Neoadjuvant immunotherapy combined with chemotherapy in the treatment of resectable non-small-cell lung carcinoma: A retrospective cohort study in a single center_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YANG Dongbao ² , ZHONG Kaize ¹ , MA Hongmei ¹ , ZHANG Shifa ¹ , LIU Hongfeng ¹ , CHEN Liji ² , ZHANG Jishen ² ,  CAI Haibo ¹

1. Department of Thoracic Surgery, The First People's Hospital of Jining, Jining, 272000, Shandong, P. R. China;
2. Jining Medical University, Jining, 272000, Shandong, P. R. China;

Corresponding author：

CAI Haibo, Email: 13518670801@163.com

Keywords：

Non-small-cell lung carcinoma; neoadjuvant therapy; immunotherapy; chemotherapy; pathological reaction; surgery

DOI：

10.7507/1007-4848.202406013

Video：

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Objective To evaluate the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced resectable non-small-cell lung carcinoma. Methods The clinical data of patients with non-small cell lung cancer (NSCLC) who received neoadjuvant immunotherapy combined with chemotherapy and surgery after chemotherapy alone from April 2021 to January 2021 in the first People's Hospital, Jining, were retrospectively analyzed. According to the preoperative neoadjuvant regimen, the patients were divided into a combination group and a chemotherapy group, and the clinical data of the two groups were compared. Results A total of 66 patients were enrolled, including 61 males and 5 females. There were 53 patients in the combination group with an average age of 63.40±6.80 years, and 13 patients in the chemotherapy group with an average age of 58.62±8.30 years. There was statistical difference in age between the two groups (P=0.02), but no statistical difference in other baseline data (P＞0.05). MPR was 54.7% in the combination group and 23.1% in the chemotherapy group (P=0.042), and PCR was 39.6% in the combination group and 0.0% in the chemotherapy group (P=0.006). The combined group had a shorter operative time (P=0.039). There were no statistical differences in intraoperative bleeding, postoperative tube-carrying time, postoperative complications, OS or EFS between the two groups. Conclusion Surgery after neoadjuvant immunotherapy is safe and feasible, and long-term efficacy should be confirmed by further follow-up.

