GASTRIC CANCER

An FDA Oncologic Drugs Advisory Committee meeting resulted in continued approval for 4 of 6 indications that were discussed, although all 6 indications did not demonstrate clinical benefit in confirmatory studies. The meeting, held April 27-29, evaluated anti–PD-1/PD-L1 drugs that received accelerated approvals through the FDA’s accelerated approval program, a nearly 30-year-old initiative to expedite the approval process.

The treatment landscape for gastric cancer is evolving. The use of biomarkers and implementation of testing to improve outcome later on in the course of treatment are being more important.

The latest updates on gastric and esophageal cancers focus on greater use of biomarkers, next-generation sequencing (NGS), and immunotherapies.

The FDA has granted orphan drug designation to the first-in-class ruthenium-based small molecule, BOLD-100, for the treatment of patients with gastric cancer.

The FDA has granted accelerated approval to pembrolizumab plus trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of patients with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction cancer.

Here is a look back at the FDA happenings from the month of April 2021.

The FDA’s Oncologic Drugs Advisory Committee has voted 6 to 2 against the continued approval of pembrolizumab as indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 who experienced disease progression on or after 2 or more prior lines of therapy, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2-targeted therapy.

The FDA has approved nivolumab in combination with certain chemotherapies for the initial treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

For the treatment of patients with HER2-amplified gastric cancers in addition to those with HER2 moderate-, low-, and non-expressing disease, trastuzumab deruxtecan has shown to be an effective therapeutic option.

The FDA has granted an orphan drug designation to ARX788 for the treatment of patients with HER2-positive gastric cancer, according to a press release from developer Ambrx.

In an interview with Targeted Oncology, Markus Moehler, MD, PhD, reviewed the potentially practice-changing data from the phase 3 CheckMate 649 clinical trial.

In the phase 2 JACCRO GC-07 trial, patients with stage III gastric cancer who received the combination of S-1 and docetaxel in the adjuvant setting had a 29% reduction in the risk of relapse.

In the frontline setting of FGFR2b-positive advanced gastric or gastroesophageal junction adenocarcinoma, the combination of bemarituzumab combined with mFOLFOX6 achieved a 56% reduction in the risk of disease progression or death compared with placebo.

Dr Catenacci discusses the DESTINY-Gastric01 study, including personal experience using trastuzumab deruxtecan.

Dr Catenacci highlights clinical trials in HER2-positive gastric cancer that may provide insight on differences in mechanism of resistance from one tumor type to another.

Daniel Catenacci, MD, discusses treatment options after second-line therapy, highlighting options for patients who are PD-L1 positive.

Daniel Catenacci, MD, examines factors that help decide when to switch treatment from first to second line, and when to change mechanism of action in treating gastric carcinoma.

Daniel Catenacci, MD, discusses initial considerations for treatment in patients with microsatellite instability-high/stable, HER2-positive/negative gastric cancer and touches on second-line treatment options.

Dr Catenacci evaluates the case of a 71-year-old man with gastric cancer, and provides insight on molecular testing in gastric cancer and initial treatment options.

The FDA granted a Priority Review designation to the supplemental Biologics License Application for trastuzumab deruxtecan as treatment of patients with HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma.

In an interview with Targeted Oncology following a virtual presentation for the ISGIO 2020, Yelena Janjigian, MD, provided an overview of the role of HER2-targeted therapies in advanced gastric cancer. She also explained the importance of biomarker testing in this space.

The FDA has granted a Fast Track designation to DKN-01 for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express the protein DKK1, following disease progression on or after prior treatment with fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, human epidermal receptor growth factor/neu-targeted therapy.

In the phase 3 ATTRACTION-4 study, nivolumab added to chemotherapy led to a statistically significant improvement in progression-free survival and induced higher overall response rates in patients with previously untreated advanced or recurrent gastric and gastroesophageal junction cancer, according to results presented during the 2020 ESMO Virtual Congress.

Overall survival and progression-free survival were improved with nivolumab plus ipilimumab and chemotherapy compared with chemotherapy alone as frontline treatment of patients with metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

During a virtual Case Based Peer Perspectives series, Madappa Kundranda, MD, PhD, discussed the case of a 60-year-old male patient diagnosed with poorly differentiated gastric adenocarinoma.

The FDA has granted margetuximab an orphan drug designation for the treatment of patients with gastric and gastroesophageal junction cancer.

Data from 2 phase 2 trials involving fam-trastuzumab deruxtecan-nxki revealed the agent’s ability to induce responses in patients with HER2-positive metastatic colorectal cancer and advanced gastric or gastroesophageal junction adenocarcinoma.

Fam-trastuzumab deruxtecan-nxki has received an Orphan Drug designation for the treatment of patients with gastric or gastroesophageal junction cancer.

Shuichi Hironaka, MD, PhD, discusses the efficacy of a phase I/II study of nivolumab, paclitaxel, and ramucirumab as second-line treatment of patients with advanced gastric cancer during the 2020 Gastrointestinal Cancers Symposium.

The FDA has accepted and granted a priority review to a supplemental Biologics License Application for pembrolizumab for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high who have progressed following prior treatment and who have no satisfactory alternative treatment options.