1. APHINITY: Adjuvant Pertuzumab + Trastuzumab and Chemotherapy for HER2+ EBC
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
EBC, early breast cancer.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. APHINITY: Background
Dual HER2 inhibition with addition of pertuzumab to trastuzumab + docetaxel as first-line therapy significantly extended PFS, OS in pts with HER2+ mBC[1]
Combining pertuzumab with trastuzumab + docetaxel as neoadjuvant therapy also significantly increased pCR in pts with HER2+ EBC[2]
Adjuvant trastuzumab + CT for a yr current SoC for HER2+ EBC
However, some pts with HER2+ EBC will still have recurrent disease[3]
APHINITY assessed efficacy, safety of adjuvant pertuzumab combined with trastuzumab + CT in pts with treatment/radiotherapy-naive HER2+ EBC[4]
BC, breast cancer; CT, chemotherapy; EBC, early breast cancer; mBC, metastatic breast cancer; pCR, pathological CR; SoC, standard of care; tx, treatment.
1. Swain SM, et al. N Engl J Med. 2015;372: Gianni L, et al. Lancet Oncol. 2012;13: Cameron D, et al. Lancet. 2017;389: von Minckwitz G, et al. ASCO Abstract LBA500.
Slide credit: clinicaloptions.com

3. APHINITY: Study Design
International, randomized, double-blind, placebo-controlled phase III trial[1,2]
Primary endpoint: IDFS per modified STEEP definition[3] (excludes second primary non-BC as event)
Secondary endpoints: IDFS per STEEP definition,[3] OS, distant recurrence-free survival, DFS, recurrence-free interval, safety, cardiac safety, health-related QoL
Stratified by CT, nodal status, HR status, geographic region, protocol version (A vs B)
Wk 52
Pts with HER2+ EBC, no prior invasive BC or anticancer tx or radiotherapy, node positive + any tumor size (no T0) or node negative + tumor size > 1 cm,* BL LVEF ≥ 55%
(N = 4805)
Pertuzumab + Trastuzumab + CT†
(n = 2400)
Surgery
10-yr follow-up
Placebo + Trastuzumab + CT†
(n = 2405)
*Or node negative + 1 of following: for tumors > 0.5, ≤ 1 cm, at least 1 histologic/nuclear grade 3; ER negative and PgR negative; aged < 35 yrs. †Tx initiated ≤ 8 wks post surgery. Permitted CT: standard anthracycline or nonanthracycline regimens. Endocrine and/or radiotherapy could be started at end of adjuvant CT.
BC, breast cancer; BL, baseline; CT, chemotherapy; DFS, disease-free survival; EBC, early breast cancer; HR, hormone receptor; IDFS, invasive disease-free survival; LVEF, left ventricular ejection fraction; QoL, quality of life; tx, treatment.
1. von Minckwitz G, et al. ASCO Abstract LBA ClinicalTrials.gov. NCT Hudis CA, et al. J Clin Oncol. 2007;25:
Slide credit: clinicaloptions.com

4. APHINITY: Pt Characteristics in ITT Population
Characteristic, n (%)
Pertuzumab
(n = 2400)
Placebo
(n = 2404)
Nodal status
0 positive nodes + T ≤ 1 cm
0 positive nodes + T > 1 cm
1-3 positive nodes
≥ 4 positive nodes
90 (3.8)
807 (33.6)
907 (37.8)
596 (24.8)
84 (3.5)
818 (34.0)
900 (37.4)
602 (25.0)
Adjuvant CT regimen (randomized)
Anthracycline containing
Nonanthracycline containing
1865 (77.7)
535 (22.3)
1877 (78.1)
527 (21.9)
HR status (central determination)
Negative (ER- and PgR-)
Positive (ER+ and/or PgR+)
864 (36.0)
1536 (64.0)
858 (35.7)
1546 (64.3)
Protocol version A
Amendment B*
1828 (76.2)
572 (23.8)
1827 (76.0)
577 (24.0)
CT, chemotherapy; HR, hormone receptor; ITT, intent to treat.
*Capped node-negative enrollment in November 2012 (recruitment started November 2011); added 1000 node-positive pts and increased sample size to 4800 pts total.
Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO Abstract LBA500.

