Neoadjuvant treatment in non-small cell lung cancer: New perspectives with the incorporation of immunotherapy

Table 1 Clinical evidence for neoadjuvant immunotherapy in non-small cell lung cancer

Study	Phase	Stages	Treatment	Cycles	Patients included	Main endpoint	ORR	MPR	pCR
Forde et al[8]	I	I-IIIA	Nivolumab	2	21	Safety and feasibility	10%	45%	10%
LCMC3[14]	II	IB-IIIB	Atezolizumab	2	181	MPR	7%	20%	7%
NEOSTAR[18]	II	I-IIIA	Nivolumab vs nivolumab + ipilimumab1	3	44	MPR	22% vs 19%	24% vs 50%	10% vs 38%
Gao et al[15]	IB	IA-IIIB	Sintilimab	2	40	Safety	20%	40%	16%
NEOMUN[16]	II	II-IIIA	Pembrolizumab	2	15	Safety and feasibility	28%	27%	13%
IONESCO[17]	II	IB-IIIA	Durvalumab	3	46	% R0	8%	18%	7%
Shu et al[19]	II	IB-IIIA	Atezolizumab + carboplatin + nab-paclitaxel	4	30	MPR	63%	57%	33%
NADIM[20]	II	IIIA	Nivolumab + carboplatin + paclitaxel	3	46	PFS 24 mo	76%	83%	63%
SAK 16/14[21]	II	IIIA	Cisplatin + docetaxel followed by durvalumab2	2	62	DFS 12 mo	58%	60%	18%

¹Nivolumab x3 cycles with or without a single dose of ipilimumab.

²Cisplatin + docetaxel x3 cycles followed by 2 cycles of durvalumab. ORR: Objective response rate; MPR: Major pathological response; pCR: Pathological complete response; % R0: % complete resection; PFS 24 mo: Progression-free survival at 24 mo; DFS 12 mo: Disease-free survival at 12 mo.

Table 2 Ongoing clinical trials of neoadjuvant therapy

Treatment strategy	Study number (name)	Phase	Treatment
Anti-PD-1 + chemotherapy	NCT03838159 (NADIM II)	Phase 2 randomised	3 cycles of carboplatin + paclitaxel +/- nivolumab → surgery → 6 mo of adjuvant nivolumab (experimental arm)
	NCT04728724	Phase 2	Grupo A: sintilimab 2-4 cycles → surgery; Group B: sintilimab + chemotherapy (carboplatin + pemetrexed/gemcitabine/paclitaxel) 2-4 cycles → surgery
	NCT04326153	Phase 2	2 cycles of sintilimab + carboplatin + nab-paclitaxel → surgery → 8 cycles of sintilimab
	NCT04379739	Phase 2	2-4 cycles of camrelizumab + apatinib or camrelizumab + chemotherapy (carboplatin + pemetrexed/ gemcitabine) → surgery
	NCT04061590	Phase 2	2 cycles of pembrolizumab + chemotherapy (cisplatin + pemetrexed) → surgery
	NCT04638582	Phase 2	3 cycles of pembrolizumab +/- chemotherapy (carboplatin + pemetrexed/paclitaxel) → surgery
	NCT04025879	Phase 3	chemotherapy +/- nivolumab → surgery → adjuvant nivolumab (experimental arm)
	NCT02998528 (CheckMate 816)	Phase 3	3 cycles of chemotherapy (platinum doublet) + nivolumab → surgery +/- adjuvant chemotherapy (one experimental arm)
Anti-PD-L1 + chemotherapy	NCT04646837	Phase 2	2 cycles of chemotherapy (platinum-based + nab-paclitaxel) + durvalumab → surgery → durvalumab 1 yr
Anti-PD-L1 + anti-CTLA-4	NCT02998528 (CheckMate 816)	Phase 3	3 cycles of nivolumab + 1 cycle of ipilimumab → surgery +/- adjuvant chemotherapy (one experimental arm)
Anti-PD-1	NCT03197467 (NEOMUN)	Phase 2	2 cycles of pembrolizumab → surgery
Anti-PD-1 + anti-LAG3	NCT04205552 (NEOpredict)	Phase 2	2 cycles of nivolumab +/- relatlimab → surgery
Anti-PD-L1 + radiotherapy	NCT04245514	Phase 2	3 cycles of chemotherapy → 1 cycle durvalumab + radiotherapy → surgery → durvalumab 1 yr
	NCT03237377	Phase 2	2 cycles of durvalumab +/- tremelimumab (antiCTLA-4) + radiotherapy → surgery → adjuvant chemotherapy
	NCT03871153	Phase 2	Carboplatin + paclitaxel + radiotherapy + durvalumab → surgery → durvalumab 1 yr