KEYTRUDA (pembrolizumab) + Axitinib in RCC
KEYTRUDA® (pembrolizumab) with axitinib: approved for first line treatment of advanced renal cell carcinoma (RCC) in adults1
Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland) [External links]
The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes.
KEYTRUDA plus axitinib achieved superiority across OS, PFS and ORR versus sunitinib.2,3
The dual primary end points were overall survival and progression-free survival. The key secondary end point was the objective response rate (complete response +partial response). Other secondary end points included duration of response and safety. Efficacy was assessed in the intention-to-treat population, which included all patients who underwent randomization. Safety was assessed in the as-treated population, which included all randomly assigned patients who received one or more doses of trial treatment.
The number of patients in each IMDC category are as follows:
| IMDC prognostic risk – no. (%) | Pembrolizumab-axitinib | sunitinib |
|---|---|---|
| Favourable | 138 (31.9) | 131 (30.5) |
| Intermediate | 238 (55.1) | 246 (57.3) |
| Poor | 56 (13.0) | 52 (12.1) |
Primary endpoints: overall survival and progression-free survival in the intention-to-treat population2
Secondary end points: Objective response rate, duration of response and safety2
- Overall Survival in the intention-to-treat population: Not Reached (HR=0.53, 95% CI, 038-0.74) p <0.0001)
- Progression Free Survival in the intention-to-treat population: Median progression-free survival was 15.1 months in the pembrolizumab–axitinib group and 11.1 months in the sunitinib group (hazard ratio for disease progression or death, 0.69; 95% CI, 0.57 to 0.84; P<0.001).
Updated Analysis, 42.8 months median follow up
No conclusion can be drawn from the follow-up data as no statistical analysis was performed.
Kaplan-Meier estimates of OS in KEYNOTE-4262
Adapted from Rini et al. 2021.3 OS was assessed in the intention-to-treat population, defined as all patients who underwent randomisation.3
Median overall survival was 45.7 months (43.6–not reached) for KEYTRUDA plus axitinib and 40.1 months (34.3–44.2) for sunitinib. Adapted from Rini BI et al. 2021.2
Latest median follow-up data is presented. Data cut off 11 January 2021. Median follow up 42.8 months (35.6-50.6 months). Adapted from Rini BI et al. 2021.2
In an earlier analysis when patients had a median follow up of 16.6 months (0.1–26.3 months), the hazard ratio (95% CI) for the overall population was 0.59, p=0.0001. P value is nominal only. Adapted from Rini BI et al. 2019.*1
Hazard ratio presented depicts the hazard ratio for death
*Based upon p value threshold (alpha allocation) planned for the first interim analysis of KEYNOTE-426.
aBecause superiority of KEYTRUDA plus axitinib was shown at the first interim analysis, no alpha was allocated to overall survival; only nominal p values are reported.
KEYTRUDA plus axitinib in first-line treatment of aRCC
SUPERIOR PROGRESSION-FREE SURVIVAL (PFS) vs. SUNITINIB2,3
Adapted from Rini et al. 2021.3 PFS was assessed in the intention-to-treat population, defined as all patients who underwent randomisation.3
Latest median follow-up data is presented. Data cut off 11 January 2021. Median follow-up 42.8 months (35.6-50.6 months). Adapted from Rini BI et al. 2021.2
Hazard ration presented depicts the hazard ratio for disease progression and death.
*Based upon p value threshold (alpha allocation) planned for the first interim analysis of KEYNOTE-426.
aBecause superiority of KEYTRUDA plus axitinib was shown at the first interim analysis, no alpha was allocated to overall survival; only nominal p values are reported.
KEYTRUDA axitinib in first-line treatment of aRCC
SUPERIOR OVERALL RESPONSE vs. SUNITINIB2,3
Adapted from Rini BI et al. 2021.2
Latest median follow-up data is presented. Data cut off 11 January 2021. Median follow-up 42.8 months (35.6-50.6 months). Adapted from Rini BI et al. 2021.2
aBecause superiority of KEYTRUDA plus axitinib was shown at the first interim analysis, no alpha was allocated to objective response; only nominal p values are reported.
Adverse events of any cause that occurred in 10% or more of patients in the as-treated population in KEYNOTE-4263
For the most up to date safety information, please refer to the SPC.1
Adapted from Rini BI, et al., 20193
The most common reason for treatment discontinuation was disease progression. 88 patients discontinued due to disease progression in the prembrolizumab plus axitinib arm vs 147 patients in the sunitinib arm.3
Safety was assessed in the as-treated population, which included all randomly assigned patients who received one or more doses of trial treatment.3
Adverse events of any cause occurred in 98.4% of the 429 patients in the pembrolizumab–axitinib group who received the assigned treatment and in 99.5% of the 425 patients in the sunitinib group who received the assigned treatment.3
These events were of Grade 3 or higher in 75.8% of the patients in the pembrolizumab–axitinib group and in 70.6% of the patients in the sunitinib group;2 67.8% of the patients in the pembrolizumab–axitinib group and 63.8% of the patients in the sunitinib group had events of Grade 3 or higher that were attributed by the investigator to trial treatment.2
In the pembrolizumab–axitinib group, adverse events of any cause led to discontinuation of either or both drugs in 30.5% of patients, discontinuation of both drugs in 10.7%, interruption of either drug in 69.9%, and dose reduction of axitinib in 20.3%.3
The median time to discontinuation of both pembrolizumab and axitinib because of adverse events of any cause was 105.5 days, and the median time to discontinuation of pembrolizumab because of adverse events of any cause was 65 days.3
In the sunitinib group, adverse events of any cause led to discontinuation in 13.9% of patients, interruption in 49.9%, and dose reduction in 30.1%.3
Abbreviations
CI = Confidence Interval; CR = Complete Response; DOR = Duration Of Response; HR = Hazard Ratio ; IMDC = International Metastatic RCC Database Consortium; ORR = Objective Response Rate; OS = Overall Survival; PD-L1 = Programmed Death Ligand 1; PFS = Progression-Free Survival; PR = Partial Response; RECIST = Response Evaluation Criteria in Solid Tumors
References
- KEYTRUDA Summary of Product Characteristics.
- Rini BI et al. Presented at ASCO 2021 Virtual Annual Meeting.
- Rini BI, Plimack ER, Stus V, et al; for the KEYNOTE-426 investigators. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116–1127.
Supporting documentation
Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland)
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