Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience

Eichhorn, Florian; Klotz, Laura V.; Kriegsmann, Mark; Bischoff, Helge; Schneider, Marc A.; Muley, Thomas; Kriegsmann, Katharina; Haberkorn, Uwe; Heußel, Claus Peter; Savai, Rajkumar; Zoernig, Inka; Jaeger, Dirk; Thomas, Michael; Hoffmann, Hans; Winter, Hauke; Eichhorn, Martin

doi:10.1016/j.lungcan.2021.01.018

Cited by 58 publications

(62 citation statements)

References 39 publications

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“…25 II Single-arm cohort study 30 30/43/27 Pembrolizumab Two cycles 200 mg IV Q3W Safety, feasibility Eichhorn et al. 14 II Single-arm cohort study 15 0/40/60 Pembrolizumab Two cycles 200 mg IV Q3W Safety, feasibility Lee et al. 18 II Single-arm cohort study 181 9/41/49 Atezolizumab Two cycles 1200 mg IV Q3W MPR Gao et al.…”

Section: Resultsmentioning

confidence: 99%

“…25 , n (%) 7/25 (28) 3/25 (12) Eichhorn et al. 14 , n (%) 4/15 (27) 2/15 (13) Lee et al. 18 , n (%) 30/147 (20) a 10/147 (7) a Gao et al.…”

Section: Resultsmentioning

confidence: 99%

“… 13 The monotherapy–ICI group shows consistent rates of pCR ranging from 0% 28 to 16%, 16 with one study reporting a pCR rate for half the patients achieving MPR. 14 The addition of ipilimumab to nivolumab led to an absolute increase of pCR, with reported rates of 33% and 38%. 20 , 27 Combining chemoradiotherapy with durvalumab led to pCR rate of 27%.…”

Section: Resultsmentioning

confidence: 99%

“…25 , n (%) 5/30 (17) 1/25 (4) 1/30 (3) Eichhorn et al. 14 , n (%) 0/15 (0) 1/15 (7) a 3/15 (20) Lee et al. 18 , n (%) 29/181 (16) 19/159 (12) b 9/181 (5) f Gao et al.…”

Section: Resultsmentioning

confidence: 99%

“…From the 1023 records, 866 were excluded based on title and abstract and another 137 due to ineligibility, leaving 20 articles with a total of 1066 patients for inclusion. These 20 articles represent 15 single-arm cohort studies 11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26] and four randomized studies with two arms. 10,12,[27][28][29] The PRISMA flowchart depicting study selection is presented in Figure 1.…”

Section: Study Screening and Selectionmentioning

confidence: 99%

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Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review

Ulas

Dickhoff²,

Schneiders

et al. 2021

ESMO Open

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Background The neoadjuvant use of immune checkpoint inhibitors (ICIs) in resectable non-small-cell lung cancer (NSCLC) is currently an area of active ongoing research. The place of neoadjuvant ICIs in the treatment guidelines needs to be determined. We carried out a systematic review of published data on neoadjuvant ICIs in resectable NSCLC to study its efficacy and safety. Patients and methods A literature search was carried out using the MEDLINE (PubMed) and Embase databases to retrieve articles and conference abstracts of clinical trials measuring the efficacy [major pathological response (MPR) and pathological complete response (pCR)] and safety (failure to undergo resection, surgical delay, treatment-related adverse events (trAEs) grade ≥3) of neoadjuvant immunotherapy in resectable NSCLC until July 2021. Results Nineteen studies with a total of 1066 patients were included in this systematic review. Neoadjuvant immunotherapy was associated with improved pathological response rates, especially in combination with chemotherapy. Using mono ICI, dual therapy–ICI, chemoradiation–ICI, radiotherapy–ICI, and chemo–ICI, the MPR rates were 0%-45%, 50%, 73%, 53%, and 27%-86%, respectively. Regarding pCR, the rates were 7%-16%, 33%-38%, 27%, 27%, and 9%-63%, respectively. Safety endpoints using monotherapy–ICI, dual therapy–ICI, chemoradiation–ICI, radiotherapy–ICI, and chemo–ICI showed a failure to undergo resection in 0%-17%, 19%-33%, 8%, 13%, and 0%-46%, respectively. The trAEs grade ≥3 rates were 0%-20%, 10%-33%, 7%, 23%, and 0%-67%, respectively. Conclusion In patients with resectable NSCLC stage, neoadjuvant immunotherapy can improve pathological response rates with acceptable toxicity. Further research is needed to identify patients who may benefit most from this approach, and adequately powered trials to establish clinically meaningful benefits are awaited.

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Section: Resultsmentioning

confidence: 99%

“…25 , n (%) 7/25 (28) 3/25 (12) Eichhorn et al. 14 , n (%) 4/15 (27) 2/15 (13) Lee et al. 18 , n (%) 30/147 (20) a 10/147 (7) a Gao et al.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…25 , n (%) 5/30 (17) 1/25 (4) 1/30 (3) Eichhorn et al. 14 , n (%) 0/15 (0) 1/15 (7) a 3/15 (20) Lee et al. 18 , n (%) 29/181 (16) 19/159 (12) b 9/181 (5) f Gao et al.…”

Section: Resultsmentioning

confidence: 99%

Section: Study Screening and Selectionmentioning

confidence: 99%

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Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review

Ulas

Dickhoff²,

Schneiders

et al. 2021

ESMO Open

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Neoadjuvant immunotherapy for advanced, resectable non–small cell lung cancer: A systematic review and meta‐analysis

Verma

Gay

et al. 2023

Cancer

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Background Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non‐small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD‐guided systematic review and meta‐analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes. Methods Eligibility was resectable stage I–III NSCLC and the receipt of programmed death‐1/programmed cell death ligand‐1 (PD‐L1)/cytotoxic T‐lymphocyte–associated antigen‐4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel–Haenszel fixed‐effect or random‐effect model was used, depending on the heterogeneity (I2). Results Sixty‐six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade ≥3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49–12.97; p < .001), progression‐free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38–0.67; p < .001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36–0.74; p = .0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67–1.52; p = .97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15–0.43; p < .001) and OS (HR, 0.26; 95% CI, 0.10–0.67; p = .005). PD‐L1 expressors (≥1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22–7.03; p = .02). Conclusions In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD‐L1, without increasing toxicities. Plain Language Summary This meta‐analysis of 66 studies showed that neoadjuvant immunotherapy for advanced resectable non‐small cell lung cancer is safe and efficacious. Compared with chemotherapy alone, chemoimmunotherapy improved pathologic response rates and survival, particularly for patients who had tumors that expressed programmed cell death ligand‐1, without increasing toxicities.

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Immunotherapy for Non-small Cell Lung Cancer

Minervini

Boschetti

Pardo

2023

Handbook of Cancer and Immunology

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Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience

Cited by 58 publications

References 39 publications

Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review

Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review

Neoadjuvant immunotherapy for advanced, resectable non–small cell lung cancer: A systematic review and meta‐analysis

Immunotherapy for Non-small Cell Lung Cancer

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