. 2020 Jul 22;123(6):874–884. doi: 10.1038/s41416-020-0986-4

Table 2.

Summary of data from combination trials of systemic treatments for NSCLC.

Study	Design and setting	Trial arms	N and age (years)	Key findings in older adults
Pembrolizumab plus chemotherapy
KEYNOTE-189 NCT02578680	Phase 3 First line non-squamous PD-L1 (any)	Cisplatin or carboplatin, pemetrexed (maintenance pemetrexed) versus Cisplatin or carboplatin, pemetrexed + pembrolizumab (maintenance pemetrexed + pembrolizumab)	n = 616 (1:2) Median age 64 (range 34–84) Age ≥65: 49%	OS > 65y: HR 0.64 (95% CI 0.43–0.95) OS < 65y: HR 0.43 (95% CI 0.31–0.61)
KEYNOTE-407 NCT02775435	Phase 3 First line squamous PD-L1 (any)	Carboplatin, (nab)-paclitaxel (maintenance pemetrexed) versus Carboplatin, (nab)-paclitaxel + pembrolizumab (maintenance pemetrexed + pembrolizumab)	n = 559 (1:1) Median age 65 (range 29–88) Age ≥65: 55%	OS > 65y: HR 0.74 (95% CI 0.51–1.07) OS < 65y: HR 0.52 (95% CI 0.34–0.80) PFS > 65y: HR 0.63 (95% CI 0.47–0.84) PFS < 65y: HR 0.50 (95% CI 0.37–0.69)
Atezolizumab plus chemotherapy
IMpower150 NCT02366143	Phase 3 First line EGFR/ALK⁺ allowed after >1 TKI non-squamous PD-L1 (any)	Carboplatin, paclitaxel, bevacizumab (maintenance bevacizumab) versus Carboplatin, paclitaxel, bevacizumab + atezolizumab (maintenance bevacizumab + atezolizumab) (versus Carboplatin, paclitaxel, atezolizumab; results from this arm not reported)	n = 800 (1:1) Median age 63 (range 31–90) Age ≥65: 45%	PFS ≥ 75y: HR 0.78 (95% CI NR) PFS 65–74y: HR 0.52 (95% CI NR) PFS < 65y: HR 0.65 (95% CI NR)
IMpower130 NCT02367781	Phase 3 First line EGFR/ALK⁺ allowed after >1 TKI Non-squamous PD-L1 (any)	Carboplatin, nab-paclitaxel, (best supportive care or switch maintenance pemetrexed) versus Carboplatin, nab-paclitaxel + atezolizumab (maintenance atezolizumab)	n = 723 (1:2) Age ≥65: 50%	OS ≥ 65y: HR 0.78 (95% CI 0.58–1.05) OS < 65y: HR 0.79 (95% CI 0.58–1.08) PFS ≥ 65y: HR 0.64 (95% CI 0.50–0.82) PFS < 65y: HR 0.64 (95% CI 0.50–0.82)
IMpower132 NCT02657434	Phase 3 First line Non-squamous PD-L1 (any)	Carboplatin or cisplatin, pemetrexed (maintenance pemetrexed) versus Carboplatin or cisplatin, pemetrexed + atezolizumab (maintenance pemetrexed + atezolizumab)	n = 578 (1:1) Age ≥65: 45%	OS ≥ 65y: HR 0.71 (95% CI 0.50–1.01) OS < 65y: HR 0.89 (95% CI 0.65–1.21) PFS ≥ 65y: HR 0.55 (95% CI 0.42–0.73) PFS < 65y: HR 0.63 (95% CI 0.49–0.80)
IMpower131 NCT02367794	Phase 3 First line squamous PD-L1 (any)	Carboplatin, nab-paclitaxel versus Carboplatin, nab-paclitaxel + atezolizumab (maintenance atezolizumab) (versus Carboplatin, paclitaxel + atezolizumab (maintenance atezolizumab); results from this arm not reported)	n = 1021 (1:1) Median age 65 (range 23–86) Age ≥65: 52%	PFS ≥ 75y: HR 0.51 (95% CI 0.30–0.84) PFS 65–74y: HR 0.66 (95% CI 0.51–0.87) PFS < 65y: HR 0.77 (95% CI 0.61–0.99)
Nivolumab plus Ipilimumab
CheckMate-227 NCT02477826 (Part 1—group PD-L1≥1% only)	Phase 3 First line squamous and non-squamous PD-L1 ≥1%	Nivolumab + Ipilimumab versus platinum-based chemotherapy (versus Nivolumab—not included in primary endpoint analysis)	n = 1189 (1:1:1) Median age 64 (range 26–87) Age ≥65: 49%	OS ≥ 75y: HR 0.92 (95% CI 0.57–1.48) OS 65–74y: HR 0.91 (95% CI 0.70–1.19) OS < 65y: HR 0.70 (95% CI 0.55–0.89)
CheckMate-817 NCT02869789 (Cohorts A and A1)	Phase 3b/4 First line squamous and non-squamous PD-L1 (any)	Nivolumab + Ipilimumab	n = 391 + 198 Median age 65 (range 26–90) Age ≥65: NR	NR
Lung-MAP NCT02785952 Sub-study S1400I	Phase 3 Second line squamous PD-L1 (any)	Nivolumab + Ipilimumab versus Nivolumab	n = 275 (1:1) Median age and range NR Age ≥65: NR	NR
Durvalumab plus Tremelimumab
MYSTIC NCT02453282	Phase 3 First line squamous and non-squamous	(Durvalumab versus) Durvalumab/tremelimumab versus platinum-based chemotherapy	n = 1118 (1:1:1) Median age 65 (range 32–87) Age ≥65: NR	Durvalumab/tremelimumab versus chemotherapy OS ≥ 65y: HR 0.72 (95% CI 0.50–1.02) OS < 65y: HR 1.01 (95% CI 0.70–1.46)

