Fase III que utiliza Nab-Paclitaxel + Carboplatino y Pembrolizumab en NSCLC escamoso. El hazard ratio favorece a Nab paclitaxel en el análisis de subgrupos.

1. KEYNOTE-407: Phase III Trial of Carboplatin +
Paclitaxel/nab-Paclitaxel ± Pembrolizumab in
Patients With Untreated Stage IV Squamous NSCLC
This activity is supported by educational grants from Amgen; Astellas; AstraZeneca;
Celgene Corporation; Eisai; Genentech; Janssen; Merck & Co., Inc.; and Seattle Genetics.
CCO Independent Conference Highlights*
of the 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, Illinois
*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.

2. Carboplatin + Paclitaxel/nab-Paclitaxel ±
Pembrolizumab in NSCLC (KEYNOTE-407): Background
 Pembrolizumab: monoclonal antibody targeting PD-1
‒ Significantly improved OS and PFS with fewer AEs vs platinum-based
chemotherapy in patients with untreated advanced squamous or
nonsquamous PD-L1–positive NSCLC[1]
‒ Significantly improved OS and PFS when added to pemetrexed + a
platinum-based agent in patients with untreated metastatic
nonsquamous NSCLC, regardless of PD-L1 status[2]
 Current prespecified second interim analysis evaluates efficacy and
safety of pembrolizumab addition to platinum-based chemotherapy in
patients with untreated metastatic squamous NSCLC[3]
1. Reck M, et al. N Engl J Med. 2016;375:1823-1833. 2. Gandhi L, et al. N Engl J Med.
2018;378:2078-2092. 3. Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com

3.  Randomized, double-blind phase III trial
 Primary endpoint: PFS by RECIST v1.1 (BICR), OS
 Secondary endpoints: ORR and DoR by RECIST v1.1 (BICR), safety
KEYNOTE-407: Study Design
Paz-Ares LG, et al. ASCO 2018. Abstract 105. ClinicalTrials.gov. NCT02775435. Slide credit: clinicaloptions.com
Pembrolizumab + Carboplatin +
Paclitaxel or nab-Paclitaxel
3-wk cycles x 4
(n = 278)
Patients with untreated stage IV
squamous NSCLC, ECOG PS 0/1,
available tumor biopsy for PD-L1
assessment, no brain mets, and
no pneumonitis requiring
systemic steroids
(N = 559)
Stratified by PD-L1 TPS (< 1% vs ≥ 1%), taxane (paclitaxel
vs nab-paclitaxel), region (east Asia vs other)
Carboplatin AUC 6 Q3W, nab-paclitaxel 100 mg/m2 QW, paclitaxel 200 mg/m2 Q3W, pembrolizumab 200 mg Q3W.
*Upon confirmation of PD and safety criteria by BICR, optional crossover could occur during combination or monotherapy.
Placebo + Carboplatin +
Paclitaxel or nab-Paclitaxel
3-wk cycles x 4
(n = 281)
Pembrolizumab
up to 31 cycles
Placebo
up to 31 cycles
Pembrolizumab
up to 35 cycles
Crossover
allowed*
PD

4. KEYNOTE-407: Baseline Characteristics
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com
Characteristic Pembro + Chemo (n = 278) Chemo (n = 281)
Median age, yrs (range) 65 (29-87) 65 (36-88)
Male, n (%) 220 (79.1) 235 (83.6)
ECOG PS 1, n (%) 205 (73.7) 191 (68.0)
Stable brain metastases, n (%) 20 (7.2) 24 (8.5)
Former/current smoker, n (%) 256 (92.1) 262 (93.2)
Enrolled in east Asia, n (%) 54 (19.4) 52 (18.5)
PD-L1 TPS ≥ 1%, n (%) 176 (63.3) 177 (63.0)
Paclitaxel chosen as taxane, n (%) 169 (60.8) 167 (59.4)
Prior thoracic radiation, n (%) 17 (6.1) 22 (7.8)
Prior (neo)adjuvant therapy, n (%) 5 (1.8) 8 (2.8)

