Journal article
Outcomes on anti-VEGFR-2/paclitaxel treatment after progression on immune checkpoint inhibition in patients with metastatic gastroesophageal adenocarcinoma
International journal of cancer, Vol.149(2), pp.378-386
03/26/2021
DOI: 10.1002/ijc.33559
PMCID: PMC8488901
PMID: 33739449
Abstract
Through our involvement in KEYNOTE-059, we unexpectedly observed durable responses in two patients with metastatic gastroesophageal adenocarcinoma (mGEA) who received ramucirumab (anti-VEGFR-2)/paclitaxel after immune checkpoint inhibition (ICI). To assess the reproducibility of this observation, we piloted an approach to administer ramucirumab/ paclitaxel after ICI in more patients, and explored changes in the immune microenvironment. Nineteen consecutive patients with mGEA received ICI followed by ramucirumab/paclitaxel. Most (95%) did not respond to ICI, yet after irRECIST-defined progression on ICI, all patients experienced tumor size reduction on ramucirumab/paclitaxel. The objective response rate (ORR) and progression-free survival (PFS) on ramucirumab/paclitaxel after ICI were higher than on the last chemotherapy before ICI in the same group of patients (ORR, 58.8% vs 11.8%; PFS 12.2 vs 3.0 months; respectively). Paired tumor biopsies examined by imaging mass cytometry showed a median 5.5-fold (range 4–121) lower frequency of immunosuppressive forkhead box P3+ regulatory T cells with relatively preserved CD8+ T cells, post-treatment versus pre-treatment (n = 5 pairs). We then compared the outcomes of these 19 patients with a separate group who received ramucirumab/paclitaxel without preceding ICI (n = 68). Median overall survival on ramucirumab/paclitaxel was longer with (vs without) immediately preceding ICI (14.8 vs 7.4 months) including after multivariate analysis, as was PFS. In our small clinical series, outcomes appeared improved on anti-VEGFR-2/paclitaxel treatment when preceded by ICI, in association with alterations in the immune microenvironment. However, further investigation is needed to determine the generalizability of these data. Prospective clinical trials to evaluate sequential treatment with ICI followed by anti-VEGF(R)/taxane are underway.
Details
- Title: Subtitle
- Outcomes on anti-VEGFR-2/paclitaxel treatment after progression on immune checkpoint inhibition in patients with metastatic gastroesophageal adenocarcinoma
- Creators
- Lionel A. Kankeu Fonkoua - Mayo Clinic in FloridaSakti Chakrabarti - Medical College of WisconsinMohamad B. Sonbol - Mayo ClinicPashtoon M. Kasi - University of IowaJason S. Starr - Mayo Clinic in FloridaAlex J. Liu - Department of Oncology Mayo Clinic Phoenix Arizona USAWendy K. Nevala - Mayo ClinicRachel L. Maus - Mayo ClinicMelanie C. Bois - Mayo ClinicHenry C. Pitot - Mayo Clinic in FloridaChandrikha Chandrasekharan - University of IowaHelen J. Ross - Department of Oncology Mayo Clinic Phoenix Arizona USATsung-Teh Wu - Mayo ClinicRondell P. Graham - Mayo ClinicJose C. Villasboas - Mayo Clinic in FloridaMatthias Weiss - ThedaCareNathan R. Foster - Mayo Clinic in FloridaSvetomir N. Markovic - Mayo ClinicHaidong Dong - Department of Urology Mayo Clinic Rochester Minnesota USAHarry H. Yoon - Mayo Clinic in Florida
- Resource Type
- Journal article
- Publication Details
- International journal of cancer, Vol.149(2), pp.378-386
- DOI
- 10.1002/ijc.33559
- PMID
- 33739449
- PMCID
- PMC8488901
- NLM abbreviation
- Int J Cancer
- ISSN
- 0020-7136
- eISSN
- 1097-0215
- Grant note
- DOI: 10.13039/100006108, name: National Center for Advancing Translational Sciences, award: UL1 TR002377
- Language
- English
- Date published
- 03/26/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360153002771
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