Study

Design and setting

Trial arms

N and age (years)

Key findings in older adults

Pembrolizumab plus chemotherapy

KEYNOTE-189

NCT02578680

Phase 3

First line

non-squamous

PD-L1 (any)

Cisplatin or carboplatin, pemetrexed (maintenance pemetrexed) versus Cisplatin or carboplatin, pemetrexed + pembrolizumab (maintenance pemetrexed + pembrolizumab)

n = 616 (1:2)

Median age 64 (range 34–84)

Age ≥65: 49%

OS > 65y: HR 0.64 (95% CI 0.43–0.95)

OS < 65y: HR 0.43 (95% CI 0.31–0.61)

KEYNOTE-407

NCT02775435

Phase 3

First line

squamous

PD-L1 (any)

Carboplatin, (nab)-paclitaxel (maintenance pemetrexed) versus Carboplatin, (nab)-paclitaxel + pembrolizumab (maintenance pemetrexed + pembrolizumab)

n = 559 (1:1)

Median age 65 (range 29–88)

Age ≥65: 55%

OS > 65y: HR 0.74 (95% CI 0.51–1.07)

OS < 65y: HR 0.52 (95% CI 0.34–0.80)

PFS > 65y: HR 0.63 (95% CI 0.47–0.84)

PFS < 65y: HR 0.50 (95% CI 0.37–0.69)

Atezolizumab plus chemotherapy

IMpower150

NCT02366143

Phase 3

First line

EGFR/ALK⁺ allowed after >1 TKI

non-squamous

PD-L1 (any)

Carboplatin, paclitaxel, bevacizumab (maintenance bevacizumab) versus Carboplatin, paclitaxel, bevacizumab + atezolizumab (maintenance bevacizumab + atezolizumab) (versus Carboplatin, paclitaxel, atezolizumab; results from this arm not reported)

n = 800 (1:1)

Median age 63 (range 31–90)

Age ≥65: 45%

PFS ≥ 75y:

HR 0.78 (95% CI NR)

PFS 65–74y:

HR 0.52 (95% CI NR)

PFS < 65y:

HR 0.65 (95% CI NR)

