1. KEYNOTE-006: Long-term Outcomes After Pembrolizumab for Advanced Melanoma
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 from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. Long-term Melanoma Outcomes After Pembrolizumab (KEYNOTE-006): Background
Pembrolizumab, an anti–PD-1 mAb, is widely approved for treating advanced or metastatic melanoma
KEYNOTE-006: pembrolizumab vs ipilimumab for unresectable stage III or IV melanoma[1]
Pembrolizumab associated with superior PFS and OS, improved ORR, lower grade 3-5 toxicity[1]
Current analysis evaluated long-term outcomes of KEYNOTE-006[2]
All pts (median follow-up: 33.9 mos)
Pts who completed protocol-specified 2-yr pembrolizumab treatment
Slide credit: clinicaloptions.com
1. Robert C, et al. N Engl J Med. 2015;372: Robert C, et al. ASCO Abstract 9504.

3. KEYNOTE-006: Study Design
International, randomized, open-label, active-controlled phase III study
Stratified by ECOG PS (0 vs 1), line of therapy (1st vs 2nd), PD-L1 status (positive vs negative)
Pembrolizumab
10 mg/kg IV Q2W
(n = 279)
Continued for 2 yrs or until PD or unacceptable toxicity
Pts with unresectable stage III-IV melanoma with ECOG PS 0/1,
≤ 1 prior therapy (excluding anti–CTLA-4, PD-1, or PD-L1 tx), known BRAF-mutation status
(N = 834)
Pembrolizumab
10 mg/kg IV Q3W
(n = 277)
Ipilimumab
3 mg/kg IV Q3W x 4 doses
(n = 278)
DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; PD, progressive disease; PS, performance status; tx, treatment.
Endpoints: primary: PFS, OS; secondary: ORR, DoR, safety
Long-term analysis: pembrolizumab arms pooled for analyses; protocol-specified time on pembrolizumab: ≥ 21.6 mos
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

4. KEYNOTE-006: Baseline Characteristics
Pembrolizumab
(n = 556)
Ipilimumab
(n = 278)
Median age, yrs (range)
62 (18-89)
62 (18-88)
Male, % 60 58
ECOG PS 0, % 69 68
Elevated LDH, % 32 33
BRAF V600–mutation positive, % 35 38
PD-L1 positive, % 80 81
M1c disease, % 66 64
1 prior therapy, % 34
ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status.
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

5. KEYNOTE-006: Post-Study Therapy
Pembrolizumab
(n = 555)
Ipilimumab
(n = 256)
Any antineoplastic therapy 44 54
Immunotherapy
Anti–CTLA-4
Anti–PD-1
Anti–PD-L1
Anti–CTLA-4 + anti–PD-1 31 25 9*
< 1 39 5
34†
BRAF inhibitor ± MEK inhibitor 23 32
Chemotherapy 11 12
Other 4
*Pembrolizumab, n = 27; nivolumab, n = 22. †Pembrolizumab, n = 44; nivolumab, n = 42.
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

6. KEYNOTE-006: Long-term Outcomes
Pembrolizumab
(n = 556)
Ipilimumab
(n = 278) HR
(95% CI)
Median PFS, mos (95% CI)
24 mos, %
33 mos, %
8.3 ( ) 34 31
3.3 ( ) 15 14
0.56 ( )
Median OS, mos (95% CI)
32.3 (24.5-NR) 55 50
15.9 ( ) 42 39
0.70 ( )
ORR, % (95% CI) CR PR SD PD
42 (38-46)
13 (11-16)
29 (25-33)
21 (18-25)
29 (26-33)
16 (12-21)
3 (1-6)
14 (10-18)
25 (20-31)
39 (33-45)
Median DoR, mos (range)
NR (1.0+ to 33.8+)
NR (1.1+ to 34.8+)
DoR, duration of response; NR, not reached; PD, progressive disease; SD, stable disease.
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

7. KEYNOTE-006: Outcomes After Completing Pembrolizumab
19% of pts receiving pembrolizumab completed protocol (n = 104)
98% (n = 102) alive after median follow-up 9.7 mos; 93% (n = 97) with ongoing responses
Outcome
Pts Who Completed Pembrolizumab
(n = 104)
Best overall response, % CR PR SD 23 65 12
Estimated PFS, % (95% CI)
91 (80-96)*
Estimated PFS by best response, % (95% CI)
95 (69-99)
91 (74-97)
83 (48-96)
SD, stable disease.
*Median PFS: not reached.
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

8. KEYNOTE-006: Exposure and Adverse EventsAE
Pembrolizumab
(n = 555)
Ipilimumab
(n = 256)
Median exposure, mos (range)
5.70 ( )
2.10 ( )
Treatment-related AE, %
Grade 3/4
Led to death
Led to discontinuation 79 17
< 1 10 74 19 9
Immune-mediated AE, % 26 5 12
AE, adverse event.
Most common immune-mediated AEs (all incidence ≤ 11%): hypothyroidism, hyperthyroidism, colitis, skin disorders, pneumonitis
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

9. KEYNOTE-006: Conclusions
Superiority of pembrolizumab over ipilimumab confirmed in advanced melanoma with nearly 3-yr median follow-up
Prolonged PFS, OS with pembrolizumab
Favorable safety profile with pembrolizumab
Favorable outcomes for pts who completed protocol-specified pembrolizumab treatment
91% PFS after median follow-up 9.7 mos
Investigators concluded that data from this study further support pembrolizumab as standard of care for advanced melanoma
Slide credit: clinicaloptions.com
Robert C, et al. ASCO Abstract 9504.

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