Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Updated efficacy of lenvatinib (LEN) + pembrolizumab (PEMBRO) versus sunitinib (SUN) in patients with advanced renal cell carcinoma (aRCC) in the CLEAR study (#197)

Camillo G. Porta 1 , Masatoshi Eto 2 , Robert J. Motzer 3 , Ugo De Giorgi 4 , Tomas Buchler 5 , Naveen S. Basappa 6 , Maria Jose Mendez Vidal 7 , Sergei Tjulandin 8 , Se Hoon Park 9 , Bohuslav Melichar 10 , Thomas Hutson 11 12 , Carlos Alemany 13 , Bradley McGregor 14 , Cixin Steven He 15 , Rodolfo Perini 16 , Kalgi Mody 15 , Jodi McKenzie 15 , Basant Ebaid 17 , Toni Choueiri 14
  1. Interdisciplinary Department of Medicine, University of Bari ‘A. Moro’, Bari, Italy
  2. Department of Urology, Kyushu University, Fukuoka, Japan
  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  4. Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy
  5. Department of Oncology, Thomayer University Hospital, Prague, Czech Republic
  6. Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
  7. Department of Medical Oncology, Hospital Universitario Reina Sofía, Maimonides Institute for Biomedical Research of Córdoba, Córdoba, Spain
  8. Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin National Medical Research Center for Oncology, Ministry of Health of the Russian Federation, Moscow, Russian Federation
  9. Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of South Korea
  10. Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic
  11. Department of Medical Oncology, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA
  12. Texas A&M HSC College of Medicine, Bryan, TX, USA
  13. Department of Hematology and Oncology, AdventHealth Cancer Institute, Orlando, FL, USA
  14. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
  15. Eisai Inc., Nutley, NJ, USA
  16. Merck & Co., Inc., Rahway, NJ, USA
  17. Eisai Australia Pty Ltd, Melbourne, Australia

Aims

The phase 3 CLEAR study showed statistically significant PFS (primary endpoint) and OS benefits, and improved ORR with LEN+PEMBRO versus SUN in 1L aRCC. We report updated efficacy and describe patients who completed 2 years of PEMBRO and continued on LEN monotherapy.

Methods

Patients with aRCC and no prior systemic therapy were randomized (1:1:1) to LEN 20mg PO QD + PEMBRO 200mg IV Q3W; LEN 18mg + EVE 5mg PO QD; or SUN 50mg PO QD (4 weeks on/2 weeks off). In this descriptive follow-up analysis (data-cutoff: 31-March-2021), we report updated PFS, ORR, and duration of response (DOR) by independent imaging review per RECIST v1.1 for LEN+PEMBRO and SUN, as well as an exploratory analysis of patients who completed 2 years of PEMBRO per protocol and continued LEN.

Results

Median (m) survival follow-up was 33.7 and 33.4 months in the LEN+PEMBRO (N=355) and SUN (N=357) arms, respectively. Updated efficacy results continued to be improved with LEN+PEMBRO versus SUN (Table). Of patients who completed 2 years of PEMBRO (n=101/355), most (n=65) had IMDC intermediate/poor risk disease; fewer (n=36) had favorable risk disease, consistent with the intention-to-treat population. PEMBRO completers had a 36-month OS-rate of 94.5%; 69 (68.3%) of these patients had treatment-related AEs (TRAEs).

Conclusions

With longer follow-up, LEN+PEMBRO continued to show clinically meaningful benefit versus SUN, consistent with prior results of CLEAR. A large proportion of patients treated with LEN+PEMBRO completed 2 years of PEMBRO and continued LEN monotherapy with ongoing clinical benefit. The results further support LEN+PEMBRO as a standard of care in 1L aRCC.

 

 

LEN+PEMBRO

(N=355)

SUN

(N=357)

mPFS, months (95%CI)

23.3(20.8-27.7)

9.2(6.0-11.0)

   HR (95%CI)

0.42(0.34-0.52)

mOS, months (95%CI)a

NE(41.5-NE)

NE(38.4-NE)

   HR (95%CI)a

0.72(0.55-0.93)

ORR, % (95%CI)

71.0(66.3-75.7)

36.1(31.2-41.1)

  Relative risk, % (95%CI)

1.97(1.69-2.29)

CR, %

17.2

4.2

mDOR, months (95%CI)

26.0(22.2-41.4)

14.7(9.4-16.8)

aPreviously reported.
  1. Previously presented at ESMO Congress 2022, FPN (Final Publication Number): 1449MO, Camillo Porta et al. - Reused with permission ClinicalTrials.gov number: NCT02811861 Funding source: This study was sponsored by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.