Axitinib/Pembrolizumab Shows Real-World Efficacy in Frontline Advanced RCC

A real-world analysis showed that patients with advanced renal cell carcinoma in the United States who received the combination of axitinib and pembrolizumab derived similar efficacy with the regimen as those who had received it in randomized clinical trials.

Yousef Zakharia, MD

Yousef Zakharia, MD

A real-world analysis showed that patients with advanced renal cell carcinoma (RCC) in the United States who received the combination of axitinib (Inlyta) and pembrolizumab (Keytruda) derived similar efficacy with the regimen as those who had received it in randomized clinical trials, according to data presented during the 2022 ASCO Genitourinary Cancers Symposium.1

At a median follow-up of 9.67 months (interquartile range, 4.37-14.83), results showed that real-world progression-free survival (PFS) at 3 months, 6 months, 9 months, and 12 months, was achieved by 77.22%, 61.19%, 46.96%, and 39.30% of patients who received the combination (n = 355), respectively. Real-world overall survival (OS) at 3 months and 6 months was achieved by 90.75% and 85.70% of patients, respectively; at 9 months and 12 months, these rates were 78.89% and 73.54%, respectively.

Moreover, the best overall response rate (ORR) achieved with the doublet was 47.9%, which included complete response and partial response rates of 4.23% and 46.20%, respectively. Forty-nine percent of patients achieved stable disease with the regimen, 36.9% experienced disease progression, 6.2% had an indeterminate response to treatment, and 24.5% of patients had missing information.

“Real-world demographic and clinical characteristics were generally consistent with those of patients from randomized controlled trials, and axitinib plus pembrolizumab was an effective first-line treatment for patients with advanced RCC in a real-world setting,” lead study author, Yousef Zakharia, MD, clinical associate professor of Internal Medicine-Hematology, Oncology, and Blood & Marrow Transplantation at the Carver College of Medicine, University of Iowa Healthcare, wrote in a poster on the data.

In April 2019, the FDA approved the combination of axitinib and pembrolizumab for use as a first-line treatment in patients with advanced RCC, based on data from the phase 3 KEYNOTE-246 trial (NCT02853331).2,3 After a median of 12.8 months (range, 0.1-22.0), the estimated percentage of those alive at 12 months in the axitinib/pembrolizumab arm was 89.9% (95% CI, 86.4%-92.4%) vs 78.3% (95% CI, 73.8%-82.1%) in those who received sunitinib (Sutent; HR, 0.53; 95% CI, 0.38-0.74; P < .0001). The median PFS in the investigative and control arms was 15.1 months (95% CI, 12.6-17.7) and 11.1 months (95% CI, 8.7-12.5), respectively (HR, 0.69; 95% CI, 0.57-0.84; P < .001).

For the real-world analysis, investigators set out to understand the clinical characteristics of patients with advanced RCC who were administered axitinib plus pembrolizumab to optimize treatment duration and potentially improve outcomes.

To be included in the analysis, patients were required to have RCC with evidence of stage IV disease, or recurrent metastatic RCC with a metastatic diagnosis date on or after January 1, 2011 to March 31, 2021. Patients also needed to be at least 18 years of age at the time of the index first-line therapy prescription, have evidence of pathology that was consistent with RCC, and have at least 2 clinic encounters on different days.

To perform the analysis, investigators leveraged electronic health record–derived data from the nationwide Flatiron Health de-identified database, which comprises information from approximately 280 cancer clinics spanning around 800 clinical sites throughout the United States.

In the analysis, investigators evaluated tumor response, which was reported as best OR to first-line therapy. Patients were excluded from the analysis of real-world PFS and OS if they did not experience a respective clinical event, as of the last confirmed structured or unstructured activity date and were still alive at the time of study cutoff.

Time to treatment failure (TTF) was defined as time from treatment initiation until treatment discontinuation or therapy change. Treatment duration was determined as the time between first and last treatment, regardless of any stoppages. The study also observed reasons for therapy management and subsequent clinical events following toxicity-related therapy management.

Among the 355 patients included in the analysis, the median age was 68.0 years (range, 60-75), 69.58% were male, and 67.89% were White. Most patients had stage IV disease at diagnosis (55.49%) and clear cell histology (77.18%). Additionally, 55.49% of patients underwent nephrectomy. Moreover, 36.62% of patients had an ECOG performance status of 0, 31.55% had a status of 1, 10.99% had a status of 2, 3.38% had a status of 3, and 17.46% had a missing status. International Metastatic RCC Database Consortium risk scores included favorable (7.61%), intermediate (35.49%), poor/intermediate (23.38%), poor (21.41%), and unknown (12.11%).

Patients received axitinib at an initial dose of 3 mg (3.94%), 5 mg (93.80%), 7 mg (0.28%), 10 mg (0.85%), or other (1.13%), with an initial dose schedule of once daily (1.97%), twice daily (96.34%), or other/unknown (1.69%). Additionally, 76.06% of patients received only axitinib plus pembrolizumab. Other patients received the combination and then went on to receive cabozantinib (Cabometyx; 8.73%), ipilimumab (Yervoy) and nivolumab (Opdivo; 1.97%), everolimus (Afinitor) and lenvatinib (Lenvima; 1.13%), or pazopanib (Votrient; 1.13%).

The duration of treatment for patients with at least 180 days of follow-up was 260 days (range, 150-390). At the time of the analysis, 56.06% of patients had discontinued treatment, 20.00% were still on treatment, 23.38% switched treatment, and 0.56% had augmented treatment status.

Additional data from the analysis indicated that the TTF rates at 3 or more months, 6 or more months, 9 or more months, and 12 or more months were 41.41%, 20.00%, 9.30%, and 6.20%, respectively.

The median duration of treatment was 122 days for patients without treatment modifications, and this was found to be nominally shorter than the 176 days noted in those patients who had treatment modifications. The most frequent first-therapy management event was dose hold (44.23%), followed by discontinuation (27.04%) and dose change (11.55%). Notably, treatment-related adverse effects (AEs) were the most common reason for a first-therapy management event. These AEs led to dose holds in 57.5% of patients, dose changes in 15.0%, and discontinuation in 27.5%.

Approximately 50% of patients who had a dose hold or change as a first-therapy management approach due to AEs continued axitinib and pembrolizumab at their current dose, or at a reduced dose following management. Of the patients who discontinued axitinib and pembrolizumab, 13.6% switched to another treatment.


  1. Zakharia Y, Thomaidou D, Li B, et al. Real-world treatment outcomes of first-line axitinib plus pembrolizumab in patients with advanced renal cell carcinoma in the United States. J Clin Oncol. 2022;40(suppl 6):314. doi:10.1200/JCO.2022.40.6_suppl.314
  2. FDA approves Merck’s KEYTRUDA (pembrolizumab) in combination with Inlyta (axitinib) as first-line treatment for patients with advanced renal cell carcinoma (RCC). Merck; April 22, 2019. Accessed February 25, 2022.
  3. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714
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