Virtual Library
Start Your Search
F. Ohyanagi
Author of
-
+
MINI 07 - ChemoRT and Translational Science (ID 110)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:D. Raben, B. Kavanagh
- Coordinates: 9/07/2015, 16:45 - 18:15, 201+203
-
+
MINI07.01 - A Randomized Phase II Study of S-1 and Cisplatin vs Vinorelbine and Cisplatin with Concurrent Radiotherapy for Locally Advanced NSCLC: WJOG5008L (ID 544)
16:45 - 18:15 | Author(s): F. Ohyanagi
- Abstract
- Presentation
Background:
Cisplatin-based chemotherapy and concurrent radiotherapy is the standard treatments for locally advanced non-small cell lung cancer ( LA-NSCLC). This trial evaluated two experimental regimens of chemotherapy with concurrent radiotherapy.
Methods:
Eligible patients (pts) with unresectable stage III NSCLC, 20 to 74 years of age, and ECOG PS of 0–1 were randomized to either Arm SP, S-1 (40 mg/m[2]/dose per oral, b.i.d, on days 1-14) and cisplatin (60 mg/m[2] on day 1) repeated every 4 weeks or Arm VP, vinorelbine ( 20mg/m[2] on day 1, 8) and cisplatin (80 mg/m[2] on day) repeated every 4 weeks with early concurrent thoracic radiotherapy of 60Gy at 2 Gy per daily fraction. The primary endpoint was overall survival rate at 2-year (2yr-OS). A pick-the-winner design was used to identify the treatment regimen most likely to be superior. The planned sample size was 55 patients per arm, assuming in each arm that the null hypothesis for 2yr- OS was 50% versus an alternative hypothesis for 65% with one-sided alpha of 0.10 and power of 80%. All the radiation treatment plans were reviewed at quality assurance committee meetings. (Study ID: UMIN000002420)
Results:
One hundred eleven patients were registered between Sep 2009 and Sep 2012. Of 108 patients for efficacy analysis, the 2yr-OS was 76% (95% CI, 62-85%) for SP and 69% (95% CI, 54-79%) for VP. The hazard ratio (HR) of death between the two arms was 0.85 (0.48-1.49). The median progression-free survival (PFS) was 14.8 months for SP and 12.3 months for VP with a HR of 0.92 (0.58-1.44). 80% and 48% of pts completed the protocol treatment in SP and VP, respectively. Common grade 3-4 toxicities of both SP and VP were neutropenia 33%, 75%, platelets 9%, 4%, hemoglobin 26%, 28%, febrile neutropenia 9%, 17%, diarrhea 6%, 0% respectively. There were 4 and 5 treatment-related deaths in Arms SP and VP, respectively. The quality assurance committee judged that 74% of radiation treatment plans had no deviation and 24% had a minor deviation.
Conclusion:
Both arms rejected the null hypothesis for 2yr-OS. In this study Arm SP was declared the winner in terms of 2yr-OS, PFS, treatment completion, and toxicity.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MINI 10 - ALK and EGFR (ID 105)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T. Yap, T. Li
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
-
+
MINI10.10 - A Multicenter Prospective Biomarker Study in Afatinib-Treated Patients with EGFR-Mutation Positive Non-Small Cell Lung Cancer (ID 472)
16:45 - 18:15 | Author(s): F. Ohyanagi
- Abstract
- Presentation
Background:
Afatinib is an oral, irreversible ErbB family blocker and one of the key drugs for patients with EGFR mutation positive advanced non-small cell lung cancer (NSCLC). Although treatment with afatinib has a clinical benefit for these patients, such individuals inevitably develop drug resistance as with other TKIs. This is a multicenter prospective biomarker study to inform the usefulness of noninvasive liquid biopsy in the treatment of EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and explore the molecular mechanism of acquired-resistance against afatinib.
Methods:
Eligible patients were EGFR-TKIs naïve and had histologically and cytologically confirmed stage IIIB/IV adenocarcinoma of the lung with activating EGFR mutations. Patients remained on afatinib treatment until disease progression or unacceptable toxicity. Tumor samples were collected upon before afatinib treatment and after disease progression. Plasma samples were collected upon before and during afatinib treatment (4 and 24 weeks after initiation) and after disease progression. DNA derived both from tumors and plasma was analyzed using Scorpion-ARMS (ARMS), digital PCR (dPCR) and next generation sequencing (NGS). We used a nanofluidic dPCR system (BioMark HD System; Fluidigm) with a digital chip to detect activating or resistance mutations of EGFR in a quantitative and highly sensitive manner. NGS on an Ion Torrent PGM device (Thermo Fisher Scientific) was applied to detect target molecules which contribute to the survival and growth of lung cancer cells. We compared the sensitivity of these methods in detection of EGFR activating mutations in plasma DNA.
Results:
A total of 35 EGFR mutation positive NSCLC patients were enrolled. Twenty one patients harbored a deletion in exon 19 and fourteen patients had an L858R missense mutation in exon 21. Twenty seven (77.1%) patients had an objective response. In plasma DNA obtained before afatinib treatment, dPCR and NGS detected EGFR activating mutations more sensitively compared with ARMS (83.9% v 58.1%; p <0.005, 74.2% v 58.1%; p =0.059, respectively). Concordance of EGFR activating mutations detected by dPCR and NGS was 26/31 (84%) (kappa value: 0.52). All of the mutation type detected by NGS on plasma DNA completely corresponded to that found in matching tumor tissue by NGS. As of March 2015, serial plasma DNA was analyzed in 9 patients. The copy number of activating mutation was markedly decreased in 5 of 9 patients.
Conclusion:
EGFR activating mutations in plasma DNA were frequently detected by dPCR or NGS. We will present the detailed data for monitoring mutation load in plasma DNA during the afatinib treatment.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
