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Published on: September 8, 2017
Brain metastases in clinical trial participants with KRAS-mutated advanced non-small cell lung cancer receiving
Jacob Aptekar1, Rahul Jain1, Beata Korytowsky2
1Medidata, a Dassault Systèmes Company, New York, NY, USA.
Objectives:
Limited data are available on central nervous system (CNS) efficacy with standard-of-care therapies for KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC treated with docetaxel using pooled data from historical clinical trials.
Materials And Methods:
Data from phase 2/3 trials of docetaxel-containing regimens in advanced NSCLC were sourced from the Medidata platform. Analysis was restricted to stage IIIB-IV KRASmut NSCLC with disease progression after ≥ 1 systemic anticancer therapy. Participants with asymptomatic, treated, and stable brain metastases were included. Endpoints included 12-month CNS disease control rate (CNS-DCR) and CNS progression per Response Evaluation Criteria in Solid Tumors; progression-free survival (PFS); and overall survival (OS). Data were pooled and analyses stratified by baseline brain metastases status.
Results:
A total of 595 participants were included in the analysis (62 [10%] with baseline brain metastases and 533 [90 %] without). Among participants with brain metastases, 17 (27.4 %) had CNS progression during docetaxel treatment and 12-month CNS-DCR was 75.8 %; 45 (8.4 %) participants without baseline brain metastases developed brain metastases during treatment. In an analysis restricted to patients with metastatic disease, outcomes with and without baseline brain metastases included: median PFS, 3.3 and 4.9 months (p < 0.005); 12-month PFS, 5 % and 16 %; median OS, 6.9 and 10.4 months (p < 0.005); and 12-month OS, 20 % and 44 %, respectively.
Conclusion:
These findings establish CNS progression rates with docetaxel in previously treated KRASmut advanced NSCLC and facilitate interpretation of data from ongoing randomized clinical trials of novel KRAS-targeted therapeutic strategies vs. docetaxel.
Insights
Docetaxel treatment showed a 27.4% central nervous system (CNS) progression rate in KRAS-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. This study provides crucial data for evaluating new KRAS-targeted therapies.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Limited data exist on central nervous system (CNS) efficacy for standard-of-care therapies in KRAS-mutated (KRASmut) advanced non-small cell lung cancer (NSCLC).
- Brain metastases are a significant concern in advanced NSCLC, impacting patient outcomes.
Purpose of the Study:
- To investigate the incidence and progression of brain metastases in KRASmut advanced NSCLC patients treated with docetaxel.
- To pool data from historical clinical trials to assess CNS efficacy.
Main Methods:
- Pooled analysis of phase 2/3 trials involving docetaxel-containing regimens in advanced NSCLC.
- Inclusion of patients with stage IIIB-IV KRASmut NSCLC who progressed after at least one systemic therapy.
- Analysis focused on participants with asymptomatic, treated, or stable brain metastases, assessing 12-month CNS disease control rate (CNS-DCR), CNS progression, progression-free survival (PFS), and overall survival (OS).
Main Results:
- Out of 595 participants, 62 (10%) had baseline brain metastases, and 533 (90%) did not.
- Among those with baseline brain metastases, 27.4% experienced CNS progression, with a 12-month CNS-DCR of 75.8%.
- 8.4% of participants without baseline brain metastases developed them during treatment. Patients with baseline brain metastases had significantly shorter median PFS (3.3 vs. 4.9 months) and OS (6.9 vs. 10.4 months) compared to those without.
Conclusions:
- Docetaxel treatment is associated with CNS progression rates of 27.4% in previously treated KRASmut advanced NSCLC patients with brain metastases.
- These findings are essential for interpreting ongoing clinical trials comparing novel KRAS-targeted therapies with docetaxel.
