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Cabozantinib extends PFS as first-line therapy for metastatic renal cell carcinoma

MADRID — Cabozantinib significantly extended PFS compared with sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma, according to updated results from the CABOSUN trial presented at the European Society for Medical Oncology Congress.

The results, based on independent review committee analysis, confirmed previously reported investigator-assessed PFS results.

“The CABOSUN results support the potential of cabozantinib to become a new therapeutic option for previously untreated patients following their diagnosis with advanced kidney cancer,” Toni K. Choueiri, MD, director of Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, told HemOnc Today. “These updated analyses from CABSOSUN consistently show that cabozantinib provided a statistically significant decrease in the rate of disease progression or death compared with sunitinib, a current standard of care, which suggests it could change the way we treat first-line renal cell carcinoma.”

Cabozantinib (Cabometyx, Exelixis) — a small molecule inhibitor of the MET, AXL and VEGFR2 tyrosine kinases — received FDA approval last year for treatment of patients with advanced renal cell carcinoma who received prior antiangiogenic therapy.

The CABOSUN trial assessed cabozantinib vs. sunitinib (Sutent, Pfizer) as initial targeted therapy for patients with poor- or intermediate-risk clear-cell metastatic renal cell carcinoma.

“The CABOSUN trial included patients with intermediate or poor prognostic factors per the IMDC criteria; in addition, patients had a notable number of other independent adverse prognostic risk factors,” Choueiri said. “These included a high rate of bone metastases, two or more sites of metastatic disease, ECOG 2 performance status, and lack of prior nephrectomy. This patient population fares poorly and is in need of new therapies to better control their disease.”

Researchers randomly assigned 79 patients to 60 mg cabozantinib daily. The other 78 patients received 50 mg sunitinib daily, administered on a 4-weeks-on, 2-weeks-off schedule.

Investigator-assessed PFS analysis presented at last year’s ESMO Congress showed cabozantinib was more effective than sunitinib (median, 8.2 months vs. 5.6 months; HR = 0.66; 95% CI, 0.46-0.95).

At ESMO this year, Choueiri presented PFS analyses per blinded independent radiology committee, as well as an update of OS based on a data cutoff of July 1.

The independent committee assessed radiographic images of 156 of 157 enrolled patients. Results showed cabozantinib significantly prolonged median PFS compared with sunitinib (8.6 months vs. 5.3 months; HR = 0.48; 95% CI, 0.31-0.74).

Results showed consistent benefit across subgroups based on IMDC risk group and presence of bone metastases.

“Any improvement in PFS for this patient population is a positive step in advancing care for this difficult-to-treat disease,” Choueiri told HemOnc Today. “And we have to remember that the 3.3-month improvement in PFS is the median and does not reflect longer duration felt by some patients.

“Furthermore, the low rate of response and limited duration of PFS on sunitinib highlights the unmet medical need for this patient population,” he added. “The PFS results are very strong and consistent between the independent review committee and investigator studies, indicating greater disease control on cabozantinib, which signifies a potential new treatment for patients who currently have limited options.”

After median follow-up of 30.8 months, results showed cabozantinib-treated patients also achieved longer median OS (26.6 months vs. 21.2 months; HR = 0.79; 95% CI, 0.53-1.2), although the difference did not reach statistical significance.

Safety profiles of the drugs appeared consistent with prior reports. A comparable percentage of cabozantinib- and sunitinib-treated patients experienced grade 3 or grade 4 adverse events (68% vs. 65%). Sixteen patients in each group discontinued treatment due to adverse events. – by Mark Leiser

Reference:

Choueiri T, et al. Abstract LBA38. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.

MADRID — Cabozantinib significantly extended PFS compared with sunitinib as initial targeted therapy for patients with metastatic renal cell carcinoma, according to updated results from the CABOSUN trial presented at the European Society for Medical Oncology Congress.

The results, based on independent review committee analysis, confirmed previously reported investigator-assessed PFS results.

“The CABOSUN results support the potential of cabozantinib to become a new therapeutic option for previously untreated patients following their diagnosis with advanced kidney cancer,” Toni K. Choueiri, MD, director of Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, told HemOnc Today. “These updated analyses from CABSOSUN consistently show that cabozantinib provided a statistically significant decrease in the rate of disease progression or death compared with sunitinib, a current standard of care, which suggests it could change the way we treat first-line renal cell carcinoma.”

Cabozantinib (Cabometyx, Exelixis) — a small molecule inhibitor of the MET, AXL and VEGFR2 tyrosine kinases — received FDA approval last year for treatment of patients with advanced renal cell carcinoma who received prior antiangiogenic therapy.

The CABOSUN trial assessed cabozantinib vs. sunitinib (Sutent, Pfizer) as initial targeted therapy for patients with poor- or intermediate-risk clear-cell metastatic renal cell carcinoma.

“The CABOSUN trial included patients with intermediate or poor prognostic factors per the IMDC criteria; in addition, patients had a notable number of other independent adverse prognostic risk factors,” Choueiri said. “These included a high rate of bone metastases, two or more sites of metastatic disease, ECOG 2 performance status, and lack of prior nephrectomy. This patient population fares poorly and is in need of new therapies to better control their disease.”

Researchers randomly assigned 79 patients to 60 mg cabozantinib daily. The other 78 patients received 50 mg sunitinib daily, administered on a 4-weeks-on, 2-weeks-off schedule.

Investigator-assessed PFS analysis presented at last year’s ESMO Congress showed cabozantinib was more effective than sunitinib (median, 8.2 months vs. 5.6 months; HR = 0.66; 95% CI, 0.46-0.95).

At ESMO this year, Choueiri presented PFS analyses per blinded independent radiology committee, as well as an update of OS based on a data cutoff of July 1.

The independent committee assessed radiographic images of 156 of 157 enrolled patients. Results showed cabozantinib significantly prolonged median PFS compared with sunitinib (8.6 months vs. 5.3 months; HR = 0.48; 95% CI, 0.31-0.74).

Results showed consistent benefit across subgroups based on IMDC risk group and presence of bone metastases.

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“Any improvement in PFS for this patient population is a positive step in advancing care for this difficult-to-treat disease,” Choueiri told HemOnc Today. “And we have to remember that the 3.3-month improvement in PFS is the median and does not reflect longer duration felt by some patients.

“Furthermore, the low rate of response and limited duration of PFS on sunitinib highlights the unmet medical need for this patient population,” he added. “The PFS results are very strong and consistent between the independent review committee and investigator studies, indicating greater disease control on cabozantinib, which signifies a potential new treatment for patients who currently have limited options.”

After median follow-up of 30.8 months, results showed cabozantinib-treated patients also achieved longer median OS (26.6 months vs. 21.2 months; HR = 0.79; 95% CI, 0.53-1.2), although the difference did not reach statistical significance.

Safety profiles of the drugs appeared consistent with prior reports. A comparable percentage of cabozantinib- and sunitinib-treated patients experienced grade 3 or grade 4 adverse events (68% vs. 65%). Sixteen patients in each group discontinued treatment due to adverse events. – by Mark Leiser

Reference:

Choueiri T, et al. Abstract LBA38. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.

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