5. KEYNOTE-407: PFS by RECIST v1.1 (BICR) in ITT Population
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Reproduced with permission. Slide credit: clinicaloptions.com
Mos
Patients at Risk, n
PFS(%)
Median PFS, Mos (95% CI)
6.4 (6.2-8.3)
4.8 (4.3-5.7)
100
80
60
40
20
0
0 3 6 9 12 15 18 21
Pembro + Chemo
Chemo
54.7
70.1
0.56
(0.45-0.70)
< .0001
Events, % HR (95% CI) P Value
278
281
223
190
142
90
57
26
23
12
5
4
0
0
0
0

6. KEYNOTE-407: OS in ITT Population
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Reproduced with permission. Slide credit: clinicaloptions.com
Mos
Patients at Risk, n
OS(%)
Median OS, Mos (95% CI)
15.9 (13.2-NE)
11.3 (9.5-14.8)
100
80
60
40
20
0
0 3 6 9 12 15 18 21
Pembro + Chemo
Chemo
30.6
42.7
0.64
(0.49-0.85)
0.0008
Events, % HR (95% CI) P Value
278
281
256
246
188
175
124
93
62
45
17
16
2
4
0
0

7. KEYNOTE-407: OS in Key Subgroups
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Reproduced with permission. Slide credit: clinicaloptions.com
Subgroup
Overall
Age
< 65 yrs
≥ 65 yrs
Sex
Male
Female
ECOG PS
0
1
Region of enrollment
East Asia
Rest of world
Choice of taxane
Paclitaxel
Nab-paclitaxel
Deaths/Patients,
n/N
205/559
88/254
117/305
167/455
38/104
48/163
157/396
34/106
171/453
140/336
65/223
0.64 (0.49-0.85)
0.52 (0.34-0.80)
0.74 (0.51-1.07)
0.69 (0.51-0.94)
0.42 (0.22-0.81)
0.54 (0.29-0.98)
0.66 (0.48-0.90)
0.44 (0.22-0.89)
0.69 (0.51-0.93)
0.67 (0.48-0.93)
0.59 (0.36-0.98)
HR (95% CI)
Chemo BetterPembro + Chemo Better
0.1 0.5 1

8. KEYNOTE-407: PFS, OS by PD-L1 TPS
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com
Survival by PD-L1 Expression,
Mos (95% CI)
Pembro + Chemo Chemo HR (95% CI)
Median PFS by RECIST v1.1 (BICR)
 TPS < 1%
 TPS 1% to 49%
 TPS ≥ 50%
6.3 (6.1-6.5)
7.2 (6.0-11.4)
8.0 (6.1-10.3)
5.3 (4.4-6.2)
5.2 (4.2-6.2)
4.2 (2.8-4.6)
0.68 (0.47-0.98)
0.56 (0.39-0.80)
0.37 (0.24-0.58)
Median OS
 TPS < 1%
 TPS 1% to 49%
 TPS ≥ 50%
15.9 (13.1-NE)
14.0 (12.8-NE)
NR (11.3-NE)
10.2 (8.6-13.8)
11.6 (8.9-17.2)
NR (7.4-NE)
0.61 (0.38-0.98)
0.57 (0.36-0.90)
0.64 (0.37-1.10)
Pembro + chemo: TPS < 1%, n = 95; TPS 1% to 49%, n = 103; TPS ≥ 50%, n = 73.
Chemo: TPS < 1%, n = 99; TPS 1% to 49%, n = 104; TPS ≥ 50%, n = 73.

