Download Sumitra Thongprasert, MD

Ongoing Lung Cancer Research in Asia
Sumitra Thongprasert, MD
Objectives
• Provide an overview of the current state of lung cancer research in Asia
• Discuss current key issues and challenges
• Discuss potential changes and future directions
Number of new cases (million)
Lung Cancer Is the Most Common Cancer Globally
16
14
Incidence of new cases of cancer*
14.1
12
10
8
6
4
2
1.8
1.7
1.4
1.1
1.0
0.8
0.5
0
• Account for ≈13% of all cancer diagnosed
*Globocan Data, 2012; **Excluding non-melanoma skin cancer.
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx#. Accessed January 25, 2015.
0.5
0.4
0.4
Lung Cancer Is the Most Common Cause of Death from Cancer Globally
Total cancer mortality*
Prostate,
Breast, 6.4% 3.7%
Others
combined,
31.6%
Lung,
19.4%
NHL,
2.4%
Bladder, 2%
CRC,
8.5%
Liver, 9.1%
Stomach,
8.8%
Cervix, 3.2%
Oesophagus,
4.9%
• Responsible for nearly 1 in 5 cancer deaths (1.59 million or 19.4% of total)
*Globocan Data, 2012.
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx#. Accessed January 25, 2015.
Incidence of Lung Cancer in Asia
Incidence of lung cancer
Percentage of total new cases
New cases of lung
cancer (million)
3.0
2.5
2.0
Asia
Rest of the world
1.8
1.5
1.1
42.8%
57.2%
1.0
0.5
0
Global
Asia
• Asia accounts for the majority of the new cases of lung
cancer diagnosed in the world
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx#. Accessed January 25, 2015.
Number of new cases (million)
Mortality of Lung Cancer in Asia
3.0
Mortality of lung cancer
Percentage of total lung
cancer mortality
2.5
2.0
1.59
1.5
0.94
1.0
59.1%
40.9%
0.5
0
Global
Asia
• Asia accounts for the majority of lung cancer mortality in the
world
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx#. Accessed January 25, 2015.
Lung Cancer Incidence and Mortality for
Select Asian Countries
New cases
Number of cases (thousand)
700
600
Mortality
652.8
597.2
500
400
300
200
94.9 75.1
100
70.3 63.8
22.9 17.8
19.5 17.7
12.1 10.4
South Korea
Thailand
Philippines
0
China
Japan
India
http://globocan.iarc.fr/Pages/fact_sheets_population.aspx#. Accessed January 25, 2015.
DRIVER MUTATIONS
Key Driver Mutations in Select Asian Populations:
China and Japan
1
2
Japan
EML4ALK
5%
MET
4%
ErbB2 BRAF
3%
1%
Unknown
22%
EGFR
50%
KRAS
15%
1. Wu YL et al. Ann Oncol. 2011;22(suppl 9). Abstract 33.
2. Mitsudomi T. Jpn J Clin Oncol. 2010;40:101-6.
Genetic Variations and Driver Mutations:
East Asian vs Western Population
Genes
Western/ADC
n/N (%)
Western/SCC
n/N (%)
Asian/ADC
n/N (%)
Asian/SCC
n/N (%)
TP53
164/532 (30.8)
62/113 (54.9)
325/978 (33.2)
64/179 (35.8)
EGFR
940/4890 (19.2)
113/334 (3.3)
1492/3117 (47.9)
22/474 (4.6)
KRAS
613/2352 (26.1)
12/187 (6.4)
236/2114 (11.2)
5/284 (1.8)
LKB1
99/610 (16.2)
13/137 (9.5)
22/550 (4.0)
0/166 (0.0)
EML4-ALK
55/856 (6.4)
4/89 (4.5)
71/1326 (5.4)
5/277 (1.8)
PTEN
25/419 (6.0)
0/12 (0.0)
4/248 (1.6)
12/123 (9.8)
BRAF
66/2028 (3.3)
1/408 (0.2)
5/321 (1.6)
0/124 (0.0)
PIK3CA
6/475 (1.3)
1/71 (1.4)
4/235 (1.7)
8/124 (6.5)
ErbB2
7/505 (1.4)
2/117 (1.7)
20/712 (2.8)
1/259 (0.4)
ADC = adenocarcinoma; SCC = squamous cell carcinoma.
Dearden S et al. Ann Oncol. 2013;24:2371-6.
CLINICAL DEVELOPMENT IN LUNG
CANCER IN ASIA
Asia’s Contribution to the Advancement of Treatment for
NSCLC
• Establishment of the efficacy of
EGFR-targeted TKIs in patients
with EGFR mutation–positive
patients1-5
1. Maemondo M et al. N Engl J Med. 2010;362:2380-8.
2. Mitsudomi T et al. Lancet Oncol. 2010;11:121-8.
3. Mok TS et al. N Engl J Med. 2009;361:947-57.
4. Zhou C et al. Lancet Oncol. 2011;12:735-42.
5. Fukuoka M et al. J Clin Oncol. 2011;29:2866-74.
6. Soda M et al. Nature. 2007;448:561-6.
• Identification of EML4-ALK
fusion protein as a targetable
driver mutation in the treatment
of NSCLC by Soda M et al in
20076
Asia in the Development of Novel Targeted Agents in the
Treatment of Lung Cancer
Select phase 3 first-line Asian lung cancer trials:
• NEJ002 (gefitinib vs carboplatin + paclitaxel, N=228)
• WJTOG3405 (gefitinib vs cisplatin + docetaxel, N=177)
• IPASS (gefitinib vs carboplatin + paclitaxel; N=1217*)
• OPTIMAL/CTONG-0802 (erlotinib vs gemcitabine + carboplatin,
N=165)
• ENSURE (erlotinib vs cisplatin + gemcitabine, N=217)
• FASTACT-2 (erlotinib + gemcitabine + carboplatin → erlotinib
maintenance vs gemcitabine + carboplatin → placebo, N=451)
• LUX-Lung 6 (afatinib vs cisplatin + gemcitabine, N=324**)
*Non-selected patients in terms of EGFR status.
