FDA Amends Keytruda Approval for Gastric, GEJ Cancer

The Food and Drug Administration (FDA) revised the approval indication of Keytruda (pembrolizumab) plus Enhertu (trastuzumab), fluropyrimidine and platinum-based chemotherapy for the frontline treatment of locally advanced unresectable (not able to be surgically removed) or metastatic (spread to different parts of the body) HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Now, the agency is stating that the indication — which was granted an accelerated approval — is only for patients whose tumors express the PD-L1 protein, according to a recent statement from the agency.

Additionally, the FDA approved the Agilent PD-L1 IHC 22C3 pharmDx as a companion diagnostic to determine patients with gastric or GEJ adenocarcinoma have PD-L1.

Keytruda works by binding to the PD-1 receptor, thereby blocking interactions with PD-L1 and PD-L2 proteins found on cancer cell surfaces. PD-L1/PD-L2 helps tumors hide from the immune system, so inhibiting them allows for T cells to find and fight the cancer.

This Keytruda-containing regimen — which was initially for patients regardless of their PD-L1 status — was granted an accelerated approval in May 2021 based on findings from the ongoing KEYNOTE-811 clinical trial. Then, updated findings from the trial, which were presented at the 2023 European Society of Medical Oncology Congress showed that the immunotherapy-based treatment protocol was particularly beneficial for patients with a PD-L1 combined positive score (CPS) of 1 or more.

READ MORE:Keytruda Plus Herceptin, Chemo Boosts PFS in HER2+ Gastric/GEJ Cancer

Findings from a median follow-up of approximately 38 months showed that progression-free survival (time from treatment until disease worsening or death) was 10 months for patients treated with the Keytruda combination, compared with 8.1 months for patients given placebo plus Enhertu (trastuzumab), fluropyrimidine and platinum-based chemotherapy. For patients with PD-L1—positive cancers, the progression-free survival was even better for those who received Keytruda, at 10.9 months, compared with 7.3 months for those given a placebo.

Median overall survival (time from treatment until death of any cause) was also better in patients who received the Keytruda-containing regimen. For both the overall population and those whose tumors expressed PD-L1, the median overall survival was 20 months for the Keytruda combination. Those who received the placebo-containing therapy had a median overall survival of 16.8 months and 15.7 months in the PD-L1—negative and —positive groups, respectively.

The safety profile of Keytruda, Herceptin and chemotherapy observed in the KEYNOTE-811 trial was consistent of that was previously observed with the drugs, either alone or in combination with one another. Since Keytruda works by igniting the patient’s immune system, patients may experience immune-related side effects, such as inflammation, that can affect any organ system.

READ MORE:Immunotherapy Side Effects: ‘No Organ System Potentially Unaffected’

Serious side effects related to Keytruda or the Agilent PD-L1 IHC 22C3 pharmDx companion diagnostic should be reported to the FDA’s MedWatch Reporting System.

According to the FDA, the recommended dose for Keytruda is 200 mg every three weeks or 400 mg every six weeks until the disease worsens, unacceptable side effects or up to 24 months. When Keytruda, Herceptin and chemotherapy are all administered on the same day, Keytruda should be given first.

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