Dataset Information

Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA.

ABSTRACT: Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov).

SUBMITTER: Tsuboi M

PROVIDER: S-EPMC8530153 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for <i>EGFR</i>-mutated resectable non-small-cell lung cancer: NeoADAURA.

Tsuboi Masahiro M Weder Walter W Escriu Carles C Blakely Collin C He Jianxing J Dacic Sanja S Yatabe Yasushi Y Zeng Lingmin L Walding Andrew A Chaft Jamie E JE

Future oncology (London, England) 20210719 31

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in pa ...[more]

PMID: 34278827

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Project description:BackgroundA single-agent of anti programmed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapy has been explored for resectable lung cancer before surgery. However, the effectiveness and safety of neoadjuvant programmed cell death 1 (PD-1) blockade combined with chemotherapy have not been published.MethodsTwenty-one consecutive patients with potentially resectable squamous cell carcinoma of the lung who received neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were included in this study. Eight patients received two cycles of neoadjuvant platinum-based doublet chemotherapy combined with anti-programmed cell death 1 (anti-PD-1) therapy, while 13 patients received two cycles of neoadjuvant platinum-based doublet chemotherapy only. Chest computed tomography was repeated before neoadjuvant treatment and surgery. Adverse events were monitored. The major pathological response (MPR) rate was determined after surgery. Selected specimens were sent for immunohistochemical and multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing.ResultsCompared with neoadjuvant chemotherapy alone, the combination of PD-1 blockade and chemotherapy increased the pathological complete response rate (37.5% vs. 7.69%) and MPR rate (50% vs. 38.46%). The pathological and radiological evaluations are not consistent. No unknown adverse effects were reported for all the patients. More tumor infiltrating lymphocytes were observed in patients who received PD-1 blockade. No unknown pathological features associated with PD-1 blockade were found. Immune suppression in the peritumoral spaces around the residual tumor cells was observed. The amino acid sequences of the T-cell receptors are not significantly shared among the patients.ConclusionsThe combination of neoadjuvant chemotherapy and PD-1 blockade is safe and feasible, and might indicate an increased MPR and pathological complete response rate. More investigations are needed for the best combination of the neoadjuvant therapy.

Project description:BackgroundWe compared the real-world efficacy and safety of neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with stage III non-small-cell lung cancer (NSCLC).Participants and methodsA total of 59 consecutive patients were finally selected and divided into two groups: the neoadjuvant chemotherapy group (n = 33) and the neoadjuvant chemoimmunotherapy group (n = 26). The primary endpoint was disease-free survival (DFS). The secondary endpoints were pathological response, clinical response, and adverse events. All patients were followed up to collect perioperative pathology and clinical data.ResultsThe objective response rate (ORR), pathological complete response (pCR), and major pathological response (MPR) were significantly higher in the neoadjuvant chemoimmunotherapy group than in the neoadjuvant chemotherapy group (73.1% vs. 45.5%, 34.6% vs. 3.0%, and 65.3% vs. 15.1%, respectively; P < 0.05). There was no statistically significant difference in disease-free survival between the neoadjuvant chemoimmunotherapy and neoadjuvant chemotherapy groups (P = 0.129). Patients in the neoadjuvant chemoimmunotherapy group had a higher rate of tumor regression than those in neoadjuvant chemotherapy group (37.0% [25 patients] vs. 29.0% [33 patients], P = 0.018). However, no discernible correlation between MPR achievement and the degree of tumor shrinkage was observed in either group (P > 0.05). The cumulative MPR rates were 42.3, 50, and 65.3% for 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemoimmunotherapy group and 9.1, 12.1, and 15.1% for ≤ 2, 3, and ≥ 4 cycles, respectively, in the neoadjuvant chemotherapy group. Moreover, No statistical difference was observed between the two groups regarding postoperative complications, resection range, operation time, surgical method, and extent of resection (P > 0.05). Although the incidence of grades III-IV adverse events was higher in the neoadjuvant chemotherapy group than in the neoadjuvant chemoimmunotherapy group (33.3% vs. 4.6%, P = 0.042), there was no significant difference in the incidence of adverse events between the two groups (64.6% vs. 83.6%, P = 0.072).ConclusionIn stage III NSCLC, neoadjuvant chemoimmunotherapy achieved higher pathological and clinical remission rates than chemotherapy alone, with compromising safety, making it an attractive choice for neoadjuvant therapy.

Dataset Information

Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA.

Publications

Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for <i>EGFR</i>-mutated resectable non-small-cell lung cancer: NeoADAURA.

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