**EGFR activating mutation positive patients.
1. Maemondo M et al. N Engl J Med. 2010;362:2380-8; 2. Mitsudomi T et al. Lancet Oncol. 2010;11:121-8;
3. Mok TS et al. N Engl J Med. 2009;361:947-57; 4. Zhou C et al. Lancet Oncol. 2011;12:375-42;
5. Wu YL et al. J Thoracic Oncol. 2013;8(suppl 2):S603; 6. Wu YL et al. Lancet Oncol. 2013;14:777-86;
7. Wu YL et al. Lancet Oncol. 2014;15:213-22.
Asia in the Development of Novel Targeted Agents in the
Treatment of Lung Cancer
Select phase 3 global lung cancer trial with study sites in Asia:
First-line:
• LUX-Lung 3 (afatinib vs pemetrexed + cisplatin, N=345; 249 Asian)
• PROFILE 1014 (crizotinib vs pemetrexed + cisplatin or carboplatin, N=343;
157 Asian)
Maintenance:
• SATURN (erlotinib vs placebo, N=889; 131 Asian)
Second-line:
• PROFILE 007 (crizotinib vs pemetrexed or docetaxel, N=347; 157 Asian)
• Titan (erlotinib vs platinum doublet, N=424; 54 Asian)
• REVEL (ramucirumab + docetaxel vs docetaxel, N=1253; 160 Asian)
• LUME-Lung 1 (N=1314; 239 Asian)
1. Sequist LV et al. J Clin Oncol. 2013;31:3327-34; 2. Solomon BJ et al. N Engl J Med. 2014;371:2167-77;
3. Cappuzzo F et al. Lancet Oncol. 2010;11:521-9; 4. Shaw AT et al. N Engl J Med. 2013;368:2385-94;
5. Ciuleanu T et al. Lancet Oncol. 2012;13:300-8; 6. Garon EB et al. Lancet. 2014;384:665-73;
7. Reck M et al. Lancet Oncol. 2014;15:143-55.
ONGOING CLINICAL TRIALS IN LUNG
CANCER IN ASIA
Ongoing Lung Cancer Clinical Trials in Asia
300
266
Number of trials
250
201
200
150
100
64
50
0
Total
NSCLC
SCLC
Including all study phases and observational, diagnostic, and staging studies.
Statistics from WHO “International clinical trials registry platform” for trials registered in 2014: http://apps.who.int/trialsearch/AdvSearch.aspx.
Accessed January 26, 2015.
Ongoing NSCLC Clinical Trials in Select
Asian Countries*
250
200
201
150
93
100
50
50
34
24
0
Total
Japan
China
Korea
Taiwan
*Some of the clinical trials are conducted in multiple Asian countries.
Statistics from WHO “International clinical trials registry platform” for trials registered in 2014: http://apps.who.int/trialsearch/AdvSearch.aspx.
Accessed January 26, 2015.
Ongoing Phase 3 NSCLC Clinical Trials in China, Japan, Korea, and Taiwan
Total (including multinational and country-specific trials)
Country-specific trials only
Number of cases (thousand)
16
14
14 *
14 **
14 ^
13
#
12
10
8
6
4
4
3
2
0
0
Japan
China
Korea
0
Taiwan
*3 out of 14 conducted only in Japan; **4 out of 14 conducted only in China; ^none conducted only in Korea; #none
conducted only in Taiwan.
Statistics from WHO “International clinical trials registry platform” for trials registered in 2014: http://apps.who.int/trialsearch/AdvSearch.aspx.
Accessed January 26, 2015.
KEY ISSUES AND CHALLENGES
Key Issues/Challenges
• Large disparity exists between highly developed and
developing/underdeveloped countries in Asia
• Issues/challenges, particularly associated with developing/
underdeveloped countries
– Smoking epidemic
– Air pollution
– Lack of disease awareness, robust prevention initiatives, and
early screening
– Inequality in access to quality care/access to clinical trials (rural
vs urban)
– Inadequate cancer health care infrastructure
– Need for more and better-educated health care professionals
– Alternative or traditional approaches to treatment (eg, China and
India)
FUTURE DIRECTIONS
Important Initiatives Needed to Improve Patient Care
• Education and public awareness campaigns on the
importance of lifestyle modifications, screening, and early
detection/intervention in disease management
• Increased governmental support and investment in health
care infrastructure/additional resources to ensure more
equitable access to care for all segments of the population
• Increased funding to train more health care providers to
serve underprivileged populations, particularly in rural
areas
• Increased collaboration between academic centres and the
private sector, including pharmaceutical companies, to
promote basic scientific research and expedite the
development of effective therapies for cancers that are
prevalent in Asia
Summary
• Lung cancer is highly prevalent in Asia, accounting for the
majority of new cases diagnosed and responsible for the most
cancer-related mortality in the world
• The Asia Pacific region has made important contributions to
the advancement of the current treatment of lung cancer and
continues to be a key area for research and clinical
development
• However, a number of serious issues and challenges remain
• Significant governmental support and investment as well as
increased collaboration with the private sector are needed to
improve disease management/patient care