9. KEYNOTE-407: Secondary Endpoints
 Median follow-up: 7.8 mos (0.1-19.1)
 Mean treatment duration
‒ Pembro + chemo: 6.3 mos
‒ Chemo: 4.7 mos
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com
Response
Pembro +
Chemo
(n = 278)
Chemo
(n = 281)
ORR, % (95% CI)
57.9
(51.9-63.8)
38.4
(32.7-44.4)
CR, n (%) 4 (1.4) 6 (2.1)
PR, n (%) 157 (56.5) 102 (36.3)
SD, n (%) 78 (28.1) 104 (37.0)
PD, n (%) 17 (6.1) 39 (13.9)
Not evaluable,* n (%) 6 (2.2) 7 (2.5)
Not assessed,† n (%) 16 (5.8) 23 (8.2)
*Patients with ≥ 1 post-BL imaging assessment but none evaluable per
RECIST v1.1 (BICR). †Patients without ≥ 1 post-BL imaging assessment.
Outcome
Pembro +
Chemo
(n = 161)
Chemo
(n = 108)
Median DoR, mos
(range)
7.7
(1.1+ to 14.7+)
4.8
(1.3+ to 15.8+)

10. KEYNOTE-407: Safety
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com
Summary of AE, n (%) Pembro + Chemo (n = 278) Chemo (n = 280)
All cause 273 (98.2) 274 (97.9)
Grade 3-5 194 (69.8) 191 (68.2)
Led to death
 Treatment related
23 (8.3)
10 (3.6)
18 (6.4)
6 (2.1)
Led to discontinuation
 All treatment
 Any treatment
37 (13.3)
65 (23.4)
18 (6.4)
33 (11.8)
Immune-mediated and infusion reactions
 Grade 3-5
 Led to death
80 (28.8)
30 (10.8)
1 (0.4)
24 (8.6)
9 (3.2)
1 (0.4)

11. KEYNOTE-407: AEs
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Reproduced with permission. Slide credit: clinicaloptions.com
All-Cause AEs Occurring in ≥ 20% of Patients Immune-Mediated AEs and Infusion Reactions
Pembro + Chemo
Chemo
Grade
1-2 3-5
Frequency, %
0 5 10 15 20 25 30 35 40 45 50 55 60
Anemia
Alopecia
Neutropenia
Nausea
Thrombocytopenia
Diarrhea
Decreased Appetite
Constipation
Fatigue
Asthenia
Arthralgia
Peripheral neuropathy 16.1
20.5
20.5
14.3
21.1
21.6
25.7
22.7
21.8
23.0
29.3
24.5
23.2
29.9
23.2
30.6
32.1
35.6
32.9
37.8
36.4
46.0
51.8
53.2
Frequency, %
0 1 2 3 4 5 6 7 8 9 10
Hypothyroidism
Hyperthyroidism
Pneumonitis
Infusion reactions
Colitis
Hepatitis
Severe skin reactions
Hypophysitis
Thyroiditis
Nephritis
1.8
7.9
0.7
7.2
2.1
6.5
2.1
2.9
1.4
2.5
0
1.8
0.4
1.8
1.1
0
1.1
0
0.7
0.7

12. KEYNOTE-407: Conclusions
 In patients with untreated metastatic squamous NSCLC, addition of pembrolizumab to
carboplatin + paclitaxel or nab-paclitaxel significantly improved survival regardless of PD-L1
expression level
‒ Median PFS: 6.4 vs 4.8 mos (P < .0001); median OS: 15.9 vs 11.3 mos (P = .0008)
 ORR, DoR also improved with addition of pembrolizumab to chemotherapy in this setting
 Safety profile consistent with known data for regimen constituents
‒ D/c rates for AEs low overall but numerically higher in pembrolizumab arm
‒ Immune-mediated AEs also more common in pembrolizumab arm; frequency/severity comparable
to studies with pembrolizumab monotherapy
 Study investigators suggest that pembrolizumab + carboplatin + paclitaxel or nab-paclitaxel
should be a standard frontline treatment for metastatic squamous NSCLC with any PD-L1 TPS
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com

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