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Taishi Harada
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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): Taishi Harada
- 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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P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.03-13 - Acquired Resistance to Afatinib in Non-Small Cell Lung Cancer with EGFR G719X Mutation (Now Available) (ID 1057)
10:15 - 18:15 | Presenting Author(s): Taishi Harada
- Abstract
Background
The frequency of EGFR mutations is said to be relatively high within East Asian population. The most common EGFR mutations such as exon 19 deletions and exon 21 L858R mutation are strong predictors of good response to EGFR-TKIs in non-small-cell lung cancer. Exon 20 T790M mutation which accounts for a large part of 1st and 2nd generation EGFR-TKI resistance, is well known to be detected after failure of prior EGFR-TKI therapy. Furthermore, T790M mutation is a predictor of good response to osimertinib, 3rd generation EGFR-TKI. Meanwhile, other uncommon EGFR mutations are identified, such as exon 18 G719X mutation, exon 20 S768I mutation, and exon 21 L861Q mutation. LUX-Lung study reported afatinib may be effective for these uncommon EGFR mutations, however, their treatments are still controversial and their resistance-gaining mechanisms to EGFR-TKI are also unknown.
Method
We evaluated the characteristics of patients with G719X single mutation and their effectiveness of afatinib treatment. Furthermore, we analyzed the mechanism of acquired resistance to afatinib from their re-biopsied samples.
Result
Eighteen patients had G719X single mutation, which include fifteen patients with smoking history. Of all patients with G719X mutation, ten patients were treated with afatinib, which response rate was 40% (4/10). Eight patients of those treated with afatinib underwent re-biopsy after failure of the therapy, and their results revealed that G719X mutation was disappeared in six samples, and T790M mutation was not detected after afatinib treatment.
Conclusion
As previously reported, the presence of G719X mutation might be used as a predictor of sensitivity to afanitib therapy. Our data suggest that the loss of cancer cells with G719X mutation could be the main mechanism of acquired resistance to afanitib. Furthermore, patients with smoking history were seen frequently in those with G719X mutation. Considering that G719X mutation negative cancer cells may coexist with G719X mutation positive cells in NSCLC patients, smoking might be associated with development of its heterogeneity.
