First-Line Treatment of NSCLC - ICI-Chemo vs Dual ICI Combinations

1. First-Line Treatment of NSCLC:
ICI-Chemo vs Dual ICI Combinations
Jarushka Naidoo, MBBCh, MHS
Consultant Medical Oncologist
Beaumont RCSI Cancer Centre
Dublin, Ireland
Adjunct Assistant Professor of Oncology
Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University
Bloomberg-Kimmel Institute for Cancer Immunotherapy
Baltimore, MD
1

2. Trial Comparison Selection ORR, %
PFS
HR
OS HR
KEYNOTE-189
Pembro or placebo +
carbo/pem
PD-L1 unselected;
nonsq
48.3 vs
19.9
0.49 0.56
IMpower130
Atezo + carbo/nab-pac vs
CT alone
PD-L1 unselected;
nonsq
49.2 vs
31.9
0.64 0.79
IMpower150
Atezo + carbo/pac + bev vs
CT + bev
PD-L1 unselected;
nonsq
63.5 vs
48.0
0.62 0.80
KEYNOTE-407
Pembro or placebo +
carbo/pac or nab-pac
PD-L1 unselected; sq
62.6 vs
38.8
0.59 0.71
Single IO-Chemo Combinations in Advanced NSCLC
atezo, atezolizumab; bev, becacizumab; carbo, carboplatin; chemo, chemotherapy; CT, chemotherapy; HR, hazard ratio; IO, immunotherapy; ipi, ipilimumab; nab-pac,
nab-paclitaxel; nonsq, nonsquamous; NSCLC, non-small-cell lung cancer; ORR, objective response rate; OS, overall survival; pac, paclitaxel; pem, pemetrexed; pembro,
pembrolizumab; PFS, progression-free survival; sq, squamous;
Gadgeel SM, et al. J Clin Oncol. 2019;37(15_suppl):9013; Cappuzzo F, et al. Ann Oncol. 2018;29(8):LBA53; Socinski MA, et al. J Clin Oncol.
2018;(15_suppl):9002; Paz-Ares L, et al. J Thorac Oncol. 2020;15(10):1657-69.
OS benefit across all subgroups, regardless of PD-L1

3. KEYNOTE-189: Pembrolizumab + Chemotherapy
Non-Squamous NSCLC
CI, confidence interval; ITT, intent-to-treat; Mo, months; Pbo, placebo.
Gadgeel SM, et al. J Clin Oncol. 2019;37(15_suppl):9013.

4. IMpower-150: Atezolizumab + Chemotherapy + Bevacizumab
Non-Squamous NSCLC
CI, confidence interval; ITT, intent-to-treat; Mo, months; Pbo, placebo.
Socinski MA, et al. J Thorac Oncol. 2021;16(11):1909-24.
19.5 mo

5. IMpower-130: Atezolizumab + Carboplatin + Nab-Paclitaxel
Non-Squamous NSCLC
West H, et al. Lancet Oncol. 2019;20(7):924-37.

6. KEYNOTE-407: Pembrolizumab + Chemotherapy
Squamous NSCLC

7. PD-L1 and TMB:
Do they factor into our choice of chemo-IO?
No
OS benefit across all subgroups
1.Rodriguez-Abreu. ASCO 2020. Abstr 9582. 2. Rodríguez-Abreu. Ann Oncol. 2021;32:881. 3. Garassino. ASCO 2020. Abstr 9521.

8. Trial Comparison Selection ORR, %
PFS
HR
OS HR
CM-227 Nivo + Ipi vs. CT alone
PD-L1 unselected
All histologies
35.9% vs.
30%
0.79 0.73
CM-9LA Nivo + Ipi + CT vs. CT alone
PD-L1 unselected;
All histologies
38,2% vs.
24.9%
0.70 0.69
POSEIDON Durva + Treme + CT vs. CT alone
PD-L1 unselected;
nonsq*
0.74 0.86
Dual IO Combinations in Advanced NSCLC
OS benefit across all subgroups, regardless of PD-L1

9. CM-227: Nivolumab + Ipilimumab vs Chemo in
Advanced NSCLC

10. CM-227: Nivolumab + Ipilimumab vs Chemo in
Advanced NSCLC

11. CM 9LA: Ipi/Nivo+Chemo vs. Chemo in 1L NSCLC
Reck et al, ASCO 2021
Key Eligibility Criteria
• Stage IV or recurrent NSCLC
• No prior systemic therapy
• No sensitizing EGFR
mutations or known ALK
alterations
• ECOG PS 0–1
Stratified by
PD-L1b (< 1%c vs ≥ 1%),
sex, and histology (SQ vs NSQ)
R
1:1
n = 358
n = 361 NIVO 360 mg Q3W + IPI 1 mg/kg Q6W
+
Chemod Q3W (2 cycles)
Chemod Q3W (4 cycles)
with optional pemetrexed maintenance (NSQ)
Until disease
progression,
unacceptable toxicity,
or for 2 years
for immunotherapy
N = 719
Primary Endpoint:
OS

12. PD-L1 >=1%
• Median OS 15.8 vs. 10.9mos; HR 0.70
• DOR: 11.8 vs. 5.6 mos. (33% v. 13%)
Efficacy by PD-L1 Status
Reck et al, ASCO 2021

13. PD-L1 >=1%
• Median OS 15.8 vs. 10.9mos; HR 0.70
• DOR: 11.8 vs. 5.6 mos. (33% v. 13%)
PD-L1 <1%
• Median OS: 17.7 vs. 9.8 mos
• DOR: 17.3 vs. 4.3 mos (45% v. 0%)
Efficacy by PD-L1 Status
Reck et al, ASCO 2021

14. POSEIDON: Durva + Treme + Chemo vs. Chemo in
Advanced NSCLC

15. Immunotherapy Combinations in NSCLC
Deciding between Single IO/Chemo and Dual IO
Tumor Histology PD-L1 status
Oncogenic driver
mutation
Desire to receive
chemotherapy
vs. not
Reasons to avoid
IO: autoimmune
conditions,
transplant
ECOG PS
Patient
preference