRCC is evolving from single-agent targeted therapy to combination regimens aimed at maximizing antitumor activity. “Combination therapy ultimately holds promise for potentially increasing long-term survival, but a major challenge now will be selecting appropriate combinations in the right sequence given the array of drugs currently available for use,” the authors wrote.

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Of the 194 patients, 131 had clear-cell RCC and 21 had non-clear-cell RCC. Based on the risk classification scheme developed by the International Metastatic Renal Cell Carcinoma Database Consortium, 21 patients (11%) had a favorable-risk prognosis and 173 (89%) had an intermediate- or poor-risk prognosis. During the study period, the authors noted, sunitinib was most commonly given as a first-line therapy in 46.9% of patients, followed by pazopanib in 25.8%, and sorafenib in 15.5%. The median number of therapies received per patient was 2. The median duration of therapy per patient was 9.92 months.

Overall, 53 patients (27.3%) experienced a clinical benefit from every line of therapy received and 49 patients (25.3%) experienced no clinical benefit from any line of therapy received. Of the 194 patients in the study, 127 patients (65%) experienced a clinical benefit with first-line treatment.

To address concerns about drug resistance in the context of medications having similar mechanisms of action, Dr Fan and her colleagues examined how frequently patients received a clinical benefit from a later drug after not having had a clinical benefit from a previous one. Of the 194 patients, 41 (21.1%) who experienced no clinical benefit from a prior line of therapy had a clinical benefit from a later line of targeted therapy. Five patients (2.6%) experienced their first clinical benefit in as late as the third line following 2 previous therapeutic failures. The authors highlight the need for biomarkers to increase the clinical benefit that patients receive from treatment.


Chen VJ, Hernandez-Meza G, Agrawal P, et al. Time on therapy for at least three months correlates with overall survival in metastatic renal cell carcinoma. Cancers. 2019;11:1000. doi:10.3390/cancers11071000