Aims
In the CLEAR study, lenvatinib + pembrolizumab significantly improved efficacy outcomes versus sunitinib in first-line treatment of aRCC. Herein, we characterize key ARs (grouped preferred terms per the US prescribing information) in patients with aRCC treated with lenvatinib + pembrolizumab; we also discuss AR management strategies.
Methods
Patients were randomized (1:1:1) to lenvatinib 20mg QD PO + pembrolizumab 200mg IV Q3W (n=355); lenvatinib 18mg QD PO + everolimus 5mg QD PO (n=357); or sunitinib 50mg QD PO (4 weeks on/2 weeks off) (n=357). Key ARs in patients treated with lenvatinib + pembrolizumab are characterized.
Results
Median times (weeks) to first onset of key ARs (any grade, incidence >30%) with lenvatinib + pembrolizumab were: decreased appetite (14.6), diarrhea (20.0), fatigue (4.4), hypertension (3.0), hypothyroidism (14.3), musculoskeletal pain (6.4), nausea (14.4), rash (11.4), and stomatitis (6.6).
Key ARs resulting in dose modifications/discontinuations are shown (Table). The time to onset of grade ≥3 ARs and AR management strategies will be reported.
Conclusions
ARs due to lenvatinib + pembrolizumab were generally consistent with known safety profiles. As will be presented, clinicians play a critical role in prompt identification and AR-directed management; such management may potentially reduce treatment interruption(s) and/or lenvatinib dose reduction.
Table. Lenvatinib + Pembrolizumab (n=352)a
AR,b % |
Lenvatinib Interruption |
Lenvatinib Reduction |
Pembrolizumab |
Lenvatinib |
Pembrolizumab |
Decreased appetite |
4.5 |
7.7 |
2.6 |
0.3 |
0.3 |
Diarrhea |
17.6 |
16.2 |
10.2 |
1.4 |
1.1 |
Fatigue |
11.1 |
9.7 |
7.4 |
0.6 |
0.3 |
Hypertension |
9.1 |
11.9 |
3.1 |
0.9 |
0.3 |
Hypothyroidism |
1.7 |
1.1 |
1.4 |
0.3 |
0.6 |
Musculoskeletal pain |
6.0 |
2.6 |
3.4 |
0.3 |
0.6 |
Nausea |
4.3 |
5.1 |
1.4 |
0.3 |
0.3 |
Rash |
5.7 |
4.0 |
2.8 |
1.4 |
2.3 |
Stomatitis |
5.1 |
4.5 |
1.1 |
0.3 |
0 |
aAll safety analyses included patients who received at least 1 dose of any study drug.
bKey ARs include those with >30% incidence (all grades).