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KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

Publication ,  Conference
Uronis, HE; Rushing, C; Blobe, GC; Hsu, SD; Mettu, NB; Wells, JL; Niedzwiecki, D; Hartman, L; Moyer, A; Hurwitz, HI; Strickler, JH
Published in: Journal of Clinical Oncology
January 20, 2021

228 Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m every three weeks and oral C 850mg/m twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After > 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2021

Volume

39

Issue

3_suppl

Start / End Page

228 / 228

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Uronis, H. E., Rushing, C., Blobe, G. C., Hsu, S. D., Mettu, N. B., Wells, J. L., … Strickler, J. H. (2021). KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma. In Journal of Clinical Oncology (Vol. 39, pp. 228–228). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.3_suppl.228
Uronis, Hope Elizabeth, Christel Rushing, Gerard C. Blobe, Shiaowen David Hsu, Niharika B. Mettu, James Leroy Wells, Donna Niedzwiecki, et al. “KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.” In Journal of Clinical Oncology, 39:228–228. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.3_suppl.228.
Uronis HE, Rushing C, Blobe GC, Hsu SD, Mettu NB, Wells JL, et al. KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 228–228.
Uronis, Hope Elizabeth, et al. “KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 228–228. Crossref, doi:10.1200/jco.2021.39.3_suppl.228.
Uronis HE, Rushing C, Blobe GC, Hsu SD, Mettu NB, Wells JL, Niedzwiecki D, Hartman L, Moyer A, Hurwitz HI, Strickler JH. KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 228–228.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2021

Volume

39

Issue

3_suppl

Start / End Page

228 / 228

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences