1. KEYNOTE-028: Pembrolizumab in PD-L1+, ER+/HER2- Breast Cancer
CCO Independent Conference Coverage*: The 2015 Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium, December 8-12, 2015
San Antonio, Texas
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from Genentech and Novartis.

2. KEYNOTE-028: Background
Pembrolizumab: anti–PD-1 antibody approved for use in metastatic melanoma and NSCLC but with demonstrated antitumor activity in multiple tumor types
Has single-agent activity in PD-L1+ TNBC[1]
ER+/HER2- most common subtype of breast cancer (> 50%)
4% to 20% ER+/HER2- tumors are also PD-L1+[2-5]
KEYNOTE-028: phase Ib multicohort study of pembrolizumab in pts with PD-L1+ advanced solid tumors
Current report: preliminary efficacy and safety analysis of ER+/HER2- breast cancer cohort in KEYNOTE-028[6]
ER, estrogen receptor; NSCLC, non-small-cell lung cancer; TNBC, triple-negative breast cancer.
1. Nanda R, et al. SABCS Abstract S Ghebeh H, et al. Neoplasia. 2006;8: Muenst S, et al. Br Cancer Res Treatment. 2014;146: Basu G, et al. Cancer Res. 2013;75. Abstract P Sabatier R, et al. Oncotarget ;6: Rugo HS, et al. SABCS Abstract S5-07.
Slide credit: clinicaloptions.com

3. KEYNOTE-028 Breast Cancer Cohort: Study Design
Phase Ib multicohort study
Primary endpoint: ORR
Secondary endpoints: PFS, OS, DoR
Pts with locally advanced or metastatic PD-L1+, ER+/HER2- breast cancer;
failed or ineligible for standard therapy;
ECOG PS 0-1; ≥ 1 measurable lesion;
(N = 25)
Pembrolizumab
10 mg/kg IV Q2W
CR, PR, or SD
Tx to 24 mos or PD or toxicity
PD or unacceptable toxicity
Discontinue
DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; PD, disease progression; SD, stable disease; Tx, treatment.
Rugo HS, et al. SABCS Abstract S5-07.

4. KEYNOTE-028 Breast Cancer Cohort: Baseline Characteristics
Pembrolizumab
(N = 25)
Median age, yrs (range)
53 (36-79)
ECOG PS, %
0/1
Unknown
52/44 4
Elevated lactate dehydrogenase, % 40
Earlier (neo)adjuvant chemotherapy, % 68
Number of lines of earlier therapy for metastatic disease, %
≤ 2 3
≥ 5 20 16 44
Type of earlier therapy, %
Chemotherapy
Hormonal therapy
Other investigational therapy
100 88 24
ECOG PS, Eastern Cooperative Oncology Group performance status.
Slide credit: clinicaloptions.com
Rugo HS, et al. SABCS Abstract S5-07.

5. KEYNOTE-028 Breast Cancer Cohort: Antitumor Activity
Characteristic, % (95% CI)
Pembrolizumab
(N = 25)
ORR
12 ( ) CR
0 (0-13.7)
PR* SD
16 ( )
Clinical benefit rate (CR + PR + SD for ≥ 24 wks)
20 ( ) PD
60 ( )
No assessment†
In 22 pts with ≥ 1 scan after BL
ORR: 14%
CBR: 23%
BL, baseline; CBR, clinical benefit rate; PD, progressive disease; SD, stable disease.
*All had received ≥ 3 lines of prior therapy in metastatic setting.
†Includes pts who discontinued therapy before first post-BL scan.
Slide credit: clinicaloptions.com
Rugo HS, et al. SABCS Abstract S5-07.

6. KEYNOTE-028 Breast Cancer Cohort: Treatment-Related AEs
Median follow-up: 7.3 mos (range: )
No treatment-related deaths
Grade 3/4 AE, %
Pembrolizumab
(N = 25)
Grade 3 autoimmune hepatitis 4
Grade 3 nausea
Grade 3 muscular weakness
Grade 3 ↑ γ-glutamyltransferase
Grade 4 septic shock
AEs ≥ 5%, %
Pembrolizumab
(N = 25)
Any 60
Nausea 20
Fatigue 12
Arthralgia 8
Decreased appetite
Mucosal inflammation
Pruritus
Rash
Blurred vision
Immune-Related AE, %
Pembrolizumab
(N = 25)
Grade 3 autoimmune hepatitis* 4
Grade 2 hyperthyroidism†
Grade 2 hypothyroidism† 12
Grade 1 pneumonitis‡
AE, adverse event; tx, treatment.
*Resulted in tx interruption.
†Managed with oral steroids.
‡No tx indicated.
Slide credit: clinicaloptions.com
Rugo HS, et al. SABCS Abstract S5-07.

7. KEYNOTE-028 Breast Cancer Cohort: Conclusions
In pts with heavily pretreated PD-L1+, ER+/HER2- breast cancer
Pembrolizumab was tolerable with manageable toxicity profile
Pembrolizumab showed ORR of 12% and CBR of 20%
ORR 14%, CBR 23% in 22 evaluable pts
Reponses were durable
Authors suggest further investigation of immune therapies in ER+/HER2- breast cancer
CBR, clinical benefit rate.
Rugo HS, et al. SABCS Abstract S5-07.

8. Go Online for More CCO Coverage of SABCS 2015!
Short slideset summaries of all the key data Additional CME-certified analysis with expert faculty commentary on all the key studies
clinicaloptions.com/oncology