"Cola Combo" is used for advanced renal cell carcinoma, reducing the risk of disease progression by 61%

Immunotherapy includes dual immunotherapy (for example, nivolumab + ipilimumab), combined kinase inhibitors (for example, pembrolizumab or avelumab + axitinib, or cabotinib + nivoliyu Monoclonal antibody) has shown good efficacy in metastatic renal cell carcinoma.

Various regimens have been recommended as first-line standard treatments.

Previous studies have shown that lenvatinib (an anti-angiogenic drug) and pembrolizumab as a single agent have shown certain efficacy in renal cancer.

Lenvatinib + everolimus compared with everolimus used in the second-line treatment of renal cancer also significantly improved the PFS of patients.

A phase Ib/II study showed that lenvatinib + pembrolizumab also showed good anti-tumor activity.

CLEAR is a multi-center, open-label, randomized controlled, phase III clinical study designed to evaluate lenvatinib + pembrolizumab or lenvatinib + everolimus versus sunitinib for advanced kidney Efficacy and safety of cell carcinoma.

Recently, the results of the study were published in the New England Journal of Medicine.

Methods The enrolled patients were randomly assigned to receive lenvatinib (20mg, twice a day) + pembrolizumab (200mg IV Q3W) or lenvatinib (18mg) + everolimus ( 5mg, twice a day) or sunitinib (50mg, twice a day) treatment.

The primary endpoint was PFS assessed by the Independent Review Committee (IRC).

Secondary endpoints include OS, ORR, and safety.

Results From October 13, 2016 to June 24, 2019, a total of 1,069 patients from 200 regions in 20 countries were included in the study.

There were 355 patients, 257 patients and 357 patients in the pembrolizumab combination group, everolimus combination group, and sunitinib group, respectively.

The baseline characteristics of the three groups of patients were balanced and comparable.

As of August 28, 2020, with a median follow-up of 26.
6 months, the median PFS of the pembrolizumab combination group and sunitinib group assessed by IRC were 23.
9 months and 9.
2 months, respectively (HR=0.
39, P<0.
001), the median PFS of everolimus combination group and sunitinib group were 14.
7 months and 9.
2 months, respectively (HR=0.
65, P<0.
001).

Figure PFS analysis results PFS subgroup analysis results support the two combined treatment options.

Figure PFS subgroup analysis results of the median OS of the three groups did not reach.

Compared with the sunitinib group, the median OS of the pembrolizumab combination group was significantly improved (HR=0.
66, P=0.
005).

Compared with the sunitinib group, the median OS of the everolimus combination group was not significantly different (HR=1.
15, P=0.
30).

Subgroup analysis showed that most subgroups supported the combination therapy of pembrolizumab+lenvatinib, including PD-L1 positive and negative subgroups.

Compared with the sunitinib group (36%), the ORR of the pembrolizumab combination group (71%, OR=4.
35) and the everolimus combination group (53.
5%, OR=2.
15) were significantly improved.

The safety of the combination therapy is consistent with the known safety of each drug.

Conclusion Compared with sunitinib, lenvatinib + pembrolizumab showed significant improvement in PFS, OS and ORR in patients with advanced renal cell carcinoma; lenvatinib + everolimus showed PFS and Significant improvement in ORR.

References: Motzer R, Alekseev B, Rha SY, et al.
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma.
N Engl J Med.
2021 Feb 13.
doi: 10.
1056/NEJMoa2035716.
Epub ahead of print.
PMID: 33616314.