2017年7月28日 日本臨床腫瘍学会総会2日目(神戸市)
AJ-1の講演内容を見ると、欧米と日本でのドラッグ・ラグはだいぶん是正されてきた様子。
ASCO / JSMO Joint Symposium
AJ-1:
Expanding the Reach of Targeted Therapy in Lung Cancer
<EGFR>(in USA, 15% of all NSCLC)
・EGFR mutationとEGFR阻害薬の効果が相関していることの発見
・NEJ-002試験がpositiveとなった
→gefitinibは日本で2002年に承認、米国では2015年まで待たなければならなかった
・Afatinibは日本では2013年に承認、米国では2014年に承認
・real worldにおけるEGFR阻害薬の効果
→日本では生存期間中央値は30.8ヶ月(Inoue et al., Jpn J Clin Oncol 2016)
https://www.ncbi.nlm.nih.gov/pubmed/26977054
→米国では生存期間中央値は30.9ヶ月(Liu et al., J Thorac Oncol 2016)
<ALK>(in USA, 5% of all NSCLC)
・PROFILE 1014, crizotinib
日本では2012年に承認、米国では2013年に正式承認
・J-ALEX study, Hida et al., Lancet 2017, Alectinib
日本では2014年に承認、米国では2015年に承認
<ROS1>(in USA, 1% of all NSCLC)
・Shaw et al., N Engl J Med, 1963-, 2017
Crizotinibが有効、日本では2017年に承認、米国では2016年に承認
<BRAF>(in USA, 1% of all NSCLC)
・BRF 113948 study, Planchard et al., Lancet Oncol 2016, 984-993
→https://www.ncbi.nlm.nih.gov/pubmed/27283860
ORR 64%, mPFS 9.7M
Dabrafenib+Trametinibが有効、米国では2017年に承認
<others>
・MET exon 14 skipping mutation
・NTRK
・RET
・development medication for rare cancers
Single arm studyで、PFS 9-10ヶ月以上が承認のための相場
AJ-2:
Development of Nationwide Genomic Screening Project ( LC-SCRUM-Japan ) for the Establishment of Cancer Precision Medicine
・From Histology to Molecular Target for Decision Making
In Japan, EGFRm 53%, KRASm 9.4%, ALKr 3.8%
・At the beginning of LC-SCRUM pfoject, only RETr, ALKr and ROS1r are screened for confirmed EGFRm negative patients
→If RETr(+), recommend to entry LURET study, investigator initiated trial.
・Crizotinib for ROS1r(+) NSCLC for East-Asian population: ASCO 2016 abst.#9022
・Overall survival analysis in LC-SCRUM participant
N=1,147
Driver mutation(+) and Targeted Therapy(+): n=123: mOS 44.2M ( 30M ? not reached )
Driver mutation(+) and Targeted Therapy(-): n=450: mOS 29.3M ( 24.4M ? 49.9M )
Driver mutation(-): n=574: mOS 30.6M ( 26.5M ? 48.6M )
AJ-3:
Combination Therapy with Molecularly Targeted Agents in Lung Cancer
・EGFRm(+) patients survival in “Real World” Japan
5-year OS rate: 21.5% ( overall n=1,657) and 13.8% ( stage IV patients only )
Median OS: 29.7M ( 28.1M ? 31.4M )
Upfront chemotherapy may be related to higher 5-year OS rate.
Upfront chemotherapy may be related to longer chemotherapy period.
→Maybe there are selection biases.
・concurrent chemotherapy and TKI
Randomized phase II NEJ005 updated data: mOS 41.9M vs 30.7M
→Oizumi et al., ASCO 2017 abst.#9038
→Randomized phase III NEJ009 ongoing ( accrual finished, follow up ongoing )
・intercalated gefitinib phase II study: mOS 48M
→Kanda et al., Lung Cancer. 2015 Sep;89(3):287-93
→https://www.ncbi.nlm.nih.gov/pubmed/26169499
・Erlotinib + Bevacizumab therapy
JO25567 study ( phase II )
NEJ026 study ( phase III, accrual finished )
・RELAY study
Erlotinib + Bevacizumab vs Erlotinib ( phase III study, primary endpoint:PFS )
・FLAURA study press released as “positive” on 27 / 07 / 2017
・WJOG8715L: Osimertinib + Bevacizumab phase II
・J-SONIC trial: NSCLC with IPF patientsにChemotherapy + nintedanib
・座長からの要請事項:real world’s EGFRm NSCLC患者について、今後も長期フォローした方がいいのでは?
AJ-4:
Current Status of Liquid Biopsy in Lung Cancer
・Liquid Biopsy is…
→non ? invasive genomic diagnostic tool, Oxnard et al., Clin Cancer Res 2014
→drug resistance monitoring tool
→pharmacodynamics research tool
・positive predictive value ( PPV ):
100% for EGFRm detection
100% for KRASm detection
79% for T790M detection
・Sensitivity
82% for Exon 19 deletion detection
72% for Exon 21 point mutation detection
77% for T790M resistance detection
64% for KRASm detection
→Sacher et al., JAMA Oncol. 2016 Aug 1;2(8):1014-22
→https://www.ncbi.nlm.nih.gov/pubmed/27055085
・Plasma genotyping and Tissue genotyping
T790M confirmed from Tissue → well correlated to PFS
T790M confirmed from Plasma → not well correlated to PFS
→Oxnard et al. J Clin Oncol 2016
・ctDNA monitoring by NGS assay
26人のOsimertinib resistant patients
9人がT790M(+)で、そのうち6人がC797S(+), 3人がC797S(-)
17人がT790M(-)で、4人が小細胞癌転化、MET異常が3人、BRAF異常が1人、KRASmも1人