1. KEYNOTE-024: Extended Survival Outcomes With First-line Pembrolizumab in PD-L1+ NSCLC
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
NSCLC, non-small-cell lung cancer.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. KEYNOTE-024: Background Pembrolizumab approvals for advanced NSCLC
Monotherapy for treatment-naive and previously treated, PD-L1–positive disease
Combination with pemetrexed + carboplatin for treatment-naive, nonsquamous NSCLC[1,2]
KEYNOTE-024: first-line pembrolizumab significantly prolonged PFS and OS, improved ORR, with fewer treatment-related AEs vs platinum-based chemotherapy in PD-L1–positive (≥ 50%) advanced NSCLC[1]
Current analysis updated OS and evaluated PFS2 (time from randomization to progression on second-line therapy or death)[3]
PFS2 recommended to examine effect of crossover on OS and effect of first-line treatment on efficacy of subsequent regimen[4,5]
AE, adverse event; NSCLC, non-small-cell lung cancer.
1. Reck M, et al. N Engl J Med. 2016;375: Pembrolizumab [package insert]
3. Brahmer JR, et al. ASCO Abstract EMA. Evaluation of anticancer medicinal products in man. November Dimopoulos MA, et al. Haematologica. 2015;100:e328-e330.
Slide credit: clinicaloptions.com

3. KEYNOTE-024: Study Design
Randomized, open-label phase III trial
Stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), enrollment region
Pts with untreated stage IV NSCLC, PD-L1 TPS ≥ 50%, ECOG PS 0/1, no activating EGFR mutation/ALK translocation, no active autoimmune disease needing systemic treatment, no untreated brain metastases
(N = 305)
Pembrolizumab 200 mg IV Q3W for up to 2 yrs
(n = 154)
Until PD or unacceptable toxicity
Until PD; crossover allowed to pembrolizumab for up to 2 yrs after BICR-confirmed PD and safety criteria met
Platinum-Doublet CT* for 4-6 cycles
(n = 151)
*Investigator’s choice of: pem + carb; pem + cis; pac + carb; gem + carb; gem + cis. Pem-containing regimens only for nonsquamous histology; these pts could receive pem maintenance treatment.
BICR, blinded independent central review; carb, carboplatin; cis, cisplatin; CT, chemotherapy; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; f/u, follow-up; gem, gemcitabine; NSCLC, non-small-cell lung cancer; pac, paclitaxel; PD, progressive disease; pem, pemetrexed; PFS, progression-free survival; PFS2, PFS with ≥ 1 subsequent line following study treatment; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumor; TPS, tumor proportion score.
Primary analysis endpoints (median f/u: 11.2 mos)
Primary: PFS per RECIST v1.1 (BICR)
Secondary: OS, ORR, safety
Exploratory: DoR, PFS2
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract Reck M, et al. N Engl J Med. 2016;375:

4. KEYNOTE-024: Baseline Characteristics
Pembrolizumab
(n = 154)
Chemotherapy
(n = 151)
Median age, yrs (range)
64.5 ( )
66.0 ( )
Male, n (%)
92 (59.7)
95 (62.9)
ECOG PS 1, n (%)
99 (64.3)
98 (64.9)
Squamous histology, n (%)
29 (18.8)
27 (17.9)
Current/former smoker, n (%)
149 (96.8)
132 (87.4)
Metastases, n (%)
Brain
Liver
18 (11.7)
20 (13.0)
10 (6.6)
36 (23.8)
Prior treatment, n (%)
Neoadjuvant
Adjuvant
Radiation
3 (1.9)
6 (3.9)
35 (22.7)
1 (0.7)
3 (2.0)
43 (28.5)
ECOG, Eastern Cooperative Oncology Group; PS, performance status.
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract 9000.

5. KEYNOTE-024: Pt Disposition With Extended Follow-up
Median follow-up: 19.1 mos (range: mos)
Characteristic
Pembrolizumab
(n = 154)
Chemotherapy
(n = 151)
Treatment status, n
Ongoing
Completed
Discontinued
Received pemetrexed maintenance 46 1
107
N/A 29
120
Median first-line treatment duration, mos (range)
7.9 (1 day to mos)
3.5 (1 day to 22.9 mos)
Effective crossover rate (ITT), %
Crossed over to pembrolizumab, n
Treated with anti–PD-1 outside of crossover, n
60.3 79 12
Any subsequent treatment, n
Of ITT population, %
Of discontinuations, % 48
31.2
44.9 97
64.2
80.8
Median second-line tx duration (range), mos
3.6 (1 day to mos)
3.5 (1 day to mos)
ITT, intent to treat; mos, months; N/A, not applicable.
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract 9000.

