1. PHEREXA: Survival Data
Capecitabine (X) +
trastuzumab (H)
Eligibility
HER2+ mBC
Prior treatment with taxane
Progression on 1st-line trastuzumab-based therapy R
X + H + pertuzumab (P)
H + X (n = 224 )
H + X + P (n = 228)
Hazard ratio
p-value
Median PFS by IRF
9.0 mo
11.1 mo
0.82
0.07
Median OS (mo)
28.1
36.1
0.68 NE
IRF = independent review facility; NE = not evaluable due to hierarchial testing of OS after the primary IRF PFS endpoint
Urruticoechea A et al. Proc ASCO 2016;Abstract 504.

2. “In patients who have not been treated with pertuzumab and chemotherapy, it is reasonable to offer this treatment in the second-line setting.”
Hope S Rugo, MD

3. HERITAGE: A Phase III Trial of Proposed Trastuzumab Biosimilar Myl-1401O in HER2+ mBC
Myl-1401O + taxane
(n = 230)
Trastuzumab + taxane
(n = 228)
ORR at 24 weeks
69.6%
64.0%
95% CI
(63.62, 75.51)
(57.81, 70.26)
Ratio of ORR: Myl-1401O/ trastuzumab (FDA)
1.09
Difference in ORR:
Myl-1401O/trastuzumab (EMEA)
5.53
Results confirmed efficacy equivalence based on ratio of ORR and difference in ORR.
No difference in median LVEF between the 2 study arms
Similar immunogenicity was observed
Rugo HS et al. Proc ASCO 2016;Abstract LBA503.

4. Use of Trastuzumab Biosimilar Myl-1401O in the Adjuvant Setting “I feel that based on this data and all of the similar physical and immunologic characteristics that it would be safe to use [Myl-1401O] as a substitute for trastuzumab.”
Hope S Rugo, MD

5. Trials of Checkpoint Inhibitors in TNBC
Phase IB KEYNOTE-012: Pembrolizumab in TNBC
N = 27 women with PD-L1-positive tumors evaluable for response
ORR = 18.5%
Duration of response: Not yet reached
Phase Ia study of atezolizumab in TNBC
N = 21 women with PD-L1-positive tumors evaluable for response
ORR = 19%
Nanda R et al. J Clin Oncol 2016;34(21):2460-7; Emens LA et al. Proc AACR 2015;Abstract 6317.

6. Placebo q2wk + nab-paclitaxel
IMpassion130: Phase III Randomized Trial of Atezolizumab with Nab-Paclitaxel for 1st-line Metastatic Triple-Negative Breast Cancer (mTNBC)
Target Accrual: 900 (Active, recruiting)
Eligibility
Locally advanced, measurable TNBC or mTNBC
No prior systemic therapy for advanced TNBC
ECOG PS 0-1
No history of autoimmune disease
Atezolizumab 840 mg q2wk + nab-paclitaxel (100 mg/m2, 3 wks on/1 off) x ≥6 R
Placebo q2wk + nab-paclitaxel
(100 mg/m2, 3 wks on/1 off) x ≥6
Primary Endpoints: PFS, OS
Stratification: Liver metastases; prior taxane; PD-L1 status
September Identifier: NCT
Emens LA et al. Proc ASCO 2016;Abstract TPS1104.

7. “In patients with AR-positive disease who are not eligible for clinical trials, it is reasonable to obtain enzalutamide or bicalutamide on compassionate use if the patient does not need an immediate response.”
Hope S Rugo, MD

8. Ongoing Phase III Trials of PARP Inhibitors in TNBC or BRCA Mutation-Positive Breast Cancer
Trial name N
Eligibility
Randomization
OlympiAD
310
gBRCA+ mBC
Olaparib
Placebo
OlympiA
1,500
High-risk HER2- primary BC
gBRCA+
Brightness
624
Early-stage TNBC
Veliparib + carboplatin + paclitaxel  AC
Placebo + carboplatin + paclitaxel  AC
Placebo + placebo + paclitaxel  AC
EMBRACA
429
Unresectable metastatic or locally advanced HER2- BC
≤3 chemotherapy regimens for mBC
Talazoparib
Physician’s choice
September 2016.

9. Utility of 21-Gene Recurrence Score and 70-Gene Signature “We do tend to use the 21-gene score a lot about decisions about chemotherapy for node-negative disease. And then we tend to use the 70-gene score a little bit more about decisions in terms of trial participation in the neoadjuvant setting and in differentiating difficult situations where patients have a lot of bulk of disease.”
Hope S Rugo, MD

10. SWISH: Prevention of Everolimus-Associated Stomatitis
Treatment included:
Everolimus 10 mg and exemestane 25 mg QD
10 mL of commercially available 0.5 mg/mL dexamethasone oral solution, swish x 2 min and spit QID for 8 weeks
Stomatitis Grade %
Study
All 1 2 3 4
SWISH at 8 weeks
(N = 92)
19.8
17.4
2.4
BOLERO-2 (total) 67 34 25 8
Rugo HS et al. Proc ASCO 2016;Abstract 525.

11. Steroid Mouthwashes and Everolimus-Associated Stomatitis “I believe that this should now be our standard of care for patients receiving the mTOR inhibitor everolimus, because we can tremendously improve the rate of stomatitis and, therefore, quality of life.”
Hope S Rugo, MD

12. Potential Management Approaches for mTOR Inhibitor-Associated Fatigue and Pneumonitis
Methylphenidate
Dose reductions/treatment holiday
Rule out other etiology — hypothyroidism, polypharmacy
Interstitial pneumonitis
If only radiographic evidence, no further intervention
If Grade 2, stop drug and administer steroids as needed
Resume drug once patient is recovered

13. Practical Considerations for Use of Cooling Cap Systems
Facility/Personnel
Availability of freezer space (does not apply to DigniCap)
Personnel time/postcooling time

14. Practical Considerations for Use of Cooling Cap Systems
Facility/Personnel
Availability of freezer space (does not apply to DigniCap)
Personnel time/postcooling time
Patient
Cost
Discomfort
Time
Restrictions on shampooing/styling of hair

15. Phase II/III Trial of OPT-822/OPT-821 Vaccine Therapy in Patients with mBC
OPT-822: Globo-H/keyhole limpet hemocycanin (KLH) conjugate
Globo H is glycolipid highly expressed in BC
OPT-821: Adjuvant for vaccine
N = 349 patients randomized 2:1 to subcutaneous OPT-822/OPT-821 or control until PD (with low-dose cyclophosphamide)
No difference was observed in PFS (p = 0.77) or in interim OS (p = 0.29)
PFS and OS were significantly improved in the 50% of patients who developed a Globo H-specific IgG response to OPT-822/OPT-821 any time during treatment
OPT-822/OPT-821 was well tolerated with the most common drug-related adverse event being Grade 1/2 injection reaction.
Huang C-S et al. Proc ASCO 2016;Abstract 1003.

16. Palbociclib + fulvestrant
Efficacy of Palbociclib and Fulvestrant in Patients with mBC and ESR1 Mutations
N = 395 patients with successful ESR1 mutation analysis from PALOMA-3 trial
ESR1 mutations were strongly associated with acquired resistance to prior aromatase inhibitors
Median PFS (months)
Palbociclib + fulvestrant
Placebo + fulvestrant
HR (p-value)
ESR1-positive (n = 67; 39)
9.4
4.1
0.524 (0.0052)
ESR1-negative (n = 198; 91)
9.5
3.8
0.438 (<0.0001)
Palbociclib offers high efficacy regardless of ESR1 mutation status
Turner NC et al. Proc ASCO 2016;Abstract 512.

17. Clinical Data with CDK4/6 Inhibitors Ribociclib and Abemaciclib in ER-Positive mBC
MONALEESA-2: A Phase III trial of first-line ribociclib + letrozole versus letrozole alone
Clinically significant improvement in PFS with ribociclib + letrozole
MONARCH1: A Phase II trial of abemaciclib after endocrine therapy and chemotherapy
In N = 132 patients, ORR = 19.7%
Phase II trial of abemaciclib in patients with brain metastases secondary to HR-positive mBC, NSCLC or melanoma
Exploratory analysis of n = 3 patients with mBC treated with abemaciclib detected abemaciclib and its active metabolites in resected brain metastases
Press release, May 18, Novartis; Dickler MN et al. Proc ASCO 2016;Abstract 510; Sahebjam S et al Proc ASCO 2016;Abstract 526.

18. ExteNet: DFS at 2-Year Follow-Up (Intent to Treat)
Neratinib (n = 1,420)
Placebo (n = 1,420)
Hazard ratio
p-value
DFS including DCIS
93.9%
91.0%
0.63
0.0017
Invasive DFS (IDFS)
91.6%
0.67
0.0091
HR-positive
95.4%
91.2%
0.51
0.0013
HR-negative
92.0%
92.2%
0.93
0.74
Neratinib for 12 months post-trastuzumab significantly improved 2-yr IDFS
Grade 3/4 diarrhea was the most common adverse event leading to dose reductions/discontinuation of neratinib in 26%/17% of patients
Chan A et al. Lancet Oncol 2016;17(3):

19. KEYNOTE-012: Possible Immune-Mediated Adverse Events
One case each:
Grade 3 colitis
Grade 3 hepatitis
Grade 2 hypothyroidism
Case of colitis reported 40 days after last pembrolizumab dose and after patient started subsequent therapy with capecitabine
One case of Grade 2 enterocolitis accompanied by Grade 3 diarrhea reported 136 days after last pembrolizumab dose and 94 days after the start of eribulin.
Nanda R et al. J Clin Oncol 2016;34(21):

20. CREATE-X: A Phase III Trial of Adjuvant Capecitabine in HER2-Negative BC with Pathologic Residual Invasive Disease After Neoadjuvant Chemotherapy
Capecitabine
Control
HR (p-value)
2-year DFS rate
87.3%
80.5%
0.688 (0.001)
2-year OS rate
96.2%
93.9%
0.658 (0.086)
Lee S-J et al. San Antonio Breast Cancer Symposium 2015;Abstract S107.

