KEY TAKEAWAYS
- The ALTER-G-001 phase 2 trial aimed to evaluate the efficacy and safety of combining anlotinib with first-line chemo in the treatment of LMs GI tumors.
- The primary endpoint was ORR.
- The result concluded that anlotinib + chemo shows positive initial results in controlling LMs CRC tumors.
Advanced gastrointestinal (GI) tumors encompassing colorectal (CRC), gastric (GC), and pancreatic cancers (PC), as well as esophageal squamous cell carcinoma (ESCC), a substantial 20%-50% grapple with the challenge of liver metastases (LMs). The prognosis takes a somber turn for CRC burdened with unresectable LMs, showcasing a dismal 5-year survival rate below 5%. However, a glimmer of hope emerges from prior trials unveiling the compelling clinical potential and well-tolerated safety profile of anlotinib paired with chemotherapy (chemo) in the advanced stages of CRC and ESCC, particularly in the presence of LMs.
This intriguing backdrop underscored the need for novel therapeutic approaches to transform the landscape of treatment for these formidable GI malignancies. Herein, Junwei Wu and other researchers conducted an evaluation of the effectiveness and safety of utilizing anlotinib in combination with chemo as the initial treatment for GI tumors with LMs.
In the interventional study, patients (pts) diagnosed with unresectable GI tumors featuring LMs and lacking prior systemic interventions were stratified into three cohorts: Cohort A (CRC), Cohort B (ESCC), and Cohort C (other GI tumors, e.g., PC, GC, etc.). In Cohort A, CRC pts underwent induction therapy (6 cycles, every 3 weeks) comprising anlotinib (12 mg, orally, once daily, days 1-14), oxaliplatin (130 mg/m2, intravenously, day 1), and capecitabine (850 mg/m2, orally, twice daily, days 1-14).
Patients exhibiting non-progressive disease (PD) and undergoing radical resection received maintenance therapy with anlotinib and metronomic capecitabine (500 mg, orally, twice daily, days 1-21, every 3 weeks) until PD or intolerable toxicity. The primary endpoint was the objective response rate (ORR) based on RECIST 1.1 criteria. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), radical resection rate for LMs, and safety assessment.
The results showed that Cohort A comprised 45 enrolled patients, with a median age of 67 years (range 35-75), consisting of 66.7% males, and 91.1% presenting with ECOG performance status 1; 60% exhibited solely LMs. Following induction therapy, 7 patients underwent surgical resection. Presently, 26 patients are still undergoing treatment, including 8 on maintenance therapy, with a maximum treatment duration of 12.8 months.
Among the 35 assessable patients in cohort A, the ORR and DCR stood at 54.3% and 97.1%, respectively (partial response (PR), n=19; stable disease(SD), n=15, with 13 instances demonstrating reduced tumor size). The median PFS has not been reached. About 34 patients experienced treatment-emergent adverse events (TEAEs), with grade 3 TEAEs observed in 33.3% of cases, primarily including neutropenia (11.1%), hypertension (6.7%) and decreased white blood cell count (6.7%).
The study concluded that combining anlotinib with chemo as the initial treatment demonstrates promising efficacy and acceptable safety and emerges as a potentially favorable choice for advanced colorectal tumors with LMs.
This study is sponsored by Ruijin Hospital.
Clinical Trial: https://clinicaltrials.gov/study/NCT05262335
Wu J, Zhu L, Zhou C, et al. “Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort A.” Presented at ESMO Asia Congress 2023. (Abstract: 103P).
