Table 2.
Summary of Surgery-Related Details of Ongoing Phase 2 Studies of Neoadjuvant Immunotherapy in Patients With Early NSCLC
| Study ID Trial name Reference(s) |
Stage | Neoadjuvant Therapy | Protocol-Specified Window for Surgery | No. (%) Who Had Surgery/No. of Pts Who Received Neoadjuvant Therapy | Time to Resection | Patients Who Did Not Have Surgery (Reasons) | Preoperative Mortality | Intraoperative Unresectability |
|---|---|---|---|---|---|---|---|---|
| Immunotherapy as monotherapy or dual therapy | ||||||||
|
NCT02927301 LCMC3 Kwiatkowski et al. (2019)32 Lee et al. (2019)21 |
IB–IIIB | Atezolizumab (2 cycles) | Day 40 ± 10 d after first dose of atezolizumab | 90 (89%)/101 | NR Surgery occurred outside 10-d protocol window (range: 2–43 d) in 10% (10 pts): TRAE (n = 2), surgeon availability (n = 2), other (n = 6) |
11/101 (11%) (5/101 [5%; stage IIIA] had preoperative PD, 4/101 [4%] withdrew consent, 1/101 [1%] failed ECG, 1/101 [1%; stage IB] had involvement of pulmonary artery) |
0% | 5/101 (5%); these patients had stage IIIA or IIIB |
|
NCT02994576 PRINCEPS Besse et al. (2020)12 |
I–IIIA | Atezolizumab (1 cycle) | 3 wk after atezolizumab and within <15 d of that window | 30 (100%)/30 | Median, 24 d None delayed >15 d |
0% | 0% | 0% |
|
NCT02259621 CheckMate 159 Bott et al. (2019)41 Forde et al. (2018)14 |
I–IIIA | Nivolumab (3 cycles on d −42, −28, −14 [±2 d] before surgery on d 0) | Approximately 4 wk after the first neoadjuvant dose | 20 (95%)/21 | Median, 18 (range: 11–29) d No treatment-related delays |
0% | 0% | 1/21 (5%) (tracheal invasion; patient had stage IIIA) |
|
NCT03158129 NEOSTAR Cascone et al. (2019)13 Sepesi et al. (2019)33 |
I–IIIA | Nivolumab (3 cycles) vs. nivolumab (3 cycles) + ipilimumab (1 cycle) | Within 3–6 wk after last neoadjuvant dose | 37 (84%)/44 | Median, 31 (range: 21–87) d (n = 8 [22%] delayed beyond 42 d) |
5/44 (11%) N: n = 1 (2%) SAE (grade 3 hypoxia) and high surgical risk NI: n = 4 (9%) PD (1), lack of resectability (1), high surgical risk (1), declined surgery (1) |
1/44 (2%) (pneumonitis and BPF) | NR |
|
NCT02938624 MK3475-223 Bar et al. (2019)24 |
I/II | Pembrolizumab (2 cycles) | 1–3 wk | 13 (87%)/15 | NR 1/13 (8%) had delay owing to treatment-related grade 3 myositis |
2/15 (13%) Treatment-related grade 3 myositis (7%); grade 3 myocardial infarction (7%; not treatment- related) |
NR | NR |
| ChiCTR-OIC-17013726 Gao et al. (2020)23 |
IA–IIIB | Sintilimab (2 cycles) | 29–43 d after first dose of sintilimab | 37 (92.5%)/40 | NR 2/37 (5%) had treatment-related delays (n = 1 grade 2 increased ALT/AST; n = 1 grade 1 hyperthyroidism) |
3/40 (7.5%) | 0% | 0% |
| Combination immunotherapy plus chemotherapy | ||||||||
|
NCT02716038 Columbia Shu et al. (2020)7 |
IB–IIIA | Atezolizumab + carboplatin + nab-paclitaxel (4 cycles) | After computed tomography scan, approximately 4 wk after last dose of chemotherapy Directly to surgery after 2 cycles if computed tomography scan revealed PD |
