PI Agility
In what section can the indication be found and what is it?
Section 1.2
LENVIMA, in combination with pembrolizumab, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
What were the major efficacy outcomes and the additional efficacy outcomes in the CLEAR trial?
The major efficacy outcome measures were PFS, as assessed by independent radiologic review (IRC) according to RECIST v1.1, and OS. Additional efficacy outcome measures included confirmed ORR as assessed by IRC.
Verbalize the major and additional efficacy outcome measures.
LENVIMA in combination with Keytruda demonstrated statistically significant improvements in PFS, OS, and ORR compared with sunitinib.
·KEYTRUDA + LENVIMA demonstrated statistically significant improvement in median PFS (mPFS) vs sunitinib, with a mPFS of 23.9 vs 9.2 months, HR 0.39 (95% CI: 0.32–0.49); P<0.0001
·Median OS was not reached. Analysis of OS demonstrated a statistically significant improvement for KEYTRUDA + LENVIMA vs sunitinib, HR 0.66 (95% CI: 0.49–0.88); P=0.0049
KEYTRUDA + LENVIMA also demonstrated a statistically significant improvement in ORR vs sunitinib: 71% (16% CR & 55% PR) vs 36% (4% CR & 32% PR), (95% CI); P<0.0001
What section can I find the discontinuation rate in? What is the discontinuation rate of LENVIMA, pembrolizumab, or both due to ARs?
Section 6 (page 16)
37%; 26% LENVIMA ONLY, 29% pembrolizumab only, and 13% both drugs
What are the 5 most common ARs (all grades) for KETRUDA + LENVIMA in the CLEAR Study?
Fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), and hypertension (56%)
Verbalize the AR Profile for Lenvima + Keytruda in the CLEAR study.
·ARs are an expected part of treatment with KEYTRUDA + LENVIMA. It is important to set expectations upfront with your patients to report potential side effects
In the CLEAR study, 69% of patients treated with KEYTRUDA + LENVIMA received a dose reduction of LENVIMA due to ARs. The most common adverse reactions (≥5%) resulting in dose reduction or interruption of LENVIMA were diarrhea (26%), fatigue (18%), hypertension (17%), proteinuria (13%)
·The median duration of exposure for patients in the CLEAR study was 17 months (range: 0.1 to 39)
The most common Grade 3-4 ARs in patients treated with KEYTRUDA + LENVIMA in the CLEAR study were diarrhea, fatigue, and hypertension. Serious adverse reactions occurred in 51% of patients receiving LENVIMA and pembrolizumab. Serious adverse reactions in ≥2% of patients were hemorrhagic events (5%), diarrhea (4%), hypertension (3%)
Where is the PI guided strategy locacted for monitoring hypertension? How should hypertension be monitored?
Section 5.1 under Warnings and Precautions
Control blood pressure prior to initiating LENVIMA. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at a reduced dose when hypertension is controlled or permanently discontinue LENVIMA based on severity
What is the recommended dosage of KEYTRUDA + LENVIMA for 1L treatment of adult patients with aRCC?
The recommended dosage of LENVIMA is 20mg orally once daily in combination with pembrolizumab 200mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or until unacceptable toxicity or up to 2 years. After completing 2 years of combination therapy, LENVIMA may be administered as a single agent until disease progression or until unacceptable toxicity.
Verbalize the recommended starting dose and the dose modifications for Lenvima in aRCC.
1st dose reduction: 14mg once daily
2nd dose reduction: 10mg once daily
3rd dose reduction: 8mg once daily
(Table 2 Section 2.6)
What section can I find the efficacy table in?
What was the PFS and OS data?
Section 14.2 (page 38)
PFS: Lenvima + Keytruda 23.9months vs Sunitinib 9.2 months
OS: NR in either arm. OS was statistically significant with Lenvima + Keytruda.
What is the ORR for LENVIMA + KEYTRUDA vs Sunitinib in the CLEAR trial?
Complete Response Rate?
Lenvima + Keytruda 71% vs Sunitinib 36%
Complete Response: Lenvima + Keytruda 16% vs Sunitinib 4%
Verbalize how an HCP would manage diarrhea.
For persistent or intolerable Grade 2 or 3 diarrhea, withhold until it improves to Grade 0 or 1 or baseline.
For Grade 4, permanently discontinue
Table 1 Section 2.6
Which endpoints are statistically significant?
ALL THREE!!!!
PFS, OS, and ORR