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Yuki Akazawa
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-13 - A Phase 2 Trial Assessing Osimertinib Activity Against Leptomeningeal Carcinomatosis in EGFR-Mutant Lung Cancer (Now Available) (ID 470)
08:00 - 18:00 | Presenting Author(s): Yuki Akazawa
- Abstract
Background
Leptomeningeal carcinomatosis (LMC) occurs in 10 % of EGFR-mutant lung adenocarcinoma (LA). Retrospective studies have suggeted a clinical benefit of osimertinib in treating LMC in patients with EGFR-mutant LA. We conducted a phase 2 prospective trial to demonstrate the clinical efficacy, activity, and LMC-specific mechanisms of resitance to osimertinib in EGFR-mutant LA patients.
Method
We performed gadalidium-enhanced brain MRIs at the time of enrollment, followed by scheduled brain imaging once every six weeks. Clinical neurological exams were performed every four weeks. Adverse Events (AEs) were assessed by NCI-CTCAE Ver. 4. Cerebral spinal fluid (CSF) and plasma was obtained on day 1 and 21 for all patients. The CSF osimertinib penetration rate was measured by liquid-chromatography mass spectrometry (LC-MSMS) and compared to plasma osimertinib levels. Targeted droplet digital PCR (ddPCR) was used to detect copy number changes of Met and the EGFR C797S mutation in patients CSF-DNA and plasma cell free (cf) DNA.
Result
We enrolled six pre EGFR-TKI treated EGFR mutant LA with LMC. We observed a LMC-specific progression free survival of 3.7 months and overall survival of 6.2 months or longer with osimertinib. Four and three of six patients showed neurological and radiological responses, respectively. No patients had any AEs greater than grade 3 and all patients continued osimertinib beyond PD. The osimertinib CSF penetration rate was 1.2±0.5%. Met copy number was normal in plasma, but increased in the CSF of 2/6 patients prior to progression. Met copy number was confirmed in 1/6 patients at the time of progression. An aquired EGFR C797S mutation was observed in 1/6 patients prior to progression.
Conclusion
Osimertinib 80 mg is efficacious in the treatment of LMC in EGFR mutated LA. CSF-specific MET copy number gain and EGFR C797S mutations arise prior to progression in EGFR-mutant LA patients treated with osimeritinib.
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MA03 - Clinomics and Genomics (ID 119)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Heather A Wakelee, Wilfried Ernst Erich Eberhardt
- Coordinates: 9/08/2019, 10:30 - 12:00, Colorado Springs (1994)
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MA03.11 - Chemotherapy After PD-1 Inhibitors Versus Chemotherapy Alone in Patients with Non–Small Cell Lung Cancer (WJOG10217L) (Now Available) (ID 409)
10:30 - 12:00 | Author(s): Yuki Akazawa
- Abstract
- Presentation
Background
Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response in patients with non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of subsequent chemotherapy after PD-1 inhibitors (CAP) compared with chemotherapy alone.
Method
We conducted a multicenter retrospective cohort study for patients with advanced or recurrent NSCLC who were treated at 47 institutions across Japan between 1 April 2014 and 31 July 2017 with chemotherapy (docetaxel with or without ramucirumab; S-1; or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort). The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors, including age, sex, smoking status, performance status, histology, EGFR or ALK genetic alterations, brain metastasis, and recurrence after curative radiotherapy.
Result
A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology, EGFR or ALK alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 10.8% for the control cohort (ORR ratio, 1.75; 95% confidence interval [CI], 1.25–2.45; P = .001). Median PFS was 3.5 and 2.6 months for the CAP and control cohorts, respectively (hazard ratio [HR], 0.862; 95% CI, 0.743–0.998; P = .048). The PFS rate at 3, 6, and 12 months was 53.3%, 28.5%, and 4.6%, respectively, for the CAP cohort, and 44.3%, 19.7%, and 6.1% for the control cohort. Median OS was 9.8 months for the CAP cohort and 10.3 months for the control cohort (HR, 0.979; 95% CI, 0.813–1.179; P = .822).
Conclusion
After adjustment for selection bias using propensity score–weighted analysis, CAP showed a significantly higher ORR and longer PFS compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into an OS advantage, and no PFS benefit was apparent at 12 months despite the improvement observed at 3 and 6 months. Our findings suggest that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.
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