29 (97%)/30 | Median, 26.5 (IQR: 24–36) d No treatment-related delays |
4/30 (13%) (3/30 [10%] had intraoperative PD; 1/30 [3%] had developed brain metastases) |
0% | 3/30 (10%) |
|
NCT02572843 SAKK 16/14 Rothschild et al. (2020)50 |
IIIA (N2) | Durvalumab (2 cycles) + cisplatin/ docetaxel (3 cycles) | NR | 55 (82%)/67 | NR | 4/67 (6%) had PD before surgery | 1/67 (2%; respiratory failure) | NR |
|
NCT01820754 TOP1201 Yang et al. (2018)22 |
IB–IIIA | Ipilimumab + chemotherapy | Within 12 wk of completing neoadjuvant treatment | 13 (54%)/24 | <12 wk (2 patients [15%] had delay in surgery of 4 and 5 wk, respectively, owing to ipilimumab-related diarrhea) | 11/24 (46%) (persistent N2 cancer: 5/24 [21%]; inadequate pulmonary function: 2/24 [8%]; PD: 2/24 [8%]; location of tumor: 1/24 [4%]; immune-related AE: 1/24 [4%]) |
0% | 0% |
|
NCT03081689 NADIM Provencio et al. (2019)51 |
IIIA | Nivolumab + paclitaxel + carboplatin | Nivolumab + paclitaxel + carboplatin (3 cycles) | 41 (89%)/46 | 3–4 wk after end of neoadjuvant treatment | 5/46 (11%) (patient decision: 4/46 [4%]; did not fulfill resectability criteria: 3/46 [7%]) |
0% | 0% |
|
NCT03366766 Zinner et al. (2020)52 |
I–IIIA | Nivolumab + cisplatin + pemetrexed/gemcitabine (3 cycles) | NR | 13 (100%)/13 | NR | 0% | 0% | NR |
|
NCT02998528 CheckMate 816 Forde et al. (2021)8 Spicer et al. (2021)53 |
IB–IIIA | Nivolumab + pemetrexed+ cisplatin or paclitaxel + carboplatin (nsq) or nivolumab + gemcitabine + cisplatin or paclitaxel + carboplatin (sq) (3 cycles) vs. vinorelbine + cisplatin or gemcitabine + cisplatin (sq only) or pemetrexed + cisplatin (nsq only) or paclitaxel + carboplatin (3 cycles) | Within 6 wk posttreatment | N + chemo: 149 (83%)/176 Chemo: 135 (85%)/176 |
N + chemo: median 5.3 (IQR: 4.6–6.0) wk (n = 31 [21%] delayed beyond 6 wks) Chemo: median 5.0 (IQR: 4.6–5.9) wk (n = 24 [18%] delayed beyond 6 wk) |
N + chemo8: 28 (16%) (disease progression: 12/176 [7%]; AE: 2/176 [1%]; other reason [patient refusal, unresectability, and poor lung function]: 14/176 [8%]) Chemo8: 38 (21%) (disease progression: 17/176 [9%]; AE: 2/176 [1%]; other reason [patient refusal, unresectability, and poor lung function]: 19/176 [11%]) |
N + chemo8: 0%a Chemo8: 3%a (enterocolitis, pneumonia, pancytopenia) |
NR |
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BPF, bronchopleural fistula; chemo, chemotherapy; ECG, electrocardiogram; ID, identifier; IQR, interquartile range; N, nivolumab, NI, nivolumab + ipilimumab; NR, not reported; nsq, nonsquamous; PD, progressive disease; Pt, patient; SAE, serious adverse event; sq, squamous; TRAE, treatment-related adverse event.
a
Describes proportion of patients who experienced treatment-related deaths; includes events reported between the first neoadjuvant dose and 30 days after last dose of neoadjuvant treatment.