Start Your Search
MA14 - The Adequate MTarget Is Still the Issue (ID 140)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
MA14.05 - A Randomized Phase III Trial of Fruquintinib Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (FALUCA) (Now Available) (ID 1490)
15:45 - 17:15 | Author(s): Li Liang
Fruquintinib, an orally active kinase inhibitor that selectively targets vascular endothelial growth factor (VEGF) receptor, demonstrated significant benefit in progression-free survival and disease control in a randomized Phase II study in patients with non-small-cell lung cancer (NSCLC) who had failed two lines of chemotherapy. This Phase III FALUCA trial is a randomized, double-blind, placebo-controlled, multicenter trial designed to confirm the efficacy in the same patient population (NCT02691299).Method
From December 2015 to February 2018, 45 clinical centers across China participated in the trial. A total of 730 patients aged 18-75 with advanced NSCLC who had failed two lines of chemotherapy were screened and 527 who met the eligibility criteria were enrolled into the study. Patients were stratified based on epidermal growth factor receptor mutation status and prior use of VEGF inhibitor therapy, and were randomized in a 2:1 ratio to receive fruquintinib (n=354) or placebo (n=173) once daily in a 3 weeks on/1 week off 4-week cycle. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response. The final data cutoff was on September 21, 2018.Result
Median OS was 8.94 months for fruquintinib and 10.38 months for placebo (hazard ratio, 1.02; 95% CI, 0.816 to 1.283; p=0.841). Median PFS was 3.68 months for fruquintinib comparing to 0.99 months for placebo, respectively (hazard ratio, 0.34; 95%CI, 0.279 to 0.425; p<0.001). The ORR and DCR were 13.8% and 66.7% for fruquintinib, compared with 0.6% and 24.9% for placebo (both p<0.001), respectively. The most frequent treatment-emergent adverse events with fruquintinib (≥grade 3) were hypertension (20.7%), hand-foot syndrome (11.0%), and proteinuria (1.4%). A sensitivity analysis revealed that median OS was significantly prolonged with fruquintinib compared with placebo in patients who received no subsequent systemic anti-tumor therapies (7.00 months versus 5.06 months ; hazard ratio, 0.64; 95%CI, 0.453 to 0.903; p=0.010).Conclusion
The FALUCA trial failed to meet the primary end point of OS while confirming significant benefit in secondary end points including PFS, ORR and DCR. The safety profile of fruquintinib in this patient population was acceptable and consistent with that identified in the Phase II study. A post-hoc sensitivity analysis revealed that the anti-tumor therapies that patients received post disease progression probably contributed to the failure of this study on the primary end point.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
P1.14-16 - Resolving Resistance to Osimertinib by Combining Apatinib and Osimertinib in EGFR-Mutant NSCLC Patients (ID 860)
09:45 - 18:00 | Author(s): Li Liang
There are currently limited treatment options after osimertinib resistance.Resistance to epidermal growth factor receptor(EGFR) inhibitors is frequently associated with enhanced vascular endothelial growth factor(VEGF) levels.Dual inhibition of the VEGF receptor(VEGFR) and EGFR signaling pathways has the potential to overcome osimertinib resistance. Apatinib is an oral tyrosine kinase inhibitor(TKI) against VEGFR-2. This study was conducted to evaluate the efficacy of Apatinib plus osimertinib after osimertinib resistance in EGFR-mutant NSCLC patients.Method
The study was expected to enroll 30 EGFR-mutant NSCLC patients resistant to osimertinib. Patients received oral apatinib 250mg QD plus osimertinib 80mg qd. Efficacy evaluation was conducted after first month, then every two months once again. The primary endpoint was progression free survival (PFS).Result
From March 01, 2018 to February 28, 2019, 23 patients were enrolled. The overall response rate(ORR) and disease control rate(DCR)of apatinib plus osimertinib after osimertinib resistance was 8.7%(2/23) and 73.9%(17/23),respectively.Until the last follow-up(March 31,2019), 17 patients (73.9%,17/23)showed disease progression,the other 6 patients (26.1%,6/23) still received combination therapy,as shown in figure 1.The median PFS was 4.0 months (95% CI 2.4-5.5).Six patients had received at least six-month combination therapy,four of whom were still on treatment.The most common adverse event was hypertension, diarrhea,rash and hand-foot syndrome.What calls for special attention is that one patient achieved partial response, however, stopped the combination therapy due to seriously decreased left ventricular ejection fraction.
Apatinib plus osimertinib might be a choice after osimertinib resistance.For further investigation, large sample and additional clinical trials are warranted.