New FDA Approvals for Cancer Treatment in September 2022
In September, the US FDA approved five new indications for cancer management.
- Futibatinib for Metastatic Cholangiocarcinoma. Accelerated approval was granted for the highly selective, irreversible FGFR1-4 inhibitor futibatinib (Lytgobi, Taiho Oncology, Inc.) for adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma (iCCA) harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions/rearrangements. This approval was based on efficacy results from the multicenter, open-label, single-arm TAS-120-101 (FOENIX-CCA2) trial, which included 103 patients with locally advanced or metastatic iCCA with FGFR2 fusions/rearrangements, detected by next-generation sequencing (NGS). At the primary analysis, the objective response rate (ORR) was 41.7%, with a median duration of response (DoR) of 9.7 months. Analysis after an additional 8 months of follow-up (25 months) confirmed the durable efficacy and continued tolerability of futibatinib observed at the primary analysis in previously treated patients with advanced iCCA with FGFR2 fusion/rearrangement. Of note, 74% of responses lasted for 6 months or more.
- Durvalumab for Metastatic Biliary Tract Cancer. Approval was granted for durvalumab (Imfinzi, AstraZeneca UK Limited) in combination with gemcitabine and cisplatin for adult patients with locally advanced or metastatic biliary tract cancer (BTC). This approval was based on the double-blind, placebo-controlled, randomized, phase III TOPAZ-1 trial (n=685), which compared durvalumab plus chemotherapy (gemcitabine plus cisplatin) with placebo plus chemotherapy in patients with previously untreated advanced BTC (56% of patients had cholangiocarcinoma, 25% had gallbladder cancer, and 19% had extrahepatic cholangiocarcinoma). The median overall survival (OS) was 12.8 months and 11.5 months in the durvalumab and placebo arms, respectively (hazard ratio [HR], 0.80; P = 0.021). Median progression-free survival (PFS) was 7.2 months in the durvalumab arm vs. 5.7 months with placebo, and investigator-assessed ORR was 27% and 19%, respectively.
- Selpercatinib for Advanced RET Fusion-Positive NSCLC. Regular approval was given for selpercatinib (Retevmo, Eli Lilly and Company) for adult patients with advanced non-small cell lung cancer (NSCLC) with RET gene fusion, as detected by an FDA-approved test. Selpercatinib had previously received accelerated approval for this indication in May 2020. The original approval was based on initial ORR and DoR results from the multicenter, open-label LIBRETTO-001 trial, which included 144 patients. The update to regular approval was based on data from a further 18 months of follow-up of 172 additional patients, giving a total of 316 patients. Among 69 treatment-naïve patients, ORR was 84% with a DoR of 20.2 months. Among 247 patients previously treated with platinum-based chemotherapy, ORR was 61%, with a DoR of 28.6 months. The FDA also approved the Oncomine™ Dx Target Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib.
- Selpercatinib for Advanced RET Fusion-Positive Solid Tumors. Selpercatinib also received accelerated approval for patients with advanced solid tumors with a RET gene fusion that progressed on, or following, prior systemic treatment, or who had no satisfactory alternative treatment options. This approval was based on an interim analysis of ORR and DoR data from the LIBRETTO-001 basket trial, which enrolled 45 patients with RET fusion-positive tumors (other than NSCLC and thyroid cancer) with disease progression on, or following, prior systemic treatment, or who had no satisfactory alternative treatment options. Of the 41 efficacy-evaluable patients, the ORR as per the independent review committee was 43.9% (n = 18).
- Sodium Thiosulfate to Reduce Ototoxicity Risk of Cisplatin in Pediatric Patients With Localized Solid Tumors. Sodium thiosulfate (Pedmark, Fennec Pharmaceuticals Inc.) was given approval for reducing the risk of ototoxicity associated with cisplatin in pediatric patients 1 month and older with localized, non-metastatic solid tumors. Efficacy was evaluated in two multicenter, open-label, randomized controlled trials that included pediatric patients receiving cisplatin-based chemotherapy: SIOPEL 6 and COG ACCL0431. In SIOPEL 6, 114 children with hepatoblastoma received 6 cycles of perioperative cisplatin with or without sodium thiosulfate in various doses. The primary outcome was the percentage of patients with Brock Grade ≥1 hearing loss. The incidence of hearing loss was lower in the sodium thiosulfate and cisplatin arm (39%) compared with the cisplatin alone arm (68%), for an unadjusted relative risk of 0.58. In COG ACCL0431, 125 patients (1 – 18 years old) with solid tumors received cisplatin-based chemotherapy (cumulative dose of cisplatin ≥200 mg/m2), with or without sodium thiosulfate. Efficacy was evaluated in a subset of 77 patients with localized, non-metastatic solid tumors. The incidence of hearing loss, according to American Speech-Language-Hearing Association criteria, was lower in the sodium thiosulfate plus cisplatin arm (44%) compared with the cisplatin alone arm (58%), for an unadjusted relative risk of 0.75. The recommended sodium thiosulfate dose is based on surface area according to actual body weight. Sodium thiosulfate is administered as an intravenous infusion over 15 minutes following cisplatin infusions that are 1 to 6 hours in duration.