Anlotinib plus chemotherapy for T790M‐negative EGFR‐mutant non‐sqNSCLC resistant to TKIs: A multicenter phase 1b/2 trial

Abstract

Background This multicenter phase 1b/2 trial aimed to explore the maximum tolerated dose (MTD), activity, and safety of anlotinib plus chemotherapy in patients with T790M‐negative epidermal growth factor receptor ( EGFR )‐mutant advanced nonsquamous non‐small cell lung cancer (NSCLC) after resistance to first‐ or second‐generation EGFR tyrosine kinase inhibitors (TKIs). Methods In the phase 1b stage, patients received anlotinib (8/10/12 mg, days 1–14) combined with cisplatin (75 mg/m 2 , day 1) or carboplatin (AUC = 5, day 1) plus pemetrexed (500 mg/m 2 , day 1) for a 3‐week cycle based on a 3 + 3 dose‐escalation design. In the phase 2 single‐arm stage, anlotinib was administered at MTD combined with platinum plus pemetrexed for four cycles, followed by anlotinib maintenance therapy. The primary endpoint of the phase 2 stage was progression‐free survival (PFS). Results The study was prematurely terminated due to slow accrual after 19 patients had been enrolled between January 18, 2019, and March 21, 2021. The MTD of anlotinib was 12 mg. The median PFS was 5.75 (95% confidence interval, 4.37–7.52) months. The objective response rate was 47.4% (95% confidence interval, 24.5%–71.1%). In the 12 mg group, seven (58.3%) patients experienced grade 3–4 treatment‐related adverse events, and the most common ones were hypertension (6 [50.0%]), decreased platelet count (2 [16.7%]), and hypertriglyceridemia (1 [8.3%]). No treatment‐related deaths occurred. Conclusion Anlotinib plus platinum and pemetrexed showed promising antitumor activity with manageable toxicity in patients with T790M‐negative EGFR ‐mutant advanced nonsquamous NSCLC after progression on first‐ or second‐generation EGFR TKIs.

Etoposide soft capsule combined with anlotinib in the third-line treatment of advanced non-small cell lung cancer: a retrospective cohort study

“…Anlotinib is an oral small molecule inhibitor of multi-receptor tyrosine kinases, and it targets VEGFR1, VEGFR2, VEGFR3, c-Kit, PDGFR-α, FGFR1, FGFR2, and FGFR3, which can inhibit tumor angiogenesis and cell proliferation ( 14 - 17 ). Wang et al and others have shown that clinically, anlotinib combined with chemotherapy can further improve the efficacy ( 10 , 18 , 19 ). In the study of Zhu et al , it is more cost effective to use anlotinib for patients with advanced NSCLC.…”

Long-term survival in a patient with metastatic parathyroid carcinoma harboring an EGFR sensitizing mutation: a case report

“…Multiple clinical trials are currently underway to assess its efficacy in various malignancies, including non-small cell lung cancer, soft tissue sarcomas, and medullary thyroid carcinoma. 15 – 19 …”

“…Multiple clinical trials are currently underway to assess its efficacy in various malignancies, including non-small cell lung cancer, soft tissue sarcomas, and medullary thyroid carcinoma. [15][16][17][18][19] Herein, we present the case of a patient with recurrent and metastatic PC with an epidermal growth factor receptor (EGFR) p.L858R (c. T2573G)-sensitizing mutation who responded to anlotinib after failure to respond to gefitinib and everolimus. This report provides new insights into the treatment of metastatic PC in clinical practice.…”

Case report: Long-term survival with anlotinib in a metastatic parathyroid carcinoma patient harboring EGFR-sensitizing mutation

“…Anlotinib is a multi-target tyrosine kinase inhibitor (TKI) with potent inhibition activities against VEGFR2/3, FGFR 1-4, PDGFR 𝝰/β, c-Kit, and Ret at the nanomole level. Multiple clinical trials are underway to assess its e cacy in various malignancies, including non-small cell lung cancer (NSCLC), soft tissue sarcomas, and medullary thyroid carcinoma [13][14][15][16][17] .…”