Additional Practice-informing Adverse Event Patterns and Management in the KRYSTAL-1 Phase 2 Study of Adagrasib (MRTX849) in Patients With KRASG12C-mutated Non--Small Cell Lung Cancer...Academy of Oncology Nurse & Patient Navigators (AONN+) 14th Annual Navigation & Survivorship Conference, November 15–19, 2023, San Antonio, Texas.
Background: Adagrasib, a KRASG12C inhibitor selected for favorable properties, including a long half-life (23 hr), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration, has demonstrated clinical activity in patients with KRASG12C-mutated non--small cell lung cancer (NSCLC) w...
| Publicado en: | Journal of Oncology Navigation & Survivorship Vol. 14; no. 11; pp. 350 - 351 |
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| Autores principales: | , , , , , , , , , , , |
| Formato: | abstract proceedings research Journal Article |
| Publicado: |
Amplity Health
Nov2023
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=173646436&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 173646436 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 21660999 EUN0 jtl: Journal of Oncology Navigation & Survivorship issn: 21660999 maglogo: N pubinfo: dt: Nov2023 vid: 14 iid: 11 pid: 82137 pub: Amplity Health place: East Windsor, New Jersey artinfo: ui: 173646436 173646436 173646436 173646436 ppf: 350 ppct: 1 formats: fmt: @attributes: type: P tig: atl: Additional Practice-informing Adverse Event Patterns and Management in the KRYSTAL-1 Phase 2 Study of Adagrasib (MRTX849) in Patients With KRASG12C-mutated Non--Small Cell Lung Cancer...Academy of Oncology Nurse & Patient Navigators (AONN+) 14th Annual Navigation & Survivorship Conference, November 15–19, 2023, San Antonio, Texas. aug: au: Zhang, Jun Leventakos, Konstantinos Leal, Ticiana A. Pennell, Nathan A. Barve, Minal Paulson, Scott Bazhenova, Lyudmila Johnson, Melissa L. Chao, Richard C. Velastegui, Karen Qian, Chunlin Spira, Alexander affil: University of Kansas Medical Center, Kansas City, KS sug: subj: Carcinoma, Non-Small-Cell Lung Drug Therapy Antineoplastic Agents Therapeutic Use Antineoplastic Agents Adverse Effects Mutation Drug Effects Treatment Outcomes Evaluation Practice Patterns Evaluation Adverse Drug Event Prevention and Control Congresses and Conferences Texas Texas ab: Background: Adagrasib, a KRASG12C inhibitor selected for favorable properties, including a long half-life (23 hr), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration, has demonstrated clinical activity in patients with KRASG12C-mutated non--small cell lung cancer (NSCLC) with an objective response rate (ORR) of 43% and a median overall survival of 12.6 months, including patients with CNS metastases (intracranial ORR per modified response assessment in neurooncology brain metastases, 33%). Objective: To report additional practice-informing safety analyses from KRYSTAL-1 cohort A, a registrational phase 2 cohort, evaluating adagrasib capsules 600 mg orally twice daily in patients with previously treated NSCLC. Methods: KRYSTAL-1 is a multicohort phase 1/2 study of adagrasib in patients with advanced solid tumors harboring a KRASG12C mutation. Analyses reported here include time to onset (TTO), time to resolution (TTR), and the management of treatment-related adverse events (TRAEs), including gastrointestinal (GI)-related TRAEs. Results: As of October 15, 2021, 116 patients (female, 56%; median age, 64 y; Eastern Cooperative Oncology Group performance status 1, 84%) received adagrasib; median follow-up was 12.9 months (95% CI, 11.8-13.5), and median treatment duration was 5.7 months (range, 0-19.6 mo). Any grade TRAEs occurred in 97% of patients: grade 1-2, 53%; grade ≥3, 45%. Overall, >92% of new-onset TRAEs occurred within the first 3 cycles; few new grade ≥3 TRAEs occurred after cycle 3. TRAEs led to dose reduction, interruption, and discontinuation in 52%, 61%, and 7% of patients, respectively. GI-related TRAEs occurred in 85%, leading to dose reductions in 20%. Median TTO of GI TRAEs was 3 days (interquartile range, 1-12 d) and of increased alanine transaminase/aspartate aminotransferase levels was 22 days (interquartile range, 15-35 d); median TTR of these TRAEs after initial occurrence was 14 days (range, 5-43 d) and 12 days (range, 7-21 d), respectively. GI TRAEs were manageable with antidiarrheals (48%) and antiemetics/antinauseants (87%). Conclusions: Adagrasib demonstrated a manageable adverse event profile in pretreated patients with KRASG12C-mutated NSCLC. Most TRAEs were low grade, occurred early in treatment, and resolved quickly, resulting in a low (7%) discontinuation rate. Funding: This study (NCT03785249) was sponsored by Mirati Therapeutics, Inc. Third-party medical writing support, under the direction of the authors, was provided by Hannah Preston, BSc, of Ashfield MedComms, an Inizio company, and was funded by Mirati Therapeutics, Inc. This abstract was previously presented at the European Society for Medical Oncology (ESMO) Conference 2022; Final Publication Number: 1133P. The study was previously published in Zhang J, et al. Annals Oncol. 2022;33(suppl 7):S1068-S1069. doi: http://doi.org/10.1016/j.annonc. 2022. 07.1257. Data previously published in Zhang J, Johnson M, Barve M, et al. Oncologist. 2023;28(4):287-296. Reused with permission. pubtype: Academic Journal doctype: abstract proceedings research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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