A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitors Article Swipe
Farshid Dayyani
,
Joseph Chao
,
Fa-Chyi Lee
,
Thomas H. Taylor
,
Kristen Neumann
,
May T. Cho
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/oncolo/oyae117
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/oncolo/oyae117
Background Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozantinib and pembrolizumab in ICI refractory or resistant mGEA. Methods Investigator-initiated, single-arm, single institution, and phase II study in patients with mGEA. Patients had progressed on ICI and/or had PD-L1 CPS score ≤10%. Cabozantinib dose was 40 mg p.o. daily on days 1-21 of a 21-day cycle, with pembrolizumab 200 mg i.v. on day 1. The primary endpoint was progression-free survival at 6 months (PFS-6). Results Twenty-seven patients were enrolled. Median age 58 years (24-87), female (n = 14), ECOG 0/1 = 13/14, GC/GEJ = 16/11, and non-Hispanic White/Hispanic/Asian = 12/8/7. The primary endpoint was met. After a median follow-up of 31.4 months (range 3.3-42.5), PFS-6 was 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3 months (95% CI 1.7-4.1) and 5.5 months (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). The most common grade (G) treatment-related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension, and muscle cramps (14.8% each). G3-4 TRAE were seen in n = 3 patients (hypertension, thromboembolic event, esophageal perforation; each n = 1). No G5 was observed. Conclusions The addition of cabozantinib to pembrolizumab shows clinical benefit in ICI-resistant or refractory mGEA with a tolerable safety profile. (ClinicalTrials.gov Identifier: NCT04164979. IRB Approved: UCI 18-124, University of California Irvine IRB#20195426.)
Related Topics
Concepts
Pembrolizumab
Cabozantinib
Refractory (planetary science)
Immune checkpoint
Gastroesophageal Junction
Medicine
Cancer research
Oncology
Internal medicine
Immunotherapy
Adenocarcinoma
Cancer
Biology
Astrobiology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/oncolo/oyae117
- https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyae117/58039043/oyae117.pdf
- OA Status
- gold
- Cited By
- 4
- References
- 26
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4399271719
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4399271719Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/oncolo/oyae117Digital Object Identifier
- Title
-
A phase II study of cabozantinib and pembrolizumab in advanced gastric/gastroesophageal adenocarcinomas resistant or refractory to immune checkpoint inhibitorsWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-06-01Full publication date if available
- Authors
-
Farshid Dayyani, Joseph Chao, Fa-Chyi Lee, Thomas H. Taylor, Kristen Neumann, May T. ChoList of authors in order
- Landing page
-
https://doi.org/10.1093/oncolo/oyae117Publisher landing page
- PDF URL
-
https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyae117/58039043/oyae117.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyae117/58039043/oyae117.pdfDirect OA link when available
- Concepts
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Pembrolizumab, Cabozantinib, Refractory (planetary science), Immune checkpoint, Gastroesophageal Junction, Medicine, Cancer research, Oncology, Internal medicine, Immunotherapy, Adenocarcinoma, Cancer, Biology, AstrobiologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
4Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 1Per-year citation counts (last 5 years)
- References (count)
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26Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.tolerable | 243 |
| abstract_inverted_index.3.3-42.5), | 150 |
| abstract_inverted_index.9.0-39.0). | 156 |
| abstract_inverted_index.Background | 1 |
| abstract_inverted_index.California | 255 |
| abstract_inverted_index.University | 253 |
| abstract_inverted_index.approaches | 16 |
| abstract_inverted_index.checkpoint | 12 |
| abstract_inverted_index.esophageal | 216 |
| abstract_inverted_index.inhibitors | 13 |
| abstract_inverted_index.metastatic | 5 |
| abstract_inverted_index.progressed | 70 |
| abstract_inverted_index.refractory | 51, 239 |
| abstract_inverted_index.resistance | 19 |
| abstract_inverted_index.(3.1-14.0), | 171 |
| abstract_inverted_index.Conclusions | 226 |
| abstract_inverted_index.Identifier: | 247 |
| abstract_inverted_index.combination | 44 |
| abstract_inverted_index.single-arm, | 57 |
| abstract_inverted_index.Cabozantinib | 26, 79 |
| abstract_inverted_index.NCT04164979. | 248 |
| abstract_inverted_index.Twenty-seven | 112 |
| abstract_inverted_index.cabozantinib | 46, 230 |
| abstract_inverted_index.institution, | 59 |
| abstract_inverted_index.non-Hispanic | 133 |
| abstract_inverted_index.perforation; | 217 |
| abstract_inverted_index.ICI-resistant | 237 |
| abstract_inverted_index.hypertension, | 198 |
| abstract_inverted_index.pembrolizumab | 48, 94, 232 |
| abstract_inverted_index.respectively. | 172 |
| abstract_inverted_index.(hypertension, | 213 |
| abstract_inverted_index.IRB#20195426.) | 257 |
| abstract_inverted_index.adenocarcinoma | 7 |
| abstract_inverted_index.multi-tyrosine | 29 |
| abstract_inverted_index.thromboembolic | 214 |
| abstract_inverted_index.gastroesophageal | 6 |
| abstract_inverted_index.immunomodulatory | 36 |
| abstract_inverted_index.progression-free | 105 |
| abstract_inverted_index.treatment-related | 189 |
| abstract_inverted_index.CDH1/PIK3CA/CTNNB1 | 181 |
| abstract_inverted_index.(ClinicalTrials.gov | 246 |
| abstract_inverted_index.White/Hispanic/Asian | 134 |
| abstract_inverted_index.Investigator-initiated, | 56 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 90 |
| corresponding_author_ids | https://openalex.org/A5022820783 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 6 |
| corresponding_institution_ids | https://openalex.org/I204250578 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.49000000953674316 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.88444281 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |