1. ARCHER 1050: First-line Dacomitinib vs Gefitinib in EGFR-Mutant Advanced NSCLC
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
NSCLC, non-small-cell lung cancer.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. First-line Dacomitinib vs Gefitinib in EGFR-Mutant Advanced NSCLC: Background
Dacomitinib: second-generation ErbB family TKI[1]
Irreversible inhibitor of EGFR/HER1, HER2, HER4
ARCHER 1017: previous single-arm phase II examination of first- line dacomitinib in pts with EGFR-mutant NSCLC[2]
ORR: 75.6%, median PFS: 18.2 mos
ARCHER 1050: current phase III analysis evaluating safety, efficacy of first-line dacomitinib vs gefitinib for pts with advanced NSCLC and an EGFR-activating mutation[3]
NSCLC, non-small-cell lung cancer; TKI, tyrosine kinase inhibitor.
1. Engelman JA, et al. Cancer Res. 2007;67: Jänne PA, et al. Lancet Oncol. 2014;15: Mok T, et al. ASCO Abstract LBA9007.
Slide credit: clinicaloptions.com

3. ARCHER 1050: Study Design
Multicenter, randomized, open-label phase III study
Primary endpoint: PFS by blinded independent review
Secondary endpoints: PFS by investigator assessment, ORR, DoR, TTF, OS, safety, pt-reported outcomes
Stratified by race (Asian vs non-Asian),
EGFR mutation (exon 19 vs 21)
Dacomitinib 45 mg PO QD
(n = 227)
Treatment-naive pts with advanced NSCLC, EGFR-activating mutation(s), and ECOG PS 0/1; no CNS metastases or prior TKIs
(N = 452)
Gefitinib 250 mg PO QD
(n = 225)
CNS, central nervous system; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; NSCLC, non-small-cell lung cancer; PS, performance status; TKI, tyrosine kinase inhibitor; TTF, time to treatment failure.
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

4. ARCHER 1050: Baseline Characteristics
Dacomitinib
(n = 227)
Gefitinib
(n = 225)
Median age, yrs (range)
< 65 yrs, n (%)
62 (28-87)
133 (58.6)
61 (33-86)
140 (62.2)
Female, n (%)
146 (64.3)
125 (55.6)
Race, n (%)
Asian
White
Black
170 (74.9)
56 (24.7)
1 (0.4)
176 (78.2)
49 (21.8)
ECOG PS, n (%) 1
75 (33.0)
152 (67.0)
62 (27.6)
163 (72.4)
Characteristic, n (%)
Dacomitinib
(n = 227)
Gefitinib
(n = 225)
Smoking status
Never
Former
Current
147 (64.8)
65 (28.6)
15 (6.6)
144 (64.0)
62 (27.6)
19 (8.4)
EGFR mutation status
Exon 19 del
L858R
134 (59.0)
93 (41.0)
133 (59.1)
92 (40.9)
ECOG, Eastern Cooperative Oncology Group; PS, performance status.
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

5. ARCHER 1050: PFS by Independent Review
Outcome
Dacomitinib
(n = 227)
Gefitinib
(n = 225)
Median PFS, mos (95% CI)*
14.7
( )
9.2
( )
24-mo PFS, %
30.6
9.6
PFS Analysis by Subgroup n
HR (95% CI)†
All pts
452
0.58 ( )
< 65 yrs of age
≥ 65 yrs of age
273
179
0.51 ( )
0.69 ( )
Male
Female
181
271
0.72 ( )
0.50 ( )
ECOG PS 0
ECOG PS 1
137
315
0.65 ( )
0.56 ( )
Asian
Non-Asian
346
106
0.51 ( )
0.89 ( )
Never smoker
Former/current smoker
291
161
0.51 ( )
0.72 ( )
Exon 19 del in EGFR
L858R in EGFR
267
185
0.55 ( )
0.63 ( )
*HR: 0.59 (95% CI: ; P < .0001)
Median follow-up for PFS: mos
ECOG, Eastern Cooperative Oncology Group; PS, performance status.
†HR < 1 favors dacomitinib
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

6. ARCHER 1050: Secondary Endpoints
Outcome
Dacomitinib
(n = 227)
Gefitinib
(n = 225)
HR (95% CI)
P Value
Median PFS by investigator assessment, mos (95% CI)
16.6 ( )
11.0 ( )
0.62 ( )
< .0001
ORR, % (95% CI)
74.9 ( )
71.6 ( ) --
.3883
Median DoR, mos (95% CI)
14.8 ( )
8.3 ( )
Median TTF, mos (95% CI)
11.1 ( )
9.2 ( )
0.67 ( )
< .001
OS data not yet mature (36.9% of events at data cutoff)
Pt-reported symptomatic outcomes similar between arms with following statistically significant differences:
Dacomitinib: greater reduction in chest pain, increased diarrhea and sore mouth
Gefitinib: greater improvement in global QoL
DoR, duration of response; QoL, quality of life; TTF, time to treatment failure.
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

7. ARCHER 1050: Adverse Events
AE Occurring in ≥ 15% in Either Arm, %
Dacomitinib (n = 227)
Gefitinib (n = 224)
Any
Gr 1
Gr 2
Gr 3
Diarrhea*
87.2
49.8
28.6
8.4
55.8
46.0
8.9
0.9
Paronychia
61.7
20.3
33.9
7.5
20.1
13.4
5.4
1.3
Dermatitis acneiform
48.9
16.3
18.9
13.7
19.2
9.4
Stomatitis
43.6
22.5
17.6
3.5
17.9
14.7
2.7
0.4
Decreased appetite
30.8
10.1
3.1
24.6
21.4
Dry skin
27.8
18.5
7.9
17.0
15.6
Weight decrease
25.6
9.7
2.2
16.5
9.8
6.3
Alopecia
23.3
18.1
4.8
12.5
11.6
Cough
21.1
17.2
4.0
18.8
16.1
Pruritis
19.8
11.9
13.8
10.7
1.8
ALT increase
19.4
39.3
8.5
AE, adverse event; ALT, alanine aminotransferase; Gr, grade.
*Gr 5 diarrhea, n = 1. Otherwise, no listed AE with severity above grade 3 in either arm.
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

8. ARCHER 1050: Serious AE and Dose Modification
Outcome
Dacomitinib
(n = 227)
Gefitinib
(n = 224)
Serious AE, n (%)
Any
Treatment related
Causing discontinuation
Causing death
62 (27.3)
21 (9.3)
22 (9.7)
2 (0.9)*
50 (22.3)
10 (4.5)
15 (6.7)
1 (0.4)†
Median time to dose reduction, mos (range)
2.8 ( )
3.3 ( )
Median duration of dose reduction, mos (range)
11.3 ( )
5.2 ( )
Reduced dose given, n (%)
30 mg/day
15 mg/day
87 (38.3)
63 (27.8) NA
Pts requiring dose reduction, n (%)
150 (66.1)
18 (8.0)
AE, adverse event; NA, not applicable.
*Untreated diarrhea, untreated cholelithases/liver disease, n =1 each.
†Sigmoid colon diverticulitis/rupture complicated by pneumonia.
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

9. ARCHER 1050: Conclusions
In pts with advanced EGFR-mutant NSCLC, first-line dacomitinib significantly extended median PFS (either by independent review or investigator assessment), DoR, and TTF vs gefitinib
Similar ORR between arms, OS data immature
Dacomitinib toxicity profile consistent with previous reports
Dose modifications more common than with gefitinib
Higher incidence of diarrhea, skin rash, and mucositis than gefitinib
Study investigators conclude that dacomitinib represents new option for treatment-naive pts with advanced EGFR-mutant NSCLC
DoR, duration of response; NSCLC, non-small-cell lung cancer; TTF, time to treatment failure.
Slide credit: clinicaloptions.com
Mok T, et al. ASCO Abstract LBA9007.

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