The gastrointestinal (GI) and genitourinary (GU) fields saw over 10 FDA approvals add to their paradigms in 2024, and throughout the year oncologists sat down with OncLive to detail the significance of these regulatory decisions.

The October approval of zolbetuximab-clzb (Vyloy) for patients with HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin 18.2 (CLDN18.2) positive represented the first and only approval of a CLDN18.2-targeted therapy in the US, signifying a key highlight of the year. Another notable advancement came with the expanded approval of lutetium Lu 177 dotatate (Lutathera) for those with rare pediatric somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (NETs).

Tislelizumab-jsgr (Tevimbra) also snagged 2 indications this year, both in the GI space, and nivolumab (Opdivo) received 3 indications in 2024, including 1 approval in the GU field.

Keep reading for all of the FDA approvals from 2024 in GI/GU malignancies with expert commentary sprinkled in:

NALIRIFOX (irinotecan liposome [Onivyde] plus oxaliplatin, fluorouracil, and leucovorin)

Approval type: Regular
Indication: Frontline treatment of patients with metastatic pancreatic adenocarcinoma
Month: February
To read more, visit: bit.ly/4fluRRk

"It’s hard to show improvement in overall survival [OS] in findings from a randomized phase 3 trial in pancreatic cancer—[that] hasn’t been done since the emergence of nab-paclitaxel [Abraxane] and the FOLFIRINOX [leucovorin, fluorouracil, irinotecan, and oxaliplatin] regimen at around the same time. Since then, many studies that have been done in pancreatic cancer failed to meet their end points. The fact that [NAPOLI 3 (NCT04083235)] met its primary end point of OS [with NALIRIFOX vs gemcitabine plus nab-paclitaxel] is significant.”

Zev A. Wainberg, MD
UCLA, Los Angeles, California

Tislelizumab

Approval type: Regular
Indication: Adult patients with unresectable or metastatic esophageal squamous cell carcinoma following prior systemic chemotherapy that did not include a PD-(L)1 inhibitor
Month: March
To read more, visit: bit.ly/4ghWN9V

Lutetium Lu 177 dotatate

Approval type: Expanded
Indication: Pediatric patients 12 years and older
with somatostatin receptor–positive gastroenteropancreatic NETs, including foregut, midgut, and hindgut NETs
Month: April
To read more, visit: bit.ly/3ZW6vJg

"Pediatric NETs are extraordinarily rare—this is a one-in-a-million diagnosis—and the evidence base around therapies for these patients is quite thin. Fortunately, on the adult side, we’ve made a lot of progress over the past 5 or 10 years, and we frequently get questions [from] our pediatric colleagues about what the options are. Given the success of peptide receptor radionuclide therapy for adults, expanding this to children is something that we hope will be helpful.”

Daniel M. Halperin, MD
Winship Cancer Institute of Emory University, Atlanta, Georgia

Adagrasib (Krazati) plus cetuximab (Erbitux)

Approval type: Accelerated
Indication: Adult patients with KRAS G12C–mutant locally advanced or metastatic colorectal cancer (CRC), as determined by an FDA-approved test, who have received prior treatment with fluoropyrimidine-,
oxaliplatin-, and irinotecan-based chemotherapy
Month: June
To read more, visit: bit.ly/4gEHaJr

"With this approval, we have a treatment for patients who have a KRAS G12C mutation within the colorectal tumor. Most directly, it means that those patients have a targeted therapy [option], but it also opens the door to targeting RAS, which is a big goal because KRAS mutations and NRAS mutations are common. Approximately 45% of [patients with] CRC [have KRAS mutations], and this has been a very difficult protein to target, so this is a first step. [Adagrasib] specifically targets the KRAS G12C mutation, [which provides] an option for patients who have that mutation and creates a paradigm to hopefully target more RAS mutations in the future.”

Rona Yaeger, MD
Memorial Sloan Kettering Cancer Center, New York, New York

Zolbetuximab plus fluoropyrimidine- and platinum-containing chemotherapy

Approval type: Regular
Indication: First-line treatment of adult patients with locally advanced unresectable or metastatic, HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive, as determined by an FDA-approved test
Month: October
To read more, visit: bit.ly/4e8f47R

Zanidatamab-hrii (Ziihera)

Approval type: Accelerated
Indication: Previously treated unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) biliary tract cancer, as detected by an FDA-approved test
Month: November
To read more, visit: bit.ly/4ibjIVJ

"This represents the first accelerated approval in biliary tract cancers for a [dual] HER2-targeted [bispecific antibody]. Zanidatamab has shown excellent antitumor activity and tolerability in patients with HER2-amplified biliary tract cancer. It’s extremely exciting and offers a new treatment option for patients with [a] very difficult[-to-treat] disease.”

James J. Harding, MD
Memorial Sloan Kettering Cancer Center, New York, New York

Tislelizumab plus platinum- and fluoropyrimidine-
based chemotherapy

Approval type: Regular
Indication: For the first-line treatment of patients with unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors express PD-L1 (≥ 1)
Month: December
To read more, visit: bit.ly/4fCl61n

Encorafenib (Braftovi) plus cetuximab and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin)

Approval type: Accelerated
Indication: Patients with metastatic CRC with a BRAF V600E mutation, as detected by an FDA-approved test
Month: December
To read more, visit: bit.ly/3DxAhvd

Erdafitinib (Balversa)

Approval type: Regular
Indication: Adult patients with locally advanced or metastatic urothelial carcinoma harboring susceptible FGFR3 alterations, as determined by an FDA-approved test, whose disease has progressed on or following at least 1 prior line of systemic therapy. The FDA noted that this approval amends the indication previously granted under accelerated approval for patients with metastatic urothelial carcinoma with susceptible FGFR3 or FGFR2 alterations following prior platinum-containing chemotherapy.
Month: January
To read more, visit: bit.ly/4fsSmI1

Nivolumab plus cisplatin and gemcitabine

Approval type: Regular
Indication: Frontline treatment of adult patients with unresectable or metastatic urothelial carcinoma
Month: March
To read more, visit: bit.ly/3VILJKF

Nogapendekin alfa inbakicept-pmln (Anktiva) plus BCG

Approval type: Regular
Indication: Adult patients with Bacillus Calmette-Guérin–unresponsive non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors
Month: April
To read more, visit: bit.ly/3VH2eHc

Reference

1. Advancing health through innovation: New drug therapy approvals 2024. FDA. Accessed February 4, 2025. bit.ly/3WKqf0s