6. KEYNOTE-024: Second-line Systemic Tx Use
Subsequent Tx, n (%)
Pembrolizumab Arm
(n = 48)
Platinum doublet
Carb + pem ± bevacizumab*
Carb + pac ± bevacizumab†
Carb + gem
Cis + pem
Cis + gem
Plat + pem
42 (87.5)
17 (35.4)
9 (18.8)
8 (16.7)
5 (10.4)
2 (4.2)
1 (2.1)
Platinum doublet median tx duration, mos (range)
3.6 (1 d to mos)
Other
Cis
Cabozantinib
Carb
Cytarabine
Pem + bevacizumab
6 (12.5)
Nonplatinum doublet median tx duration, mos (range)
2.8 (1 d to mos)
Subsequent Tx, n (%)
Chemotherapy Arm
(n = 97)
Crossover to pembrolizumab
Median tx duration, mos (range)
79 (81.4)
4.2 (1 day to mos)
Anti–PD-1 outside of crossover
Nivolumab
Pembrolizumab
12 (12.4)
9 (9.3)
3 (3.1)
Anti–PD-1 outside of crossover median tx duration, mos (range)
3.0 (1 day to mos)
Other
Pem
Carb + gem
Carb + pac
Doc
Pac
6 (6.2)
2 (2.1)
1 (1.0)
Other median tx duration, mos (range)
1.9 (1 day to 5.2 mos)
carb, carboplatin; cis, cisplatin; doc, docetaxel; gem, gemcitabine; pac, paclitaxel; pem, pemetrexed; plat, platinum; tx, treatment.
*1 pt received bevacizumab. †3 pts received bevacizumab.
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract 9000.

7. KEYNOTE-024: PFS2
Pembrolizumab
(n = 154)
Chemotherapy
(n = 151)
Median PFS2 (95% CI), mos
18.3 (12.7-NE)
8.4 ( )
HR (95% CI)
0.54 ( ); P < .001
Mos
Pts at Risk, n
100 90 80 70 60 50 40 30 20 10
PFS2 (%) 6 3 9 12 18 15 21 24
112 99
96 64
90 56
71 36
40 18
16 6
3 1
59.7% 38.5%
51.0% 24.6%
NE, not estimable; NR, not reached; PFS2, PFS with ≥ 1 subsequent line following study treatment.
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract Reproduced with permission.

8. KEYNOTE-024: OS
Pembrolizumab
(n = 154)
Chemotherapy
(n = 151)
Median OS (95% CI), mos
NR (19.4-NE)
14.5 ( )
HR (95% CI)
0.63 ( ); P = .003
100 90
70.3% 54.8% 80
61.0% 43.0% 70 60
OS (%) 50 40 30 20
NE, not estimable; NR, not reached. 10 3 6 9 12 15 18 21 24
Pts at Risk, n
Mos
112 88
106 79
88 64
57 35
20 15
4 4
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract Reproduced with permission.

9. KEYNOTE-024: Conclusions
With longer follow-up, first-line pembrolizumab demonstrated continued OS benefit vs platinum-based chemotherapy in pts with PD-L1–positive advanced NSCLC
Median OS: NR vs 14.5 mos (HR: 0.63; P = .003)
OS curves remained separated even with effective crossover rate of 60%
PFS2 significantly prolonged for pts allocated to first-line pembrolizumab vs chemotherapy
Median PFS2: 18.3 vs 8.4 mos (HR: 0.54; P < .001)
Investigators concluded that first-line pembrolizumab should be standard of care for NSCLC pts with tumors having PD-L1 TPS ≥ 50% due to prolonged survival and improved safety profile vs platinum-doublet chemotherapy
NR, not reached; NSCLC, non-small-cell lung cancer; PFS2, PFS with ≥ 1 subsequent line following study treatment; TPS, tumor proportion score.
Slide credit: clinicaloptions.com
Brahmer JR, et al. ASCO Abstract 9000.

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