Michael B Atkins1, Elizabeth R Plimack2, Igor Puzanov3, Mayer N Fishman4, David F McDermott5, Daniel C Cho6, Ulka Vaishampayan7, Saby George8, Jamal C Tarazi9, William Duggan10, Rodolfo Perini11, Mahgull Thakur12, Kathrine C Fernandez13, Toni K Choueiri14. 1. Georgetown-Lombardi Comprehensive Cancer Center, 3800 Reservoir Road, NW, Washington DC, 20057, USA. Electronic address: mba41@georgetown.edu. 2. Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA, 19111, USA. Electronic address: elizabeth.plimack@fccc.edu. 3. 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: Igor.Puzanov@roswellpark.org. 4. Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL, 33612, USA. Electronic address: fishman@usf.edu. 5. Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA. Electronic address: dmcdermo@bidmc.harvard.edu. 6. Perlmutter Cancer Center at NYU Langone Medical Center, 240 E 38th St 19th floor, New York, NY, 10016, USA. Electronic address: daniel.cho@nyumc.org. 7. Karmanos Cancer Institute, Wayne State University, 4100 John R St, Detroit, MI, 48201, USA. Electronic address: vaishamu@med.umich.edu. 8. Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY, 14203, USA. Electronic address: Saby.George@roswellpark.org. 9. Pfizer Global Product Development-Oncology, 10777 Science Center Dr, San Diego, CA, 92121, USA. Electronic address: jamal.tarazi@pfizer.com. 10. Pfizer Global Product Development-Oncology, 280 Shennecossett Rd, Groton, CT, 06340, USA. Electronic address: william.t.duggan@pfizer.com. 11. Merck & Co, Inc, 2000 Galloping Hill Rd, Kenilworth, NJ, 07033, USA. Electronic address: rodolfo.perini@merck.com. 12. Pfizer, Discovery Park, Ramsgate Rd, Sandwich, CT13 9ND, UK. Electronic address: mahgull.thakur@pfizer.com. 13. Pfizer Global Product Development-Oncology, 1 Portland St, Cambridge, MA, 02139, USA. Electronic address: kathrine.fernandez@pfizer.com. 14. Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. Electronic address: Toni_Choueiri@dfci.harvard.edu.
Abstract
BACKGROUND: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). METHODS: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. RESULTS: 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. CONCLUSIONS: In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.
RCT Entities:
BACKGROUND: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). METHODS: 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. RESULTS: 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. CONCLUSIONS: In patients with advanced RCC with ~4 years of follow-up, combination axitinib/pembrolizumab continued to demonstrate clinical benefit, with no new safety signals.