A randomized phase II multi-institutional trial of anlotinib plus docetaxel versus docetaxel in EGFR-wild-type non-small cell lung cancer (NSCLC) patients after progression on first-line platinum-base chemotherapy: ALTER-L018.

Abstract

e21703 Background: Anlotinib is an oral VEGFR, FGFR, PDGFR and c-Kit tyrosine kinase inhibitor, which can prolong both PFS and OS of refractory advanced NSCLC patients in phase III trial: ALTER0303. The combination of docetaxel and ramucirumab/nintedanib had been demonstrated activity in the second line therapy setting for NSCLC. We performed ALTER-L018 to assessed the safety and efficacy of anlotinib with docetaxel in EGFR-wild type refractory advanced NSCLC (NCT03624309). Methods: Patients (pts) with EGFR-wild type refractory advanced NSCLC, who failed to first-line platinum-based chemotherapy, were randomized to group A(anlotinib: 12mg QD from day 1 to 14 of a 21-day cycle +docetaxel: 75mg/m2 Q3W) and group B(docetaxel: 75mg/m2 Q3W). The primary end points is PFS, and secondary end points include OS, ORR, DCR and safety. Results: Between January and December 2019, 36 pts were enrolled at 10 institutions in Hunan China, with 31(15 in group A, 16 in group B) of these individuals being evaluable for treatment efficacy and safety. Pt characteristics(group A/ group B): median age: 55(39-70)/57(44-67); male: 73%/81%; non-squamous NSCLC: 86%/75%. Median PFS were 5.3 months (95%CI:2.76-7.85) in group A and 2.3 months (95%CI, 1.14-3.46) in group B (HR 0.42; 95% CI:0.16-1.13; p = 0.047); In group A and B, ORR and DCR were 26.67% versus 0%(p = 0.043), 60.00% versus 31.25%(p = 0.16), respectively. Among 31 pts, 89% of treatment-related AEs (TRAEs) were grade 1 or 2, and the most common TRAEs in group A were hand-foot syndrome, pruritus and insomnia of 13%(2/15) each; in group B were alopecia, constipation and anemia of 12%(1/16) each. Toxicities≥grade 3(TRAEs) included: neutropenia, leukopenia, diarrhea and hrombocytopenia, 6.6%(1/15) each in group A. There was 1 grade 5 AE in group A. Conclusions: This combination of anlotinib and docetaxel with significant difference PFS prolonging and manageable safety profile, is a viable option in relapsed NSCLC, should be considered following progression on platinum-based chemotherapy. It will be further explored in a randomized phase III trial. Clinical trial information: NCT03624309.

The real-world efficacy and safety of anlotinib in advanced non-small cell lung cancer

“…Generally, the safety profile of anlotinib combination therapy was comparable to that of monotherapy in terms of the frequency of ≥ grade 3 treatment-related adverse events and dose modification. The side effects in our study were in accordance with those in prior studies (Han et al 2018;Huang et al 2020;Wu et al 2020;Zhang et al 2020). There were no new safety concerns or anlotinib-related deaths.…”

“…The efficacy of anlotinib combination therapy in aNSCLC was promising in previous studies, with an ORR of 60-92.6% in the first-line setting and 26-37.5% in the second-line setting (Han et al 2019;Huang et al 2020a;Wu et al 2020). Due to the short follow-up time, the PFS was about 5 months in the patients who received anlotinib plus chemotherapy as ≥ second-line treatment in only two studies (Wu et al 2020;Zhang et al 2020). This was consistent with our study wherein anlotinib combination therapy had a better tumor response than monotherapy in both the treatment-naïve and previously treated patients; this effect was successfully translated into survival benefits in previously treated patients (the survival was immature in treatment-naïve patients).…”

“…The efficacy of anlotinib combination therapy in aNSCLC was promising in previous studies, with an ORR of 60-92.6% in the first-line setting and 26-37.5% in the second-line setting (Han et al 2019;Huang et al 2020a;Wu et al 2020). Due to the short follow-up time, the PFS was about 5 months in the patients who received anlotinib plus chemotherapy as ≥ second-line treatment in only two studies (Wu et al 2020;Zhang et al 2020).…”