Table 1 Reported Clinical Activity of Neoadjuvant Trials in Patients with NSCLC

TKI monotherapy

Erlotinib

(56 days)

NCT01217619

II

19

stage

IIIA-N2 EGFR mutation-positive NSCLC

stage

IIIA-N2 EGFR mutation-positive NSCLC

Stage IIIA-N2 EGFR mutation-positive NSCLC

EGFR mutation exon 19 or 21

74% of patients had resection

21.2%

42.1%

11.2

51.6

Xiong L (2019) [55]

Erlotinib

(42 days)

NCT01407822 (EMERGING)

II

72

Stage IIIA-N2 EGFR mutation-positive NSCLC

EGFR mutation exon 19 or 21

84% of patients in the erlotinib arm (64.9% lobectomy; 13.5% bilobectomy; 5.4% pneumonectomy) versus. 68% of patients in the chemotherapy group (54.3% lobectomy; 14.3% bilobectomy; 0% pneumonectomy)

10.8%

54.1%

21.5

45.8

Zhong W (2019) [56]

Crizotinib (median 30 days; range 28–120)

NA

II

11

NSCLC with

N2 disease, no bulky lymph nodes, ALK positive

ALK

ROS1

91% had R0 resection (10

lobectomy and 1 pneumonectomy)

27.3%

No pCR but 90% PR

NA

NA

Zhang C (2019) [57]

Antiangiogenetic inhibitor with chemotherapy

Nintedanib + Cisplatin + Docetaxel

NCT02225405

I/II

21

Stage IB–IIIA

PDGFR

FGFR

VEGFR

FLT3

90% patients had resection (18 R0 and 1 R1 resection). Of the surgeries, 84% lobectomy, 5% lobectomy and wedge, 11% pneumonectomy

30%

66% at 12 mo

91% at 12 mo

Cascone T (2020) [58]

Bevacizumab (56 days) + Cisplatin + Docetaxel (77 days)

NCT00130780

II

50

Stage IB-IIIA

VEGF

82% of patients had resection. Of the surgeries, 9% pneumonectomy, 6% bilobectomy, 4% wedge resection, 81% R0 resection

38%

45%

54

3-year OS was 62%

Chaft J (2013) [59]

ICI with chemotherapy

Cycle 1: Paclitaxel + Cisplatin or Carboplatin

Cycles 2 and 3 Paclitaxel + Cisplatin or Carboplatin + Ipilimumab

(no duration stated)

NCT01820754 (TOP1201 IPI)

II

55

Stage IB, IIA, IIB, or IIIA

CTLA-4

100% of patients had resection in both groups

Ipilimumab group: 100% R0 resections versus. chemotherapy group: 98% R0 resections and 2% R1 resections

38%

15%

Yang C (2018) [60]

Nivolumab + Paclitaxel + Carboplatin (63 days)

Followed by Nivolumab monotherapy for 1 year

NCT03081689

II

46

Stage IIIA

PD-L1

89% of patients had resection

77.1%

at 24 mo

Provencio M (2020) [61]

Nivolumab + platinum doublet versus platinum doublet

NCT02998528 (CheckMate 816)

III

358

Stage IB-IIIA

PD-L1

83% of patients in the Nivolumab group (77% lobectomy and 17% pneumonectomy) versus. 78% of patients in the chemotherapy group (61% lobectomy and 25% pneumonectomy)

Spicer J (2021) [62]

Nivolumab + chemotherapy

NCT03838159 (NADIM II)

II

90

Stage IIIA

PD-L1

92.5% of patients treated with NIVO + chemo had R0 resection versus 65% of patients with chemo

69.8%

36.2%

52%

89.3% at 12 mo. and 66.6% at 24 mo

98.2% at 12 mo. and 84.7% at 24 mo

Provencio M (2022) [63]

ICI monotherapy

Nivolumab

(28 days)

NCT02259621

II

21

Stage I, II, or IIIA

PD-L1

95% of patients had complete tumor resection

40%

45%

Forde PM (2018) [64]

Sintilimab

ChiCTR-OIC-17013726

Ib

40

Stage IA-IIIB

PD-L1

92.5% of patients had resection (60% lobectomies and 32.5% pneumonectomies)

40.5%

Gao S (2020) [65]

Nivolumab or Nivolumab + Ipilimumab

(29 days)

NCT03158129 (NEOSTAR)

II

44

Stage I-IIIA

PD-L1

CTLA-4

95% of patients resected in Nivolumab group; 81% in Nivolumab + Ipilimumab group

Nivolumab: 10%

Nivolumab + ipilimumab: 38%

Nivolumab: 22%

Nivolumab + ipilimumab: 38%

Cascone T (2021) [66]

Nivolumab + Ipilimumab

(42 days?)

NCT02259621

Ib/II

15

Stage IB (≥ 4 cm)-IIIA

PD-L1

CTLA-4

67% patients had definitive resection

33%

50% are disease free

Reuss JE (2020) [67]

Atezolizumab (22 days)

NCT02927301 (LCMC3)

II

101

Stage IB-IIIB

PD-L1

89% of patients had resection

18%

Kwiatkowski DJ (2019) [68]

Pembrolizumab

(42 days)

NCT02938624

I

10

Stage I-II

PD-L1

40%

Bar J (2019) [69]

Atezolizumab (84 days)

NCT02716038

II

30

Stage IB-IIIA

PD-L1

87% of patients had R0

surgical resection. Of the surgical resections, 73% lobectomy, 15% bilobectomy, 12% pneumonectomy)

57%

Shu C (2020) [70]