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Cited by 15Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentLung Cancer Research Studies

S1507: Phase II study of docetaxel and trametinib in patients with G12C or non-G12C KRAS mutation positive (+) recurrent non-small cell lung cancer (NSCLC).

Gadgeel, Shirish M., Miao, Jieling, Riess, Jonathan W., Mack, Philip C., Gerstner, Gregory James, Burns, Timothy F., Taj, Asma, Akerley, Wallace L. +4 more·2019·Journal of Clinical Oncology
DOI 10.1200/jco.2019.37.15_suppl.9021
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Abstract

9021 Background: KRAS+ NSCLC remains the most common genetically defined subset of NSCLC. Despite promising pre-clinical data, MEK inhibitors have failed to provide meaningful clinical benefit both as single agents and in combination with chemotherapy in KRAS+ NSCLC patients. Pre-clinical data suggest that efficacy of MEK inhibitors in KRAS+ NSCLC differs based on specific KRAS mutations such as G12C and by status of p53 or LKB1 mutations. We conducted a phase II study to assess the efficacy of docetaxel plus trametinib in KRAS+ NSCLC patients and in specific genetic subsets. Methods: KRAS+ NSCLC patients who had progressive cancer following 1 or 2 prior regimens were eligible. Docetaxel was given at 75 mg/m2 every 3 weeks and trametinib orally at 2 mg daily. The study was 2-stage design to rule out a response rate (RR) of 17% at the 3% level with 90% power if the true rate were 37%. The study required 45 pts with a futility analysis at 30 pts; 13/45 responses would indicate a success. RR was also assessed in G12C and non-G12C cohorts and will be assessed according to presence of co-mutations in p53 and LKB1. Progression free survival (PFS) and overall survival (OS) were secondary endpoints. Multivariate analysis including age, sex, number of prior treatments, prior immunotherapy (IO) and G12C status was conducted. Results: The study enrolled 54 evaluable pts (19 G12C, 9 G12D, 9 G12A); median age 65 years; female 57%; never smokers 7%; adenocarcinoma 89%; liver metastases 31%; 2 prior regimens 70%; prior IO 57%. Outcomes are summarized in Table. Median duration of therapy was 2.2 months and most common toxicities were fatigue (78%), diarrhea (68%), nausea (57%) and vomiting (28%). One patient died of treatment related respiratory failure. There was a trend for worse PFS (HR- 1.86, p = 0.06) and survival (HR- 1.80, p = 0.14) in G12C patients. Analysis of efficacy data according to co-mutations in p53 or LKB1 is ongoing. Conclusions: Docetaxel plus trametinib met the primary endpoint of the study, with a RR of 33% and median survival of 11.1 months in patients with KRAS+ NSCLC, 70% of whom had received 2 prior regimens. Although, there was no statistical difference between KRAS+ subtypes, these data suggest that outcomes may differ between G12C and non-G12C patients. Clinical trial information: NCT02642042. [Table: see text]

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Crossref · 10.1200/jco.2019.37.15_suppl.9021

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  • Another phase II study with KRAS-mutant NSCLC (n=54, including 19 with G12C, 9 with G12D, 9 with G12A) documented a trend toward worse PFS (HR=1.86, p=0.06) and survival (HR=1.80, p=0.14) in G12C patients compared to non-G12C patients.

    “Another phase II study with KRAS-mutant NSCLC (n = 54, including 19 with G12C, 9 with G12D, 9 with G12A) documented a trend toward worse PFS (HR = 1.86, p = 0.06) and survival (HR = 1.80, p = 0.14) in G12C patients compared to non-G12C patients (50).”

    From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [50]

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Authors
Gadgeel, S. M., Miao, J., Riess, J. W., Mack, P. C., Gerstner, G. J., Burns, T. F., Taj, A., Akerley, W. L., Dragnev, K. H., Moon, J., Gandara, D. R., & Kelly, K.
Affiliations
  • University of Michigan (US)
  • Fred Hutch Cancer Center (US)
  • UC Davis Comprehensive Cancer Center (US)
  • Illinois CancerCare (US)
  • UPMC Hillman Cancer Center (US)
  • St Marys of Michigan, Saginaw, MI;
  • University of Utah (US)
  • Dartmouth–Hitchcock Medical Center (US)
  • SWOG Cancer Research Network (US)
  • University of California, Davis (US)
ORCID
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2019-05-20
Volume
37
Issue
15_suppl
Pages
9021-9021
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2019.37.15_suppl.9021
OpenAlex
W2946878611
Cited by
15
References
0
Citations by year
2024: 1 · 2021: 10 · 2020: 3 · 2019: 1
Type
conference abstract
Language
en
Open access
closed
Locations
Journal of Clinical Oncology (publishedVersion)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
docetaxel, trametinib, KRAS G12C mutation, recurrent NSCLC, MEK inhibitors, combination chemotherapy, TP53 mutation, LKB1 mutation, progression-free survival, overall survival, response rate, predictive biomarkers, treatment toxicity, liver metastasis

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