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FDA Expands Use of Keytruda for Treatment of NSCLC (TPS ≥ 1%)

This past week, the US FDA (the United States Food and Drug Administration) expanded the use of the cancer immunotherapy drug Keytruda (pembrolizumab). Keytruda is indicated for use by individuals with several different types of cancer, including skin cancer, Hodgkin lymphoma, gastric cancer, cervical cancer, and bladder cancer, among others. After this recent expansion, Keytruda will now be intended for use as a first-line treatment for individuals with stage III or metastatic non-small cell lung cancer, with a PD-L1 TPS ≥ 1%, who are not candidates for definitive chemoradiation or surgical resection. Additionally, these individuals must have cancer cells that do not express certain mutations, including EGFR or ALK mutations.

PD-L1 and Keytruda

Previously, Keytruda, which is made by Merck Inc., was indicated for individuals with non-small cell lung cancer (NSCLC) who had a PD-L1 TPS (Tumor Proportion Score) of 50% or greater. An individual’s PD-L1 Tumor Proportion Score indicates how many of their cancer cells express PD-L1. An individual’s TPS must be determined using an FDA-approved test before treatment with Keytruda can be started.

When tumor cells express or have PD-L1, they may be able to use it to avoid our naturally occurring cancer fighting immune cells in the body. Immunotherapy medications that focus on PD-L1, like Keytruda, aim to block cancer’s ability to use PD-L1 to avoid our body’s naturally cancer killing immune system. Keytruda helps certain immune cells, called T-cells, stay active against cancer cells that may try to suppress them. This may prevent the growth and development of tumor cells within the body. However, it’s possible that these active T-cells can attack other, normal tissues within the body, which may lead to several of Keytruda’s side effects.

What does the research say?

The expansion of Keytruda comes after the KEYNOTE-042 clinical trial which was a randomized, multicenter, active-controlled trial looking at the efficacy of Keytruda against common chemotherapy treatments for individuals with varying PD-L1 TPS characteristics. Over 1,250 individuals with stage III or IV NSCLC with a PD-L1 TPS ≥ 1% were randomized to receive either an IV infusion of Keytruda once every three weeks or a common chemotherapy, including pemetrexed or paclitaxel. About half of the participants received Keytruda and the other half received chemotherapy. All individuals had not previously used any other systemic treatment options for their NSCLC. The study aimed to measure any differences in overall survival between those taking Keytruda and those taking chemotherapy.

The researchers separated the study participants into three groups based on their PD-L1 TPS numbers. The groups included individuals with PD-L1 TPS ≥ 50%, PD-L1 TPS ≥ 20%, and PD-L1 ≥ 1%. In each of the three groups, overall survival was improved for those taking Keytruda. Specifically, in the TPS ≥ 1% group, overall survival was 16.7 months on Keytruda versus 12.1 months on chemotherapy. For the TPS ≥ 20% group, overall survival was 17.7 months on Keytruda versus 13.0 months on chemotherapy. Finally, for the TPS ≥ 50% group, overall survival was 20 months on Keytruda versus 12.2 months on chemotherapy. Overall, these results suggest that even though those with the highest TPS may see the most benefit on Keytruda, there may also be a benefit for individuals with a PD-L1 TPS as low as 1%, which is why the medications use was expanded.

Common side effects

The most common side effects of Keytruda were fatigue, constipation, diarrhea, shortness of breath, decreased appetite, nausea, pneumonia, fever, weight loss, hypothyroidism, and rash. The recommended dose of Keytruda for NSCLC is an intravenous infusion of 200mg over 30 minutes every three weeks.1,2

  1. FDA expands pembrolizumab indication for first-line treatment of NSCLC (TPS ≥ 1%). US Food and Drug Administration. Published April 11, 2019. Accessed April 13, 2019.
  2. Keytruda Prescribing Information. US Food and Drug Administration. Published April 2019. Accessed April 13, 2019.