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5.	Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med, 2022, 386(21): 1973-1985.
6.	Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med, 2023, 389(6): 491-503.
7.	Heymach JV, Harpole D, Mitsudomi T, et al. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med, 2023, 389(18): 1672-1684.
8.	Cascone T, Awad MM, Spicer JD, et al. LBA1 CheckMate 77T: phase Ⅲ study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage Ⅱ–Ⅲb NSCLC. Annals of Oncology, 2023, 34(suppl_2): S1295.
9.	Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: The neotorch randomized clinical trial. JAMA, 2024, 331(3): 201-211.
10.	Yue D, Wang W, Liu H, et al. LBA58 pathological response to neoadjuvant tislelizumab (TIS) plus platinum-doublet (PtDb) chemotherapy (CT) in resectable stage Ⅱ-ⅢA NSCLC patients (pts) in the phase Ⅲ (Ph3) RATIONALE-315 trial. Annals of Oncology, 2023, 34: S1299.
11.	O'Brien M, Paz-Ares L, Marreaud S, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-ⅢA non-small-cell lung cancer (PEARLS/KEYNOTE-091): An interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol, 2022, 23(10): 1274-1286.
12.	Felip E, Altorki N, Zhou C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage Ⅱ-ⅢA non-small-cell lung cancer (IMpower010): A randomised, multicentre, open-label, phase Ⅲ trial. Ann Oncol, 2023, 34(10): 907-919.
13.	Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage Ⅲ melanoma. Nat Med, 2018, 24(11): 1655-1661.
14.	Lee JM, Tsuboi M, Brunelli A. Surgical perspective on neoadjuvant immunotherapy in non-small cell lung cancer. Ann Thorac Surg, 2022, 114(4): 1505-1515.
15.	Patel SP, Othus M, Chen Y, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med, 2023, 388(9): 813-823.
16.	Lee JM, Kim AW, Marjanski T, et al. Important surgical and clinical end points in neoadjuvant immunotherapy trials in resectable NSCLC. JTO Clin Res Rep, 2021, 2(10): 100221.
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18.	Sun C, Liu Y, Zhang P, et al. Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage ⅢA/ⅢB non-small cell lung cancer: A single-arm, phase 2 trial. J Cancer Res Clin Oncol, 2023, 149(2): 819-831.
19.	Spicer J, Forde PM, Provencio M, et al. Clinical outcomes with neoadjuvant nivolumab (N) + chemotherapy (C) vs C by definitive surgery in patients (pts) with resectable NSCLC: 3-y results from the phase 3 CheckMate 816 trial. J Clin Oncol, 2023, 41(suppl_16): 8521-8521.
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22.	Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected egfr-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
23.	Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell, 2021, 39(2): 154-173.
24.	Ricciuti B, Wang X, Alessi JV, et al. Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels. JAMA Oncol, 2022, 8(8): 1160-1168.
25.	Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015, 348(6230): 124-128.
26.	Castellanos E, Snider J, Ali SM, et al. Tumor mutational burden (TMB) and PD-L1 expression as predictors of response to immunotherapy (IO) in NSCLC. J Clin Oncol, 2019, 37(suppl_15): 2630.
27.	Felip E, Srivastava M, Reck M, et al. MA11. 08 IMpower010: Exploratory analysis of tumour mutational burden and disease-free survival with adjuvant atezolizumab in NSCLC. J Thorac Oncol, 2023, 18(suppl_11): S139.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol, 2016, 11(1): 39-51.
3. NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: A systematic review and meta-analysis of individual participant data. Lancet, 2014, 383(9928): 1561-1571.
4. Pless M, Stupp R, Ris HB, et al. Induction chemoradiation in stage ⅢA/N2 non-small-cell lung cancer: A phase 3 randomised trial. Lancet, 2015, 386(9998): 1049-1056.
5. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med, 2022, 386(21): 1973-1985.
6. Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med, 2023, 389(6): 491-503.
7. Heymach JV, Harpole D, Mitsudomi T, et al. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med, 2023, 389(18): 1672-1684.
8. Cascone T, Awad MM, Spicer JD, et al. LBA1 CheckMate 77T: phase Ⅲ study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage Ⅱ–Ⅲb NSCLC. Annals of Oncology, 2023, 34(suppl_2): S1295.
9. Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: The neotorch randomized clinical trial. JAMA, 2024, 331(3): 201-211.
10. Yue D, Wang W, Liu H, et al. LBA58 pathological response to neoadjuvant tislelizumab (TIS) plus platinum-doublet (PtDb) chemotherapy (CT) in resectable stage Ⅱ-ⅢA NSCLC patients (pts) in the phase Ⅲ (Ph3) RATIONALE-315 trial. Annals of Oncology, 2023, 34: S1299.
11. O'Brien M, Paz-Ares L, Marreaud S, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-ⅢA non-small-cell lung cancer (PEARLS/KEYNOTE-091): An interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol, 2022, 23(10): 1274-1286.
12. Felip E, Altorki N, Zhou C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage Ⅱ-ⅢA non-small-cell lung cancer (IMpower010): A randomised, multicentre, open-label, phase Ⅲ trial. Ann Oncol, 2023, 34(10): 907-919.
13. Blank CU, Rozeman EA, Fanchi LF, et al. Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage Ⅲ melanoma. Nat Med, 2018, 24(11): 1655-1661.
14. Lee JM, Tsuboi M, Brunelli A. Surgical perspective on neoadjuvant immunotherapy in non-small cell lung cancer. Ann Thorac Surg, 2022, 114(4): 1505-1515.
15. Patel SP, Othus M, Chen Y, et al. Neoadjuvant-adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med, 2023, 388(9): 813-823.
16. Lee JM, Kim AW, Marjanski T, et al. Important surgical and clinical end points in neoadjuvant immunotherapy trials in resectable NSCLC. JTO Clin Res Rep, 2021, 2(10): 100221.
17. Lei J, Zhao J, Gong L, et al. Neoadjuvant camrelizumab plus platinum-based chemotherapy vs chemotherapy alone for Chinese patients with resectable stage ⅢA or ⅢB (T3N2) non-small cell lung cancer: The TD-FOREKNOW randomized clinical trial. JAMA Oncol, 2023, 9(10): 1348-1355.
18. Sun C, Liu Y, Zhang P, et al. Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage ⅢA/ⅢB non-small cell lung cancer: A single-arm, phase 2 trial. J Cancer Res Clin Oncol, 2023, 149(2): 819-831.
19. Spicer J, Forde PM, Provencio M, et al. Clinical outcomes with neoadjuvant nivolumab (N) + chemotherapy (C) vs C by definitive surgery in patients (pts) with resectable NSCLC: 3-y results from the phase 3 CheckMate 816 trial. J Clin Oncol, 2023, 41(suppl_16): 8521-8521.
20. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer. N Engl J Med, 2017, 377(20): 1919-1929.
21. Solomon B, Ahn JS, Dziadziuszko R, et al. LBA2 ALINA: Efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC). Ann Oncol, 2023, 34(suppl_2): S1254-S1335.
22. Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected egfr-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
23. Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell, 2021, 39(2): 154-173.
24. Ricciuti B, Wang X, Alessi JV, et al. Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels. JAMA Oncol, 2022, 8(8): 1160-1168.
25. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015, 348(6230): 124-128.
26. Castellanos E, Snider J, Ali SM, et al. Tumor mutational burden (TMB) and PD-L1 expression as predictors of response to immunotherapy (IO) in NSCLC. J Clin Oncol, 2019, 37(suppl_15): 2630.
27. Felip E, Srivastava M, Reck M, et al. MA11. 08 IMpower010: Exploratory analysis of tumour mutational burden and disease-free survival with adjuvant atezolizumab in NSCLC. J Thorac Oncol, 2023, 18(suppl_11): S139.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

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