5. APHINITY: Interim Analysis of IDFS
Data cutoff in December 2016 after IDFS events (median f/u: 45.4 mos)
Most first events were visceral, distant
98.6%
96.4%
94.1%
92.3%
100
98.8%
95.7%
93.2%
90.6% 80
(Expected: 89.2%)
IDFS Event, n (%)
Pertuzumab (n = 2400)
Placebo (n = 2404)
All pts with IDFS event
171 (7.1)
210 (8.7)
First event type
Distant recurrence
Locoregional recurrence
Contralateral BC
Death
112 (4.7)
26 (1.1)
5 (0.2)
28 (1.2)
139 (5.8)
34 (1.4)
11 (0.5)
All pts with distant recurrence
119 (5.0)
145 (6.0)
First distant recurrence site
Lung/liver/pleural effusion
CNS
Other
Bone
43 (1.8)
46 (1.9)
9 (0.4)
21 (0.9)
61 (2.5)
45 (1.9)
30 (1.2) 60
IDFS (%) 40
Pertuzumab
Placebo
Stratified HR: (95% CI: ; P = .045) 20
BC, breast cancer; CNS, central nervous system; f/u, follow-up; IDFS, invasive disease-free survival; ITT, intent to treat. 6 12 18 24 30 36 42 48
Mos
Pts at Risk, n
Pertuzumab
Placebo
ITT population.
Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO Abstract LBA500. Reproduced with permission.

6. APHINITY: Secondary Endpoints
3-Yr Endpoint, %
Pertuzumab
(n = 2400)
Placebo
(n = 2404)
HR (95% CI)*
P Value
IDFS (modified STEEP)
Node positive
Node negative
HR positive
HR negative
94.1
92.0
98.4
94.8
92.8
93.2
90.2
97.5
94.4
91.2
0.81 ( )
0.77 ( )
1.13 ( )
0.86 ( )
0.76 ( )
.045
.019
.644
.277
.085
IDFS (STEEP)
93.5
92.5
0.82 ( )
.043
OS†
97.7
0.89 ( )
.467
DRFI
95.7
95.1
0.82 ( )
.101
DRFI, distant recurrence-free interval; HR, hormone receptor; IDFS, invasive disease-free survival; ITT, intent to treat.
ITT population.
*Stratified HR for overall IDFS, unstratified HR for IDFS subgroups.
†OS for first interim analysis at 26% of target events.
Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO Abstract LBA500.

7. Treatment Difference (95% CI)
APHINITY: Safety
Outcome, n (%)
Pertuzumab
(n = 2364)
Placebo (n = 2405)
Treatment Difference (95% CI)
Primary cardiac endpoint
Heart failure NYHA III/IV + LVEF drop*
Cardiac death†
Recovered according to LVEF
17 (0.7)
15 (0.6)
2 (0.08)
7 (0.3)
8 (0.3)
6 (0.2)
4 (0.2)
0.4% (0% to 0.8%)
Asymptomatic or mildly symptomatic LVEF drop‡
64 (2.7)
67 (2.8)
-0.1% (-1.0% to 0.9%)
Grade ≥ 3 AEs
Neutropenia
Febrile neutropenia
Decreased neutrophil count
Diarrhea
Anthracycline CT, n/N (%)
Nonanthracycline CT, n/N (%)
Anemia
385 (16.3)
287 (12.1)
228 (9.6)
232 (9.8)
137/1834 (7.5)
95/528 (18.0)
163 (6.9)
377 (15.7)
266 (11.1)
230 (9.6)
90 (3.7)
59/1894 (3.1)
31/510 (6.1)
113 (4.7)
Fatal AE
18 (0.8)
20 (0.8)
AE, adverse event; BL, baseline; CT, chemotherapy; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association.
*LVEF drop defined as ejection fraction decrease ≥ 10% from BL to below 50%. †Determined by Cardiac Advisory Board per prospective definition. ‡Secondary cardiac endpoint.
Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO Abstract LBA500.

8. APHINITY: Conclusions
Adjuvant pertuzumab + trastuzumab + CT significantly reduced risk of recurrence events vs placebo + trastuzumab + CT in pts with HER2+ EBC
HR: 0.81 (95% CI: ; P = .045)
Pts with node-positive or HR-negative disease had greatest IDFS benefit
Most recurrences to distant sites (pertuzumab: 4.7%; placebo: 5.8%)
Investigators concluded:
No new safety signals identified with addition of pertuzumab to trastuzumab + CT
Low incidence of cardiac events
No difference in fatal AE rates between arms (0.8% for both)
Increased diarrhea incidence with pertuzumab (any-grade: 71.2% vs 45.2% with placebo)
Ongoing follow-up important to determine long-term IDFS, safety, and OS
AE, adverse event; CT, chemotherapy; EBC, early breast cancer; HR, hormone receptor; IDFS, invasive disease-free survival.
Slide credit: clinicaloptions.com
von Minckwitz G, et al. ASCO Abstract LBA500.

9. 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, gastrointestinal, genitourinary, lung, and skin cancers
Gynecologic and hematologic malignancies
clinicaloptions.com/oncology