phase 2 study of neoadjuvant cabozantinib in patients with locally advanced non metastatic CORD-Papers-2022-06-02 (Version 1)

Title: Phase 2 study of neoadjuvant cabozantinib in patients with locally advanced non-metastatic clear cell renal cell carcinoma
Abstract: Background: Cabozantinib is a small molecule inhibitor of the tyrosine kinases c-Met AXL and VEGFR2 that has been shown to reduce tumor growth metastasis and angiogenesis. After the promising results from the METEOR CABOSUN and Checkmate-9ER trials cabozantinib was approved for use in patients with advanced renal cell carcinoma (RCC). The increased response rates with cabozantinib in metastatic RCC along with the other neoadjuvant TKI data support an expanded role for cabozantinib in the neoadjuvant setting. Methods: Patients with clinical stage T3Nx or TanyN+ or deemed unresectable by the surgeon with biopsy-proven clear cell RCC were eligible for this study and received cabozantinib at a starting dose of 60 mg daily for 12 weeks. The primary outcome was objective response rate per RECIST v1.1 (complete and partial responses) at week 12 after the administration of cabozantinib as determined by independent radiologist review. Secondary outcomes included safety tolerability clinical outcome (DFS OS) surgical outcome and quality of life. Results: As of 20 September 2021 16 biopsy-proven clear cell RCC patients were treated with neoadjuvant cabozantinib. The median age was 56 years (range: 41-84 years) and 81.2% male. All patients completed 12 weeks of treatment and 15 of them underwent surgery as planned without any delay after completion of 4 weeks wash-out. One patient refused to undergo surgery due to personal reasons and received further systemic treatment. Five patients (31.2%) experienced a partial response and 11 patients had stable disease. There was no progression of disease while on cabozantinib. Median reduction of primary renal tumor size was 24% (range: 6-45%). The one patient who was deemed to be unresectable became resectable at the end of treatment. Two patients were converted from radical to partial nephrectomy. The most common AEs were diarrhea nausea fatigue hypertension anorexia and palmar-plantar erythrodysesthesia syndrome. Intraoperatively we did not experience any immediate complications. Postoperatively no surgical complications related to the drug were noted. No treatment related grade 4 or 5 AEs related to cabozantinib or surgery occurred. Two patients had died at the time of analysis (1 due to COVID and 1 unknown cause). Conclusions: Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced non-metastatic clear cell RCC. Additional data will be reported including long term outcomes correlative studies quality of life and frailty/sarcopenia indices.
Published: 2022
Journal: Journal of Clinical Oncology
DOI: 10.1200/jco.2022.40.6_suppl.340
DOI_URL: http://doi.org/10.1200/jco.2022.40.6_suppl.340
Author Name: Bilen M A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/bilen_m_a
Author Name: Liu Y
Author link: https://covid19-data.nist.gov/pid/rest/local/author/liu_y
Author Name: Nazha B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/nazha_b
Author Name: Brown J T
Author link: https://covid19-data.nist.gov/pid/rest/local/author/brown_j_t
Author Name: Osunkoya A O
Author link: https://covid19-data.nist.gov/pid/rest/local/author/osunkoya_a_o
Author Name: Williams S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/williams_s
Author Name: Session W
Author link: https://covid19-data.nist.gov/pid/rest/local/author/session_w
Author Name: Yantorni L B
Author link: https://covid19-data.nist.gov/pid/rest/local/author/yantorni_l_b
Author Name: Russler G
Author link: https://covid19-data.nist.gov/pid/rest/local/author/russler_g
Author Name: Caulfield S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/caulfield_s
Author Name: Joshi S S
Author link: https://covid19-data.nist.gov/pid/rest/local/author/joshi_s_s
Author Name: Narayan V M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/narayan_v_m
Author Name: Filson C P
Author link: https://covid19-data.nist.gov/pid/rest/local/author/filson_c_p
Author Name: Ogan K
Author link: https://covid19-data.nist.gov/pid/rest/local/author/ogan_k
Author Name: Kucuk O
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kucuk_o
Author Name: Carthon B C
Author link: https://covid19-data.nist.gov/pid/rest/local/author/carthon_b_c
Author Name: Kissick H
Author link: https://covid19-data.nist.gov/pid/rest/local/author/kissick_h
Author Name: Master V A
Author link: https://covid19-data.nist.gov/pid/rest/local/author/master_v_a
license: unk
license_url: [unknown license]
source_x: WHO
source_x_url: https://www.who.int/
who_covidence_id: #covidwho-1779701
url: https://doi.org/10.1200/jco.2022.40.6_suppl.340
has_full_text: FALSE
G_ID: phase_2_study_of_neoadjuvant_cabozantinib_in_patients_with_locally_advanced_non_metastatic