Dataset Information

Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study.

ABSTRACT:

Background

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations.

Methods

This phase 2, single-arm, multicenter trial (ClinicalTrials.gov NCT03736837) was performed at five hospitals in China from December 2018 to November 2020. Non-squamous NSCLC cases with EGFR-sensitizing mutations were treated with anlotinib and icotinib. The primary endpoint was progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity.

Results

Sixty participants were enrolled, including 31 (52%) and 29 (48%) with concurrent mutations and pathogenic concurrent mutations, respectively. The median follow-up was 26.9 (range, 15.0-38.9) months. ORR and DCR were 68.5% and 98.2%, respectively. Median PFS was 15.1 (95%CI: 12.6-17.6) months which met the primary endpoint, median DoR was 13.5 (95%CI: 10.0-17.1) months, and median OS was 30.0 (95%CI: 25.5-34.5) months. Median PFS and OS in patients with pathogenic concurrent mutations were 15.6 (95%CI: 12.5-18.7) months and not reached (95%CI: 17.46 months to not reached), respectively. All patients experienced TRAEs, including 26 (43%) and 1 (1.7%) who had grade ≥ 3 and serious treatment-related adverse events (TRAEs).

Conclusions

Anlotinib combined with icotinib was effective and well-tolerated as a first-line treatment option for EGFR mutation-positive advanced NSCLC with or without concurrent mutations.

Trial registration

ClinicalTrials.gov identifier: NCT03736837.

SUBMITTER: Zhang L

PROVIDER: S-EPMC10403846 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study.

Zhang Linlin L Wang Liuchun L Wang Jingya J Chen Jinliang J Meng Zhaoting Z Liu Zhujun Z Jiang Xiangli X Wang Xinyue X Huang Chun C Chen Peng P Liang Yan Y Jiang Richeng R Wang Jing J Zhong Diansheng D Shang Yanhong Y Zhang Yan Y Zhang Cuiying C Huang Dingzhi D

Molecular cancer 20230805 1

<h4>Background</h4>Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations.<h4>Methods</h4>This phase 2, single-arm, multicenter trial (ClinicalTrials.gov NCT03736837) was performed at five hospitals in China from December 2018 to November 2020. ...[more]

PMID: 37543587

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Project description:BackgroundEpidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.MethodsPatients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS).Results41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.ConclusionsThe results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients.Trial registrationClinicalTrials.gov NCT02430974.

Project description:To explore a better treatment strategy for patients with advanced non-small cell lung cancer harboring sensitive epidermal growth factor receptor mutations, a total of 271 patients were retrospectively analyzed. The patients were divided into two groups: the combination group (58 cases), which received concurrent icotinib, pemetrexed, and platinum treatment, and the sequential group (213 cases), which received the sequential pemetrexed and platinum therapy, followed by icotinib treatment. The primary end points were progression-free survival (PFS) and PFS on the subsequent line of therapy (PFS2). PFS in the combination group was significantly higher compared with that in the sequential group (16.89 months vs. 9.90 months; p < 0.001). PFS in the combination group was also significantly higher than PFS2 in the sequential group (16.89 months vs. 14.05 months; p = 0.009). The overall survival (OS) of the patients was 33.22 months (95% confidence interval (CI): 26.99-37.01) in the combination group and 26.47 months (95% CI: 25.05-26.95) in the sequential group (p < 0.001). The combination group's objective response rate was superior to that of the sequential group (79.31% vs. 52.11%; p < 0.001). Propensity score matching also revealed that icotinib therapy combined with chemotherapy extended the PFS, PFS2, and OS of the patients (p < 0.0001, p = 0.003, and p = 0.001, respectively). The combination group's objective response rate was also better compared with the sequential group (79.31% vs. 51.72%; p = 0.001). In conclusion, our study demonstrated icotinib combined with chemotherapy can improve survival efficacy better than the separated two-line therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? For advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutants, EGFR-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment. Unfortunately, most patients with NSCLC harboring EGFR mutations acquire EGFR-TKI resistance after EGFR-TKI treatment for about 10-14 months. Studies have indicated that chemotherapy plus EGFR-TKIs may have combined effects on the growth of NSCLC cells. However, until now, there has been no study comparing the concurrent and sequential EGFR-TKIs plus chemotherapy. WHAT QUESTION DID THIS STUDY ADDRESS? We retrospectively analyzed the efficacy and safety of concurrent versus sequential icotinib and chemotherapy in untreated NSCLC with sensitive EGFR mutations. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? In the patients with NSCLC with sensitive EGFR mutations, the first-line pemetrexed plus platinum combined with icotinib better improved PFS, PFS2, and objective response rate compared with first-line icotinib and second-line pemetrexed plus platinum. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The results of this paper provide guidance for the strategy choice in the treatment of patients with NSCLC.

Project description:BackgroundThis study aimed to compare the efficacy and safety of different treatment modalities for previously untreated advanced EGFR-mutated non-squamous non-small-cell lung cancer (NSCLC).MethodsThis retrospective study included 196 advanced EGFR-mutated non-squamous NSCLC. 107 received EGFR-tyrosine kinase inhibitor (EGFR-TKI) monotherapy (T), 53 received EGFR-TKI + bevacizumab (T + A), and 36 received EGFR-TKI + bevacizumab + chemotherapy (T + A + C). The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and adverse events (AEs).ResultsThe median PFS was 27 months in the T + A + C group, 17 months in the T + A group, and 10 months in the T group. The multivariate analysis showed lower disease progression in the T + A + C group (HR, 0.377; 95% CI, 0.224-0.634; p < .001). Subgroup analysis showed that the T + A + C group did significantly improve PFS in patients with metastatic organs ≥2, brain metastases, liver metastases, and EGFR 19del compared to T + A group. No significant improvement in OS in the T + A + C group versus the T + A group, but a significant benefit in the subgroup of patients with metastatic organs ≥2. We also performed a subgroup analysis of the T + A + C group versus the T group, which similarly showed that the T + A + C group had better PFS than the T group in most subgroups, and the T + A + C group significantly improved OS in patients with metastatic organ ≥2 and liver metastases compared with the T group. The ORR was significantly higher in the T + A + C group than A + T and T groups (83.3% vs 71.7% vs 60.7%, p = .033). In safety, the T + A + C group had a higher incidence of AEs, but the majority was grade 1-2. The most frequent AEs of grade ≥ 3 were leukopenia (8.3%) and increased aminotransferase (8.3%) in the T + A + C group.ConclusionsFirst-generation EGFR-TKI plus bevacizumab plus chemotherapy was a promising strategy for advanced EGFR-mutated non-squamous NSCLC.

Dataset Information

Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study.

Background

Methods

Results

Conclusions

Trial registration

Publications

Anlotinib plus icotinib as a potential treatment option for EGFR-mutated advanced non-squamous non-small cell lung cancer with concurrent mutations: final analysis of the prospective phase 2, multicenter ALTER-L004 study.

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