IMpower130

NCT02367781

Phase 3

First line

EGFR/ALK⁺ allowed after >1 TKI

Non-squamous

PD-L1 (any)

Carboplatin, nab-paclitaxel, (best supportive care or switch maintenance pemetrexed) versus Carboplatin, nab-paclitaxel + atezolizumab (maintenance atezolizumab)

n = 723 (1:2)

Age ≥65: 50%

OS ≥ 65y:

HR 0.78 (95% CI 0.58–1.05)

OS < 65y:

HR 0.79 (95% CI 0.58–1.08)

PFS ≥ 65y:

HR 0.64 (95% CI 0.50–0.82)

PFS < 65y:

HR 0.64 (95% CI 0.50–0.82)

IMpower132

NCT02657434

Phase 3

First line

Non-squamous

PD-L1 (any)

Carboplatin or cisplatin, pemetrexed (maintenance pemetrexed) versus Carboplatin or cisplatin, pemetrexed + atezolizumab (maintenance pemetrexed + atezolizumab)

n = 578 (1:1)

Age ≥65: 45%

OS ≥ 65y:

HR 0.71 (95% CI 0.50–1.01)

OS < 65y:

HR 0.89 (95% CI 0.65–1.21)

PFS ≥ 65y:

HR 0.55 (95% CI 0.42–0.73)

PFS < 65y:

HR 0.63 (95% CI 0.49–0.80)

IMpower131

NCT02367794

Phase 3

First line

squamous

PD-L1 (any)

Carboplatin, nab-paclitaxel versus Carboplatin, nab-paclitaxel + atezolizumab (maintenance atezolizumab) (versus Carboplatin, paclitaxel + atezolizumab (maintenance atezolizumab); results from this arm not reported)

n = 1021 (1:1)

Median age 65 (range 23–86)

Age ≥65: 52%

PFS ≥ 75y: HR 0.51 (95% CI 0.30–0.84)

PFS 65–74y: HR 0.66 (95% CI 0.51–0.87)

PFS < 65y: HR 0.77 (95% CI 0.61–0.99)

Nivolumab plus Ipilimumab

CheckMate-227

NCT02477826 (Part 1—group PD-L1≥1% only)

Phase 3

First line

squamous and non-squamous

PD-L1 ≥1%

Nivolumab + Ipilimumab versus platinum-based chemotherapy (versus Nivolumab—not included in primary endpoint analysis)

n = 1189 (1:1:1)

Median age 64 (range 26–87)

Age ≥65: 49%

OS ≥ 75y:

HR 0.92 (95% CI 0.57–1.48)

OS 65–74y:

HR 0.91 (95% CI 0.70–1.19)

OS < 65y: HR 0.70 (95% CI 0.55–0.89)

CheckMate-817

NCT02869789

(Cohorts A and A1)

Phase 3b/4

First line

squamous and non-squamous

PD-L1 (any)

Nivolumab + Ipilimumab

n = 391 + 198

Median age 65 (range 26–90)

Age ≥65: NR

Lung-MAP

NCT02785952

Sub-study S1400I

Phase 3

Second line

squamous

PD-L1 (any)

Nivolumab + Ipilimumab versus Nivolumab

n = 275 (1:1)

Median age and range NR

Age ≥65: NR

Durvalumab plus Tremelimumab

MYSTIC

NCT02453282

Phase 3

First line

squamous and non-squamous

(Durvalumab versus) Durvalumab/tremelimumab versus platinum-based chemotherapy

n = 1118 (1:1:1)

Median age 65 (range 32–87)

Age ≥65: NR

Durvalumab/tremelimumab versus chemotherapy

OS ≥ 65y: HR 0.72 (95% CI 0.50–1.02)

OS < 65y: HR 1.01 (95% CI 0.70–1.46)

CI confidence interval, IQR interquartile range, HR hazard ratio, NR not reported, OS overall survival, PD-L1 programmed cell death ligand 1, PFS progression-free survival, TKI tyrosine kinase inhibitor, y years.