1. Improved Survival With Nivolumab vs Docetaxel in Pts With Advanced Squamous Cell NSCLC After Platinum-Containing Chemotherapy: CheckMate 017
Slideset on: Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373:
This activity is supported by educational grants from Genentech, Lilly, and Novartis.

2. About These Slides
Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent
These slides may not be published or posted online without permission from Clinical Care Options (
Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. Background: Nivolumab in Metastatic NSCLC
Few therapeutic options available for the ~ 30% of pts diagnosed with advanced squamous cell NSCLC[1]
Nivolumab: fully human IgG4 anti–PD-1 monoclonal antibody
May restore antitumor immune response[2]
Showed antitumor activity in pts with previously treated advanced squamous-cell NSCLC in phase I, II studies[3,4]
CheckMate 057 showed survival advantage with nivolumab over docetaxel in pts with previously treated nonsquamous NSCLC[5]
Current study, CheckMate 017, compared nivolumab vs docetaxel in pts with advanced, previously treated squamous-cell NSCLC[1]
NSCLC, non-small-cell lung cancer.
1. Brahmer J, et al. N Engl J Med. 2015;373:
2. Brahmer JR, et al. J Clin Oncol. 2010;28:
3. Gettinger SN, et al. J Clin Oncol. 2015;33:
4. Rizvi NA, et al. Lancet Oncol. 2015;16:
5. Borghaei H, et al. N Engl J Med. 2015;373:
Slide credit: clinicaloptions.com

4. CheckMate 017: Phase III Study Schema
Stratified by prior paclitaxel (yes vs no) and geographic region (US/Canada vs Europe vs rest of world)
Treatment continued until PD or unacceptable AE;
Pts receiving nivolumab could continue beyond progression based on investigator’s discretion
Nivolumab 3 mg/kg IV q2w*
(n = 135)
Stage IIIB or IV or recurrent squamous-cell NSCLC after 1 prior platinum-containing chemotherapy regimen*
(N = 272)
Docetaxel 75 mg/m2 q3w*
(n = 137)
EGFR, epidermal growth factor receptor; IV, intravenous; NSCLC, non-small-cell lung cancer; OS, overall survival; q2w, every 2 weeks; q3w, every 3 weeks.
*Prior maintenance therapy allowed, including EGFR tyrosine kinase inhibitor.
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

5. Overall Survival (% of Patients)
CheckMate 017: OS
OS significantly longer with nivolumab vs docetaxel; benefit seen in most subgroups*
100 80 60 40 20
Median OS, mo (95% CI) 9.2 ( ) 6.0 ( )
1-Yr OS, % of pts (95% CI) 42 (34-50)
24 (17-31)
No. of Deaths
Nivolumab (N = 135) Docetaxel (N = 137)
HR: 0.59 (95%CI: ) P < .001
Overall Survival (% of Patients)
CI, confidence interval; HR, hazard ratio; mOS, median OS; OS, overall survival. 3 6 9 12 15 18 21 24
Mos
*Except for pts outside US, Europe and those aged ≥ 75 yrs
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

6. CheckMate 017: PFS
PFS significantly longer with nivolumab vs docetaxel
100 80 60 40 20
Median PFSS, mo (95% CI) 3.5 ( ) 2.8 ( )
1-Yr PFS, % of pts (95% CI) 21 (14-28)
6 (3-12)
No. of Events
Nivolumab (N = 135) Docetaxel (N = 137)
HR: 0.62 (95% CI: ) P < .001
PFS (% of Patients)
CI, confidence interval; HR, hazard ratio; mPFS, median PFS; PFS, progression-free survival 3 6 9 12 15 18 21 24
Mos
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

7. CheckMate 017: Other Efficacy Outcomes
Secondary efficacy outcomes favored nivolumab vs docetaxel
ORR (20% vs 9%; P = .008)
Median duration of response (not reached vs 8.4 mos)
Proportion of responders with ongoing response (63% vs 33%)
PD-L1 expression not prognostic or predictive
No difference in nivolumab benefit based on PD-L1 expression
PD-L1 expression assessed with validated automated IHC assay using clone 28-8 (a rabbit monoclonal antihuman PD-L1 antibody)
ORR, objective response rate; PD-L1, programmed death ligand-1.
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

