Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial.

Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019).

Fifty-two treatment-naïve patients with advanced RCC were treated with oral axitinib 5 mg twice daily and intravenous pembrolizumab 2 mg/kg every 3 weeks. PFS, duration of response (DoR) and OS were summarised using the Kaplan-Meier method.

At a median follow-up of 42.7 months (95% confidence interval [CI]: 41.1-44.1), median OS was not reached; 38 (73.1%) patients were alive. The probability of being alive at 4 years was 66.8% (95% CI: 49.1-79.5). Median PFS in the overall population was 23.5 months (95% CI: 15.4-30.4). ORR was 73.1%; five patients had complete response. Median DoR was 22.1 months (95% CI: 15.1-34.5). Grade III/IV adverse events (AEs) were reported in 38 (73.1%) patients and 20 (38.5%) discontinued treatment because of AEs: 17 (32.7%) discontinued axitinib, 13 (25.0%) discontinued pembrolizumab, and 10 (19.2%) discontinued both drugs. Common AEs included diarrhoea (84.6%), fatigue (80.8%), hypertension (53.8%), cough (48.1%) and dysphonia (48.1%). There were no new AE terms reported and no treatment-related deaths.

In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.

European journal of cancer (Oxford, England : 1990). 2021 Jan 04 [Epub ahead of print]

Michael B Atkins, Elizabeth R Plimack, Igor Puzanov, Mayer N Fishman, David F McDermott, Daniel C Cho, Ulka Vaishampayan, Saby George, Jamal C Tarazi, William Duggan, Rodolfo Perini, Mahgull Thakur, Kathrine C Fernandez, Toni K Choueiri

Georgetown-Lombardi Comprehensive Cancer Center, 3800 Reservoir Road, NW, Washington DC, 20057, USA. Electronic address: ., Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. Electronic address: ., Vanderbilt University Medical Center, 1211 Medical Center Dr, Nashville, TN, 7232, USA; Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY, 14203, USA. Electronic address: ., Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA. Electronic address: ., Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA. Electronic address: ., Perlmutter Cancer Center at NYU Langone Medical Center, 240 E 38th St 19th floor, New York, NY, 10016, USA. Electronic address: ., Karmanos Cancer Institute, Wayne State University, 4100 John R St, Detroit, MI, 48201, USA. Electronic address: ., Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY, 14203, USA. Electronic address: ., Pfizer Global Product Development-Oncology, 10777 Science Center Dr, San Diego, CA, 92121, USA. Electronic address: ., Pfizer Global Product Development-Oncology, 280 Shennecossett Rd, Groton, CT, 06340, USA. Electronic address: ., Merck & Co, Inc, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: ., Pfizer, Discovery Park, Ramsgate Rd, Sandwich, CT13 9ND, UK. Electronic address: ., Pfizer Global Product Development-Oncology, 1 Portland St, Cambridge, MA, 02139, USA. Electronic address: ., Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address: .