Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer

Tfayli, Arafat; Assaad, Majd Al; Fakhri, Ghina; Akel, Reem; Atwi, Hanine; Ghanem, Hady; Karak, Fadi El; Farhat, Fadi; Rabi, Kamal Al; Sfeir, Pierre; Youssef, Pierre; Mansour, Ziad; Assi, Hazem; Haidar, Mohamad; Abi‐Ghanem, Alain S.; Khalifeh, Ibrahim; Boulos, Fouad; Mahfouz, Ramy; Youssef, Bassem; Zeidan, Youssef H.; Bejjany, Rachelle; Khuri, Fadlo R.

doi:10.1002/cam4.3456

Cited by 36 publications

(47 citation statements)

References 18 publications

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“… 19 II Single-arm cohort study 46 0/0/100 Nivolumab Three cycles 360 mg IV Q3W PFS at 24 months Tfayli et al. 24 II Single-arm cohort study 15 c 13/33/54 Avelumab Four cycles 10 mg/kg IV Q2W ORR by RECIST version 1.1 Yang et al. 26 II Single-arm cohort study 24 0/21/79 Ipilimumab Two cycles 10 mg/kg IV Safety, feasibility Chemoradiotherapy with ICI Hong et al.…”

Section: Resultsmentioning

confidence: 99%

“… 27 Regarding the combination of chemoradiotherapy with durvalumab, MPR rate was reported to be 73%. 17 The chemotherapy–ICI group shows higher MPR rates when compared with the monotherapy–ICI group, with rates varying from 27% 24 to 86%. 29 Radiotherapy combined with durvalumab led to MPR in 53% of patients.…”

Section: Resultsmentioning

confidence: 99%

“… 20 , 27 Combining chemoradiotherapy with durvalumab led to pCR rate of 27%. 17 The chemotherapy–ICI group reported rates varying from 9% 24 to 63%, 19 with most studies reporting pCR in more than half of the patients achieving MPR. 10 , 11 , 19 , 22 , 23 , 29 When neoadjuvant durvalumab was combined with radiotherapy, 27% of the included patients achieved pCR.…”

Section: Resultsmentioning

confidence: 99%

“… 19 , n (%) 5/46 (11) 0/41 (0) 14/46 (30) Tfayli et al. 24 , n (%) 4/15 (27) NR 4/15 (27) Yang et al. 26 , n (%) 11/24 (46) 2/13 (15) e 11/24 (46) Chemoradiotherapy with ICI Hong et al.…”

Section: Resultsmentioning

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%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“… 19 , n (%) 5/46 (11) 0/41 (0) 14/46 (30) Tfayli et al. 24 , n (%) 4/15 (27) NR 4/15 (27) Yang et al. 26 , n (%) 11/24 (46) 2/13 (15) e 11/24 (46) Chemoradiotherapy with ICI Hong et al.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Multiple clinical trials are exploring the efficacy of immunotherapy against operable NSCLC in the neoadjuvant setting. Initially, clinical trials examined single‐drug neoadjuvant immunotherapies [46–48] and now recent trials have begun to evaluate neoadjuvant chemoimmunotherapy [49, 50], neoadjuvant immunotherapy plus antiangiogenic therapy [14], and neoadjuvant immunotherapy plus radiotherapy [14, 51]. Current clinical trials on neoadjuvant immunotherapies are mainly single‐arm studies with a small sample [46, 47, 52].…”

Section: Current Clinical Trialsmentioning

confidence: 99%

Neoadjuvant immunotherapy for non–small cell lung cancer: State of the art

Kang

Zhang

Zhong

2021

Cancer Communications

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Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy. Immune checkpoint inhibitors (ICIs) have rapidly evolved from investigational drugs to standard of care for the treatment of metastatic non‐small cell lung cancer (NSCLC). In particular, antibodies that block inhibitory immune checkpoints, such as programmed cell death protein 1 (PD‐1) and programmed cell death 1 ligand 1 (PD‐L1), have revolutionized the treatment of advanced NSCLC, when administered alone or in combination with chemotherapy. Immunotherapy is associated with higher response rates, improved overall survival (OS), and increased tolerability compared with conventional cytotoxic chemotherapy. These benefits may increase the utility of immunotherapy and its combinational use with chemotherapy in the neoadjuvant treatment of patients with NSCLC. Early findings from various ongoing clinical trials suggest that neoadjuvant ICIs alone or combined with chemotherapy may significantly reduce systemic recurrence and improve long‐term OS or cure rates in resectable NSCLC. Here we further summarize the safety and efficacy of various neoadjuvant treatment regimens including immunotherapy from ongoing clinical trials and elaborate the role of neoadjuvant immunotherapy in patients with resectable NSCLC. In addition, we discuss several unresolved challenges, including the evaluations to assess neoadjuvant immunotherapy response, the role of adjuvant treatment after neoadjuvant immunotherapy, the efficacy of treatment for oncogenic‐addicted tumors, and predictive biomarkers. We also provide our perspective on ways to overcome current obstacles and establish neoadjuvant immunotherapy as a standard of care.

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Neoadjuvant Chemoimmunotherapy for NSCLC

Sorin,

Prosty,

Ghaleb

et al. 2024

JAMA Oncol

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ImportanceTo date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non–small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.ObjectiveTo compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.Data SourcesMEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients.Study SelectionObservational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded.Main Outcomes and MeasuresSurgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis.ResultsAmong 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%).Conclusion and RelevanceThis study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.

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Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 36 publications

References 18 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 non–small cell lung cancer: State of the art

Neoadjuvant Chemoimmunotherapy for NSCLC

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