8. Nivolumab in Squamous NSCLC: OS by PD-L1 Expression Level
mOS, Mos
Nivo
Doc
PD-L1 ≥ 1%
9.3
7.2
PD-L1 < 1%
8.7
5.9
mOS, Mos
Nivo
Doc
PD-L1 ≥ 5% 10
6.4
PD-L1 < 5%
8.5
6.1
mOS, Mos
Nivo
Doc
PD-L1 ≥ 10% 11
7.1
PD-L1 < 10%
8.2
6.1
100 90 80 70 60
OS (%) 50 40 30
NSCLC, non-small-cell lung cancer. 20 10 3 6 9 12 15 18 21 24 3 6 9 12 15 18 21 24 3 6 9 12 15 18 21 24
Mos
Mos
Mos
Nivolumab PD-L1+
Nivolumab PD-L1-
Docetaxel PD-L1+
Docetaxel PD-L1-
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

9. CheckMate 017: Most Common AEs
Most common treatment-related AEs*, n (%)
Nivolumab (n = 131)
Docetaxel (n = 129)
Any Grade
Grade 3/4
Grade 3/4†
Any
76 (58)
9 (7)
111 (86)
71 (55)
Fatigue
21 (16)
1 (1)
42 (33)
10 (8)
Decreased appetite
14 (11)
25 (19)
Asthenia
13 (10)
18 (14)
5 (4)
Nausea
12 (9)
30 (23)
2 (2)
Diarrhea
26 (20)
3 (2)
Arthralgia
7 (5)
Pyrexia
6 (5)
Pneumonitis
AE, adverse event.
*In ≥ 5% of pts in nivolumab arm.
†Treatment with docetaxel also resulted in 3 grade 5 AEs, including interstitial lung disease, pulmonary hemorrhage, and sepsis (n = 1 each).
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

10. CheckMate 017: Select Tx-Related AEs
Select treatment-related
AEs, n (%)
Nivolumab (n = 131)
Docetaxel (n = 129)
Any Grade
Grade 3/4
Skin
12 (9)
11 (9)
2 (2)
Gastrointestinal
Diarrhea
Colitis
11 (8)
10 (8)
1 (1)
26 (20)
3 (2)
Pulmonary
Pneumonitis
Lung infiltration
Interstitial lung disease
7 (5)
6 (5)
1 (1)*
Endocrine
5 (4)
Renal
4 (3)
Hepatic
Hypersensitivity/infusion rxn
AE, adverse event.
*Grade 5 event.
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

11. Conclusions and Faculty Assessment
Nivolumab conferred significant survival benefit over docetaxel for pts with previously treated squamous-cell NSCLC
Median OS, 9.2 vs 6.0 mos (P < .001)
Median PFS, 3.5 vs 2.8 mos (P < .001)
ORR higher with nivolumab vs docetaxel (20% vs 9%; P = .008)
Treatment-related grade 3/4 AEs less common with nivolumab vs docetaxel (7% vs 55%)
Nivolumab represents a new standard of care for treatment of patients with squamous-cell NSCLC after therapy with a platinum-based chemotherapy regimen
AE, adverse event; NSCLC, non-small-cell lung cancer; ORR, overall response rate; OS, overall survival; PD-L1, programmed death ligand-1; PFS, progression-free survival.
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

12. Conclusions and Faculty Assessment
No association between PD-L1 expression and nivolumab benefit
Weaknesses of this study:
Interpretation of subgroup analyses limited by small patient numbers, statistical factors, imbalance in ECOG PS favoring docetaxel in older patients
Assessment of PD-L1 is not a perfect biomarker for predicting efficacy of nivolumab in this setting, and additional research is needed
Future directions:
Explore role of nivolumab as first-line therapy for squamous NSCLC
Using combination approaches: immunotherapy combinations, immunotherapy plus targeted agents
Explore optimal use of PD-L1, and other biomarkers, to select pts mostly likely to benefit from nivolumab
ECOG PS, Eastern Cooperative Oncology Group performance status; NSCLC, non-small-cell lung cancer; OS, overall survival; PD-1, programmed death ligand-1.
Slide credit: clinicaloptions.com
Brahmer J, et al. N Engl J Med. 2015;373:

13. Go Online for More CCO Coverage of Immunotherapy!
Downloadable resource summarizing current treatment of NSCLC Downloadable slidesets of key data A CME-certified text module on immunotherapy with expert faculty commentary on key studies
clinicaloptions.com/oncology