21. MA.17R: A Phase III Trial of Extended Adjuvant Letrozole
Placebo
HR (p-value)
5-year DFS rate
95%
91%
0.66 (0.01)
5-year OS rate
93%
94%
0.97 (0.83)
Annual incidence rate —contralateral BC
0.21%
0.49%
0.42 (0.007)
Bone-related toxic events occurred more frequently with letrozole
Bone pain
Bone fractures
New-onset osteoporosis
Goss PE et al. N Engl J Med 2016:375(3):

22. PALOMA-2: A Phase III Trial of First-Line Palbociclib with Letrozole
Palbociclib + letrozole
(n = 444)
Placebo + letrozole
(n = 222)
HR (p-value)
Median PFS
24.8 mo
14.5 mo
0.58 (< )
Hematologic AEs, %
Palbociclib + letrozole
(n = 444)
Placebo + letrozole
(n = 222)
Any grade
Grade 3
Grade 4
Neutropenia 80 56 10 6 1
<1
Leukopenia 39 24 2
Anemia 5 9
Thrombocytopenia 16
Finn RS et al. Proc ASCO 2016;Abstract 507.

23. MONARCH-1: A Phase II Study of Single-Agent Abemaciclib in HR+/HER2-Negative mBC After Chemotherapy
In N = 132 heavily pretreated patients, abemaciclib demonstrated single-agent activity:
ORR = 19.7%
Median PFS = 6.0 mo
Median OS = 17.7 mo
Select most common AEs
All grade
Grade 3
Grade 4
Creatinine increased
98.5%
0.8%
Diarrhea
90.2%
19.7%
Neutrophil decreased
87.7%
22.3%
4.6%
Platelet count decreased
41.4%
2.3%
Dickler MN et al. Proc ASCO 2016;Abstract 510.

24. Abemaciclib + anastrozole
neoMONARCH: A Phase II Neoadjuvant Trial of Abemaciclib or Anastrozole Alone or the Combination
Trial Identifier: NCT Enrollment: 148 (Closed)
Abemaciclib
Eligibility
Postmenopausal
HR+/HER2-negative breast adenocarcinoma
Clinical Stage I (≥1 cm), Stage II, Stage IIIA or IIIB R
After day 14 all pts receive the combination for 14 weeks
Anastrozole
Abemaciclib + anastrozole
Primary endpoint: Change in Ki-67 levels between baseline and after 2 weeks of therapy
September 2016.

25. monarcHER: A Phase II Randomized Trial of Abemaciclib in Locally Advanced or Metastatic BC
Trial Identifier: NCT Enrollment: 225 (Open)
Eligibility
Postmenopausal
HR+/HER2-positive breast adenocarcinoma
Must have received:
Taxane
T-DM1
At least 2 anti-HER2 agents for advanced disease
Abemaciclib + trastuzumab + fulvestrant R
Abemaciclib + trastuzumab
Trastuzumab + standard chemotherapy
Primary endpoint: Progression-free survival
September 2016.

26. ASCO Practice Guideline: Use of Biomarkers to Guide Adjuvant Systemic Therapy Decisions
For a patient with ER/PR-positive/HER2-negative, node-positive breast cancer, the clinician should not use certain biomarkers to guide adjuvant treatment decisions, including those below:
Oncotype DX
EndoPredict
MammaPrint
PAM50
Breast Cancer Index
Mammostrat
Immunohistochemistry 4
Harris LN et al. J Clin Oncol 2016;34(10):

27. 6 cycles of neoadjuvant therapy
KRISTINE: A Phase III Trial of Neoadjuvant HER2 Targeted Therapy with or without Chemotherapy
Docetaxel S U R G E Y
Carboplatin
Trastuzumab
TCH+P
Centrally confirmed HER2- positive, operable, locally advanced or inflammatory breast cancer
Tumor >2cm
Trastuzumab
Pertuzumab
Pertuzumab R
6 cycles of neoadjuvant therapy
12 cycles of adjuvant
HER2-therapy
T-DM1
T-DM1
T-DM1+P
Pertuzumab
Pertuzumab
pCR in breast and lymph nodes: THCP = 56%, T-DM1 + P = 44%
Hurvitz SA et al. Proc ASCO 2016;Abstract 500.

28. BCIRG-006: 10-Year Follow-Up
DFS (≥4 positive nodes): TCH = 62.9%, AC-TH = 62.8%, AC-T = 53.6%
Therapeutic Index:
AC  TH
TCH
DFS events (n = 1,074; 1,075)
269
279
Grade 3/4 CHF (n = 1,068; 1,056) 21 4
Totals
290
283
Rx-related leukemias (n = 1,068; 1,056)
7(8)*
0(1)†
Sustained LVEF loss >10% (n = 1,042; 1,031)
200 97
* Only in AC-Rx patients; † Leukemia developed after CHOP Rx
Slamon DJ et al. Proc SABCS 2015;Abstract S5-04.