OPTIMAL
Lung cancer &
EGFR activating mutations
• Lung cancer is the most common cancer and one of the deadliest diseases
worldwide:
– 1.35 million new cases diagnosed every year 1
– Responsible for 1.18 million deaths each year 1
– Each day, more than 3,000 people die from lung cancer, equal to two deaths
every minute 2
• Lung cancer with EGFR activating mutations is a distinct form of cancer
• As many as one in three (30%) Asian patients and an estimated one in ten
(10%) lung cancer patients in the Western population have NSCLC with
EGFR activating mutations 3,4
1. Parkin DM. Global lung cancer statistics, 2002. CA Cancer J Clin (2005). 55. 74 – 108
2. 1.18 million deaths per year / 365 days = 3,232 deaths per day - 1.18 million deaths per year / 365
days – 3,232 deaths per day / 24 hours = 134 deaths per hour/60 minutes = 2.24 deaths per minute
3. Rosell R, Moran T, Queralt C, et al. N Engl J Med 2009;361:958–67.
4. Mitsudomi T, Kosaka T, Yatabe Y. Int J Clin Oncol 2006;11:190–8.
Activating mutations occur in the area of
EGFR where Tarceva is active
Chromosome 7
EGFR transcript
EGFR protein
Exons 1–16
EGFR
Cell membrane
Exon 17
Activating mutations
in Exons 18–24
Tyrosine –
kinase domain
Exons 25–28
Tarceva binds in this area
Tarceva in NSCLC with EGFR activating
mutations – phase III OPTIMAL study design
Tarceva
 Chemonaïve
 Advanced NSCLC
 EGFR activating mutations
R
1:1
165 patients
Chemotherapy
[gemcitabine and carboplatin]
Primary endpoint
•
Progression-free survival (PFS)
Secondary endpoints include
•
Overall survival (OS)
•
Objective response rate
•
Time to disease progression
•
Duration of response
•
Safety
•
Health-related QoL (FACT-L, LCSS)
•
Exploratory biomarker analyses
FACT-L = Functional Assessment of Cancer Therapy-Lung; LCSS = lung cancer symptom scale
Patients in both groups
had similar characteristics
Tarceva
Chemotherapy
(82 patients) (72 patients)
Median age years, (range)
57 (31–74)
59 (36–78)
Age <65 yrs / ≥65 yrs (%)
77 / 23
71 / 29
Male / Female (%)
42 / 58
40 / 60
Adenocarcinoma / non-adenocarcinoma (%)
88 / 12
86 / 14
Current or former smoker / never-smoker (%)
28 / 72
31 / 69
Current = smoked >100 cigarettes in entire lifetime and are either currently smoking or quit smoking <1 year ago
Former = smoked >100 cigarettes in entire lifetime and quit smoking ≥1 year ago
Never = smoked ≤100 cigarettes in entire lifetime or never smoked
Tarceva nearly tripled time people
lived without their disease getting
worse (PFS)
1.0
Tarceva
People lived a median of 13.1
months without their
disease progressing, which is over one year
PFS probability
0.8
0.6
0.4
0.2
4.6
0
0
13.1
5
Chemotherapy
People lived a median of 4.6
months without their
disease progressing
10
15
20
Time (months)
25
HR=0.16 (0.10–0.26), p<0.0001
Translates to 84% risk reduction
Over half of all Tarceva patients were
alive and progression free at one year
1.0
Tarceva
At one year 56.9% patients were
alive without their disease
progressing
PFS probability
0.8
0.6
0.4
0.2
0
0
5
10
15
20
Time (months)
Chemotherapy
At one year 1.7% patients were
alive without their disease
progressing
25
All patient sub-groups had
better PFS with Tarceva
Overall
Female
Male
Age ≥65
Age <65
Never smoker
Current/former smoker
Adenocarcinoma
Non-adenocarcinoma
0
0.5
1.0
HR
Favours Tarceva
1.5
Favours chemotherapy
Tarceva gave patients a better tumour
response
Tarceva
Chemotherapy
82 patients
72 patients
2.4 %
0.0 %
Partial Response
80.5 %
36.1 %
Stable Disease
13.4 %
45.8 %
3.7 %
16.7 %
Overall Response Rate
82.9 %
36.1 %
p<0.00001
Disease Control Rate
96.3 %
81.9 %
p=0.002
Complete Response
Progressive Disease
Chemotherapy was associated with
more haematologic toxicity
100
80
Tarceva
Grade 1/2
Patients (%)
Grade 3/4
60
40
20
0
Chemotherapy
Grade 1/2
Grade 3/4
No unexpected adverse events were
seen with Tarceva
100
Patients (%)
80
60
40
20
0
Tarceva
Chemotherapy
Grade 1/2
Grade 1/2
Grade 3/4
Grade 3/4
Overall conclusions
• Tarceva first-line nearly triples median progression free
survival in lung cancer with EGFR activating mutations
• More than twice as many patients who received Tarceva
experienced shrinkage of their tumours compared to those
who received chemotherapy
• Benefits were observed regardless of histology, smoking
history, age, sex and stage of disease
• Tarceva was better tolerated than chemotherapy