The study evaluated adding vemurafenib to irinotecan and cetuximab for patients with BRAF V600E metastatic colorectal cancer. It found that progression-free survival was significantly improved with the combination, with a median of 4.3 months compared to 2.0 months for irinotecan and cetuximab alone. Overall survival showed a numerical improvement with the combination but did not reach statistical significance. The combination was associated with more grade 3-4 adverse events but provided a benefit for patients who crossed over to it after progression on irinotecan and cetuximab. The investigators concluded vemurafenib in combination with irinotecan and

1. SWOG S1406: Vemurafenib in Combination
With Irinotecan and Cetuximab in BRAF
V600E Metastatic CRC
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
This activity is supported by educational grants by AbbVie, Amgen, AstraZeneca,
Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co, Inc..

2. SWOG S1406: Background
 BRAF V600E: mutation leading to constitutive activation of BRAF kinase and
MAPK pathway[1]
– BRAF mutated in ~ 8% of mCRC cases
– Associated with aggressive disease, poor prognosis, minimal benefit from
standard chemotherapy[2]
 Vemurafenib: kinase inhibitor selective for mutated BRAF protein[3]
– Vemurafenib monotherapy associated with limited activity in mCRC
– Phase I study suggested improved survival and response in combination with
irinotecan + cetuximab in refractory mCRC with BRAF V600E[4]
 Current study evaluated efficacy and safety of vemurafenib addition to
irinotecan + cetuximab in pts with BRAF V600E mCRC[5]
Slide credit: clinicaloptions.com
References in slidenotes.

3. SWOG S1406: Study Design
 Randomized, multicenter, open-label phase II trial
Slide credit: clinicaloptions.com
Kopetz S, et al. ASCO 2017. Abstract 3505. ClinicalTrials.gov. NCT02164916.
Pts with mCRC, extended RAS WT and
BRAF V600E, previously treated with 1-2
systemic CT lines for metastatic or
advanced unresectable disease, no prior
panitumumab or cetuximab, no prior BRAF
or MEK inhibitors, ECOG PS 0-1
(N = 106)*
Until PD
Until PD; crossover
allowed to
vemurafenib arm
after PD
Cetuximab 500 mg/m2 IV Q2W +
Irinotecan 180 mg/m2 IV Q2W
(n = 50)
Vemurafenib 960 mg PO BID +
Cetuximab 500 mg/m2 IV Q2W +
Irinotecan 180 mg/m2 IV Q2W
(n = 49)
 Primary endpoint: PFS
 Secondary endpoints: OS, ORR, treatment-related AEs
Stratified by prior irinotecan treatment (yes vs no)
Randomized 1:1
*Only 99 pts eligible to receive treatment after randomization.

4. SWOG S1406: Baseline Characteristics
Slide credit: clinicaloptions.com
Kopetz S, et al. ASCO 2017. Abstract 3505.
Characteristic, n (%)
VIC
(n = 49)
IC
(n = 50)
Median age, yrs (range) 60 (34-83) 62 (31-83)
Female 21 (43) 37 (74)
Race
 White
 Black
 Asian
43 (88)
1 (2)
4 (8)
49 (98)
0 (0)
1 (2)
Hispanic ethnicity 2 (4) 2 (4)
ECOG PS 1 25 (51) 27 (54)
Prior irinotecan 20 (41) 19 (38)
Prior regimens for mCRC
 1
 2
 Failed adjuvant within 6 mos
27 (55)
19 (39)
3 (6)
26 (52)
17 (34)
7 (14)

5. SWOG S1406: PFS (Primary Endpoint)
Slide credit: clinicaloptions.com
PFS
(%)
HR: 0.48 (95% CI: 0.31-0.75; P = .001)
Events, n mPFS (95% CI)
VIC 40 4.3 (3.6-5.7)
IC 48 2.0 (1.8-2.1)
Kopetz S, et al. ASCO 2017. Abstract 3505. Reproduced with permission.
 Median follow-up: 7.3 mos
 Among 48% of pts who
crossed over to VIC after PD
on IC, mPFS was 5.8 mos
 PFS significantly prolonged
with vemurafenib in most
subgroups
– Significant benefit in pts
with tumors on right vs
left/rectum, no prior
irinotecan, MSS, or mutated
PIK3CA
0
20
40
60
80
100
0 3 6 8 10 12 14
Mos

6. SWOG S1406: OS, Response
 In crossover pts, mOS: 12.1 mos (95%
CI: 4.5-12.5)
 Distribution of responses significantly
different with addition of vemurafenib vs
IC alone (Chi-squared P = .001)
Slide credit: clinicaloptions.com
Endpoint, %
VIC
(n = 44)*
IC
(n = 47)*
Crossover
(n = 24)†
PR‡ 16 4 17
SD 50 17 55
PD§ 18 66 NR
DCR 67 22 72
*Measurable disease in 93 pts overall. †Excludes 6 pts (2 pts
without PD before crossover, 4 pts without measurable disease).
‡Includes confirmed and unconfirmed. §Includes symptomatic
deterioration.
mOS, Mos 95% CI
VIC 9.6 (7.5-13.1)
IC 5.9 (3.0-9.9)
HR: 0.73 (95% CI: 0.45-1.17; P = .19)
OS
(%)
0
20
40
60
80
100
0 3 6 9 12 15 18
Mos
Kopetz S, et al. ASCO 2017. Abstract 3505. Reproduced with permission.

7. SWOG S1406: Safety
 AE-related discontinuations more
common with vemurafenib
combination (16%) vs cetuximab
+ irinotecan alone (6%)
 Median duration of treatment
imbalanced between arms
– 88 days for VIC
– 47 days for IC
Slide credit: clinicaloptions.com
Kopetz S, et al. ASCO 2017. Abstract 3505.
Grade 3/4 AE, n (%)
VIC
(n = 46)
IC
(n = 46)
Anemia 6 (13) 0 (0)
Dehydration 5 (11) 3 (7)
Diarrhea 11 (24) 6 (13)
Febrile neutropenia 5 (11) 2 (4)
Fatigue 7 (15) 7 (15)
Neutropenia 15 (33) 3 (7)
Rash 2 (4) 3 (7)
Hypomagnesemia 0 (0) 2 (4)
Nausea 9 (20) 1 (2)
Arthralgia 3 (7) 0 (0)

8. SWOG S1406: Investigator Conclusions
 Addition of vemurafenib to cetuximab + irinotecan associated with significantly
prolonged PFS in mCRC pts with BRAF V600E
– mPFS: 4.3 vs 2.0 mos, respectively (HR: 0.48; P = .001)
– PFS benefit observed across most subgroups
 Addition of vemurafenib associated with benefit in pts crossing over after PD on IC
alone
– mPFS: 5.8 mos; mOS: 12.1 mos
 mOS numerically higher with VIC (9.6 mos) vs IC alone (5.9 mos), but did not reach
statistical significance (HR: 0.73; P = .19)
– Analysis limited by 48% crossover to VIC after PD on IC alone
 Investigators concluded that VIC is a new treatment for BRAF V600E mCRC
Slide credit: clinicaloptions.com
Kopetz S, et al. ASCO 2017. Abstract 3505.

9. clinicaloptions.com/oncology
Go Online for More CCO
Coverage of ASCO 2017!
Short slideset summaries and additional CME-certified analyses with expert faculty
commentary on key studies in:
 Breast cancer
 Gastrointestinal cancer
 Genitourinary cancer
 Gynecologic cancers
 Hematologic malignancies
 Lung cancer
 Skin cancer