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Hiroaki Akamatsu
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-34 - Docetaxel Plus Ramucirumab with Prophylactic PEG-G-CSF Support for Chemo-NaïVe Elderly NSCLC Patients: A Phase II Study (WJOG9416L) (ID 12400)
16:45 - 18:00 | Author(s): Hiroaki Akamatsu
- Abstract
Background
Docetaxel monotherapy is the standard of care for chemo-naïve Japanese elderly patients with advanced non-small cell lung cancer (NSCLC), according to our results of phase III trial comparing docetaxel and vinorelbine monotherapies (WJTOG9904). In a pivotal phase III study (REVEL), docetaxel plus ramucirumab demonstrated superior response rate (RR) and progression-free survival (PFS) over docetaxel monotherapy in second-line setting for advanced NSCLC. These differences in RR and PFS were translated into overall survival (OS) benefit. This evidence prompted us to investigate docetaxel plus ramucirumab for chemo-naïve elderly patients. However, in a similarly designed Japanese randomized phase II trial (JVCG trial), febrile neutropenia (FN) was observed in 34.2% of docetaxel plus ramucirumab arm. This high incidence of FN is a clinical concern when using docetaxel plus ramucirumab for elderly patients. The ASCO practice guideline recommends primary prophylactic granulocyte-colony stimulating factor (G-CSF) when the risk of FN is 20% or higher. PEGylated-G-CSF (pegfilgrastim) administered once a cycle demonstrated reduction of FN incidence in many types of cancers. Based on the above background, we considered that primary prophylactic PEG-G-CSF would be beneficial for elderly NSCLC patients who received docetaxel plus ramucirumab.
a9ded1e5ce5d75814730bb4caaf49419 Method
This is a prospective multicenter, single-arm, phase II study conducted by West Japan Oncology Group (WJOG). Main inclusion criteria includes: chemo-naïve; aged ≥75; histologically or cytologically confirmed NSCLC; ECOG PS 0/1; adequate organ functions; with measurable disease; without contraindication of ramucirumab; written informed consent; and estimated life expectancy of at least 3 months. Intravenous docetaxel (60 mg/m2, day 1) plus ramucirumab (10 mg/kg, day 1) with subcutaneous PEG-G-CSF (3.6 mg, day 2) every 3 weeks is administered until progression. Continuous docetaxel or ramucirumab monotherapy is permitted when intolerable toxicities occur but clinical benefit is obtained by each drug. The primary endpoint is objective response rate (ORR). Secondary endpoints are PFS, OS, disease control rate, and safety. We assumed that the threshold and expected ORR were 20% and 35%, respectively. Based on this, the number of patients was calculated to be 59 to provide a power of 80% with probability of one-sided type I error being 0.05. Taking ineligible patients into account, the sample size was set at 65. When the study results are promising, we plan to conduct a phase III trial to compare docetaxel plus ramucirumab with PEG-G-CSF support vs. docetaxel monotherapy for chemo-naïve elderly NSCLC patients. Clinical trial information: UMIN000030598.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
6f8b794f3246b0c1e1780bb4d4d5dc53
Section not applicable
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-18 - A Multicenter Prospective Biomarker Study to Explore Mechanisms of Afatinib Resistance Based on Digita PCR and Next-Generation Sequencing (ID 12187)
16:45 - 18:00 | Author(s): Hiroaki Akamatsu
- Abstract
Background
Afatinib is an oral irreversible blocker of ErbB-family kinases and shows a pronounced anti-tumor efficacy for advanced non–small cell lung cancer (NSCLC) positive for activating mutations of EGFR. We applied digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS) to explore mechanisms of afatinib resistance.
a9ded1e5ce5d75814730bb4caaf49419 Method
Eligible patients had advanced lung adenocarcinoma with EGFR activating mutations. Tumor and plasma samples were collected before afatinib treatment and after treatment failure with disease progression (systemic progressive disease, SPD). DNA from the samples was analyzed by dPCR and NGS.
4c3880bb027f159e801041b1021e88e8 Result
Thirty-five patients were enrolled, with a median follow-up time of 15.8 months. Among 25 patients with SPD, tumor, plasma, or both samples were available for 18, 23, and 16 individuals, respectively. dPCR and NGS detected EGFR T790M mutation in 13 (56.5%) and 11 (47.8%) of 23 plasma samples at SPD, with sensitivity and specificity compared with tumor samples being 83.3% and 70.0% (dPCR) and 50.0% and 70.0% (NGS), respectively. Applying the ratio of the number of T790M alleles to that of activating mutations (T/A) for determination of the T790M positivity improved the sensitivity and specificity of plasma analysis compared with tumor analysis to 83.3% and 100% (dPCR) and 57.1% and 100% (NGS), respectively. Among 25 patients with SPD, the T790M mutation of EGFR alone (n = 11), copy number gain (CNG) of NRAS (n = 1), CNG of MET (n = 1), CNG of EGFR plus T790M (n = 1), and CNG and E545K of PIK3CA plus T790M of EGFR (n = 1) were identified by NGS as putative resistance mechanisms against afatinib. No tumor showed transformation to small cell carcinoma. Median progression-free survival was longer in patients with than in those without T790M at SPD (15.1 versus 10.9 months, P =0.25). Median time to SPD was much longer in patients with than in those without T790M at SPD (17.9 versus 10.9 months, P =0.18).
8eea62084ca7e541d918e823422bd82e Conclusion
Assessment of T/A ratio with dPCR or NGS improved specificity of plasma analysis for determination of T790M positivity compared with tumor analysis. dPCR and NGS analysis in tumor and plasma samples shed light on exploring mechanisms of afatinib resistance.
6f8b794f3246b0c1e1780bb4d4d5dc53
