Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2)

Zhang, Wei; Deng, Pengbo; Kong, Tiandong; Zhang, Bo; Qian, Fangfei; Dong, Yu; Chen, Ya; Chen, Lu; Liu, Dan-Na; Zhang, Yanwei; Yang, Huanming; Han, Baohui

doi:10.1016/j.lungcan.2022.09.003

Cited by 7 publications

(6 citation statements)

References 17 publications

(21 reference statements)

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“…Consequently, the Chinese Society of Clinical Oncology (CSCO) recommended anlotinib as the only antiangiogenic agent for refractory ES-SCLC in China on August 30, 2019. Furthermore, a prospective study of ACTION-2 reported that EP plus anlotinib regimen as the first-line treatment for ES-SCLC achieved an ORR of 87.2%, a DCR of 97.7%, an mPFS of 9.0 months, and an mOS of 19.0 months (7). A single-arm trial showed that anlotinib plus EP as the first-line treatment for ES-SCLC achieved an ORR of 85.71%, a DCR of 94.29%, an mPFS of 8.02 Changes from baseline in target lesions size (%).…”

Section: Discussionmentioning

confidence: 99%

“…Majority of patients with transformed SCLC after EGFR-TKI resistance of LUAD have received more than one systemic treatment. Furthermore, the combination of anlotinib with EP regimen has been administered as the first-line treatment of extensive-stage SCLC with an objective response rate (ORR) of 87.2% and a median progression-free survival (mPFS) of 9.0 months (7). However, little is known about the efficacy of the combination regimens in transformed SCLC from EGFR-TKIresistant LUAD.…”

Section: Introductionmentioning

confidence: 99%

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Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: a retrospective and observational study

Ding

Leng

Gu³

et al. 2023

Front. Oncol.

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ObjectiveThe histological conversion of lung adenocarcinoma (LUAD) into small-cell lung cancer (SCLC) is an important resistance mechanism for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant LUAD. Anlotinib has been recommended as the third-line treatment for SCLC patients. The efficacy of etoposide/platinum (EP) as the main treatment is very limited for patients with transformed SCLC. However, little is known about EP plus anlotinib for transformed SCLC. The present study retrospectively explored the clinical response to EP combined with anlotinib in patients with transformed SCLC from LUAD after EGFR-TKI failure.MethodsA total of 10 patients who underwent SCLC transformation from EGFR-TKI-resistant LUAD were retrospectively reviewed from September 1, 2019, to December 31, 2022, in three regional hospitals. All of the patients were treated with the combination regimen of EP and anlotinib for four to six cycles, followed by anlotinib maintenance therapy. The clinical efficacy indices including objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and toxicities were evaluated.ResultsThe median time from EGFR-TKI treatment to SCLC conversion was 20.1 ± 2.76 months (17–24 months). Genetic examination after transformation showed that 90% of the patients retained their original EGFR gene mutations. Additional driver genes were found, including BRAF mutation (10%), PIK3CA mutation (20%), RB1 loss (50%), and TP53 mutation (60%). The ORR and DCR were 80% and 100%, respectively. The mPFS was 9.0 months (95% CI, 7.9–10.1 months), and the mOS was 14.0 months (95% CI, 12.0–15.9 months). Less than 10% of grade 3 toxicities were observed, and no grade 4 toxicity and death events were reported.ConclusionThe EP plus anlotinib regimen appears to be a promising and safe strategy in transformed SCLC patients after EGFR-TKI resistance, which warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: a retrospective and observational study

Ding

Leng

Gu³

et al. 2023

Front. Oncol.

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show abstract

“…Consequently, the Chinese Society of Clinical Oncology (CSCO) approved anlotinib as the only antiangiogenic agent for refractory ES-SCLC in China on August 30, 2019. Furthermore, a prospective study of ACTION-2 reported that EP plus anlotinib regimen as the rst-line treatment for ES-SCLC achieved an ORR of 87.2%, a DCR of 97.7%, an mPFS of 9.0 months, and an mOS of 19.0 months (Zhang et al 2022). A single-arm trial showed that anlotinib plus EP as the rst-line treatment for ES-SCLC achieved an ORR of 85.71%, a DCR of 94.29%, an mPFS of 8.02 months, and an mOS of 15.87 months (Deng et al 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Majority of patients with transformed SCLC after EGFR-TKI resistance of LUAD have received more than one systemic treatment. Furthermore, the combination of anlotinib with EP regimen has been administered as the rst-line treatment of extensivestage SCLC with an objective response rate (ORR) of 87.2% and a median progression-free survival (mPFS) of 9.0 months (Zhang et al 2022). However, little is known about the e cacy of the combination regimens in transformed SCLC from EGFR-TKI-resistant LUAD.…”

