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Table 1. Actively recruiting clinical trials of neoadjuvant immunotherapy before surgery
National clinical Patient Expected
trial number Country number Intervention drug Study design completion date
NCT03871153 [43] USA 25 Durvalumab (anti PD-1) Multi-institutional single arm phase II trial April 2022
in Stage III (N2) NSCLC to trial concurrent
chemoradiation plus Durvalumab
induction then surgery then Durvalumab
NCT03838159 [44] Spain 90 Nivolumab (anti PD-1) Randomized, two-arm, Phase II trial in September 2027
Stage III NSCLC comparing Nivolumab
with carboplatin and Paclitaxel then
surgery then adjuvant Nivolumab vs.
chemotherapy then surgery
NCT03197467 [45] Germany 30 Pembrolizumab (anti PD-1) Single arm, prospective phase II of 2022
Stage II/IIIA NSCLC of neoadjuvant
pembrolizumab then surgery
NCT03237377 [46] USA 32 Durvalumab (anti PD-1) Pilot, non-randomized study of Stage IIIA 2021
NSCLC of Durvalumab with or without
standard thoracic radiation given prior
to surgery and followed by adjuvant
chemotherapy if deemed appropriate
NCT04025879 [47] 113 international 452 Nivolumab (anti PD-1) Phase III, randomized, double-blind 2024
locations trial for resectable Stage II-IIIB NSCLC
of neoadjuvant chemotherapy with or
without Nivolumab followed by surgery
and then adjuvant Nivolumab or placebo
NCT02994576 [48] France 60 Atezolizumab (anti PD-L1) Single arm, phase II trial of Atezolizumab 2022
as induction therapy for Stage IB-IIIA
Non-N2 resectable and untreated NSCLC
NCT03732664 [49] China 40 Nivolumab (anti PD-1) Single arm, feasibility study of neoadjuvant 2027
Nivolumab then surgery for Stage IA3 to
IIIA NSCLC
NCT02259621 [50] USA 30 Nivolumab (anti PD-1) Single arm trial of neoadjuvant Nivolumab 2023
Ipilimumab (CTLA-4 with or without ipilimumab for Stage I to
activation) IIIA, no N3, NSCLC

NCT03158129 [51] USA 66 Nivolumab (anti PD-1) Randomized, phase II trial of Nivolumab 2022
Ipilimumab (CTLA-4 with or without Ipilimumab then standard
activation) induction chemotherapy before surgery
for Stage I-IIIA NSCLC
NSCLC: non-small cell lung cancer; PD-(L)1: programmed cell death protein (ligand) 1; CTLA-4: cytotoxic T-lymphocyte-associated
protein 4

FUTURE DIRECTIONS
Immunotherapy, alone or in combination with traditional chemoradiotherapy, is emerging as one of
the next frontiers alongside different methodologies of radiation treatment that could change surgical
[42]
management of locally advanced NSCLC . There are currently multiple ongoing trials examining the use
of immunotherapy regimens for NSCLC [Table 1] [43-51] . However, there remains a lack of evidence regarding
the safety of pulmonary resection after immunotherapy with only one retrospective study examining
surgery after immunotherapy and a Cochrane review on immunotherapy after surgery [9,18] .

CONCLUSION
The treatment of locally advanced NSCLC continues to evolve. Work is ongoing regarding immunotherapy
and the best approach: neoadjuvant vs. adjuvant treatment. Additionally, minimally invasive surgical
methods continue to evolve and become refined as surgeons increase their experience and technology
improves. Although open thoracotomy has previously been the standard for locally advanced NSCLC,
VATS is slowly becoming more common as studies show similar long-term outcomes and equivalent
or better perioperative outcomes. In our own, unpublished experience, we observed similar rates of
complications versus open surgery and shorter length of stay as previously reported but a better rate of
[52]
proceeding on to adjuvant therapy holding with the concept of faster recovery for less invasive surgery .