Your browser doesn't support javascript.
loading
Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer.
Strickler, John H; Satake, Hironaga; George, Thomas J; Yaeger, Rona; Hollebecque, Antoine; Garrido-Laguna, Ignacio; Schuler, Martin; Burns, Timothy F; Coveler, Andrew L; Falchook, Gerald S; Vincent, Mark; Sunakawa, Yu; Dahan, Laetitia; Bajor, David; Rha, Sun-Young; Lemech, Charlotte; Juric, Dejan; Rehn, Marko; Ngarmchamnanrith, Gataree; Jafarinasabian, Pegah; Tran, Qui; Hong, David S.
Afiliação
  • Strickler JH; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Satake H; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • George TJ; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Yaeger R; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Hollebecque A; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Garrido-Laguna I; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Schuler M; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Burns TF; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Coveler AL; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Falchook GS; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Vincent M; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Sunakawa Y; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Dahan L; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Bajor D; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Rha SY; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Lemech C; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Juric D; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Rehn M; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Ngarmchamnanrith G; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Jafarinasabian P; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Tran Q; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
  • Hong DS; From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gust
N Engl J Med ; 388(1): 33-43, 2023 01 05.
Article em En | MEDLINE | ID: mdl-36546651
ABSTRACT

BACKGROUND:

KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p.G12C-mutated pancreatic cancer are unknown.

METHODS:

We conducted a single-group, phase 1-2 trial to assess the safety and efficacy of sotorasib treatment in patients with KRAS p.G12C-mutated pancreatic cancer who had received at least one previous systemic therapy. The primary objective of phase 1 was to assess safety and to identify the recommended dose for phase 2. In phase 2, patients received sotorasib at a dose of 960 mg orally once daily. The primary end point for phase 2 was a centrally confirmed objective response (defined as a complete or partial response). Efficacy end points were assessed in the pooled population from both phases and included objective response, duration of response, time to objective response, disease control (defined as an objective response or stable disease), progression-free survival, and overall survival. Safety was also assessed.

RESULTS:

The pooled population from phases 1 and 2 consisted of 38 patients, all of whom had metastatic disease at enrollment and had previously received chemotherapy. At baseline, patients had received a median of 2 lines (range, 1 to 8) of therapy previously. All 38 patients received sotorasib in the trial. A total of 8 patients had a centrally confirmed objective response (21%; 95% confidence interval [CI], 10 to 37). The median progression-free survival was 4.0 months (95% CI, 2.8 to 5.6), and the median overall survival was 6.9 months (95% CI, 5.0 to 9.1). Treatment-related adverse events of any grade were reported in 16 patients (42%); 6 patients (16%) had grade 3 adverse events. No treatment-related adverse events were fatal or led to treatment discontinuation.

CONCLUSIONS:

Sotorasib showed anticancer activity and had an acceptable safety profile in patients with KRAS p.G12C-mutated advanced pancreatic cancer who had received previous treatment. (Funded by Amgen and others; CodeBreaK 100 ClinicalTrials.gov number, NCT03600883.).
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Inibidores de Checkpoint Imunológico Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Inibidores de Checkpoint Imunológico Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article