Section: Introductionmentioning

confidence: 99%

Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: A retrospective and observational study

Ding

Leng

Gu³

et al. 2023

Preprint

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Objective: The histological conversion of lung adenocarcinoma (LUAD) into small-cell lung cancer (SCLC) is an important resistance mechanism for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-resistant LUAD. Anlotinib has been recommended as the third-line treatment for SCLC patients. The efficacy of etoposide/platinum (EP) as the main treatment is very limited for patients with transformed SCLC. However, little is known about EP plus anlotinib for transformed SCLC. The present study retrospectively explored the clinical response to EP combined with anlotinib in patients with transformed SCLC from LUAD after EGFR-TKI failure. Methods: A total of 10 patients who underwent SCLC transformation from EGFR-TKI-resistant LUAD were retrospectively reviewed from September 1, 2019, to December 31, 2022, in three regional hospitals. All of the patients were treated with the combination regimen of EP and anlotinib for four to six cycles, followed by anlotinib maintenance therapy. The clinical efficacy indices including objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and toxicities were evaluated. Results: The median time from EGFR-TKI treatment to SCLC conversion was 20.1±2.76 months (17–24 months). Genetic examination after transformation showed that 90% of the patients retained their original EGFR gene mutations. Additional driver genes included BRAF mutation (10%), PIK3CA mutation (20%), RB1 loss (50%), and TP53 mutation (60%). The ORR and DCR were 80% and 100%, respectively. The mPFS was 9.0 months (95% CI, 7.9–10.1 months), and the mOS was 14.0 months (95% CI, 12.0–15.9 months). Less than 10% of grade 3 toxicities were observed, and no grade 4 toxicity and death events were reported. Conclusion: The EP plus anlotinib regimen appears to be a promising and safe strategy in transformed SCLC patients after EGFR-TKI resistance, which warrants further investigation.

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“…In 2019, CSCO recommended anlotinib as the only antiangiogenic agent for refractory extensive-stage de novo SCLC in China based on the results of the ALTER 1202 study, which compared the efficacy of anlotinib versus placebo, namely, median progression-free survival (mPFS) (4.1 vs. 0.7 months, P < 0.0001) and mOS (7.3 vs. 4.9 months, P = 0.0029) (38). Furthermore, the ACTION-2 study prospectively reported that the first-line treatment with EP plus anlotinib for extensive-stage de novo SCLC achieved an overall response rate (ORR) of 87.2%, a disease control rate (DCR) of 97.7%, an mPFS of 9.0 months, and an mOS of 19.0 months (39). In our retrospective study, transformed SCLC after EGFR-TKI failure was treated with EP plus anlotinib, reaching 9.0 months of mPFS and 14.0 months of mOS (40).…”

Section: Therapeutic Strategies For Sclc Transformed From Nsclc After...mentioning

confidence: 99%

Histological transformation into SCLC: An important resistance mechanism of NSCLC upon immunotherapy

Zeng,

Ding,

Ding

et al. 2023

Front. Immunol.

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The phenomenon of histological transformation has been widely reported in advanced non-small cell lung cancer (NSCLC) with EGFR mutations following the failure of EGFR-TKI treatment. Recent evidence suggests that similar histological changes can also occur in advanced NSCLC without driver gene mutations after developing resistance to immunotherapy. In this review, it was found that 66.7% of cases with immunotherapy-induced histological transformation were classified as lung squamous cell carcinoma (LSCC), while histological conversion into lung adenocarcinoma (LUAD) without EGFR or ALK gene mutations has rarely been reported. There have been sporadic reports on the occurrence of mutual transformation between LUAD and LSCC. The histological conversion from NSCLC into small cell lung cancer (SCLC) appears to be significantly underestimated, likely due to the infrequency of re-biopsy following the development of immunotherapy resistance. Several studies have reported a close association between the transformation and mutations at TP53 and the RB1 splice site, as well as the loss of an FBXW7 mutation. However, the exact mechanisms underlying this conversion remain unclear. Currently, there is a lack of guidelines for the management of transformed SCLC from NSCLC following immunotherapy, with chemotherapy being the most commonly employed treatment approach.

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Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2)

Cited by 7 publications

References 17 publications

Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: a retrospective and observational study

Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: a retrospective and observational study

Etoposide/platinum plus anlotinib for patients with transformed small-cell lung cancer from EGFR-mutant lung adenocarcinoma after EGFR-TKI resistance: A retrospective and observational study

Histological transformation into SCLC: An important resistance mechanism of NSCLC upon immunotherapy

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