Differences in efficacy and indications between durvalumab (durvalumab) and pembrolizumab

Durvalumab (Durvalumab) and Pembrolizumab (Pembrolizumab) are both immune checkpoint inhibitors used in the treatment of a variety of solid tumors. The basic mechanism of both involves the release of tumor suppression of the immune system, but there are significant differences in their targets and clinical applications. Understanding these differences can help select the most appropriate immunotherapy drug for a specific cancer type and stage of treatment, as well as evaluate efficacy and safety.

First of all, the mechanisms of action are different. Pembrolizumab targets the programmed death receptor1 (PD‑1) monoclonal antibody, by blockingPD‑1 and its ligand PD‑L1 and PD‑L2 relieves the inhibition of T cells and restores the ability of T cells to attack tumor cells. Durvalumab targets PD‑L1 by binding to PD‑L1Blocking its interaction with PD‑1 and with CD80 also achieves the effect of activating anti-tumor immunity. This difference in targets means that there may be different immune activation patterns in different tumor microenvironments. In general, PD‑1 inhibitors (such as pembrolizumab) directly block the receptor, whereas PD‑L1 inhibitors (such as durvalumab) block the ligand, which in some cases may make PD pan>‑1 inhibitors also block ‑L2-mediated inhibition, whereas PD‑L1 inhibitors do not necessarily affect this pathway.

Secondly, there are differences in indications between the two. Pembrolizumab is currently approved for use in a variety of tumor types, including but not limited to locally advanced or metastatic non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, gastroesophageal junction or esophageal cancer, urothelial cancer, melanoma, and a variety of other solid tumors, and can be used as a first-line treatment option as a single agent or in combination with chemotherapy. These indications are often based on the results of multiple large-scale Phase III clinical trials, such as the KEYNOTE series of studies, which show that combination chemotherapy can significantly improve overall survival (OS) and progression-free survival (PFS). In contrast, durvalumab's approved indications are relatively concentrated, and are traditionally used in combination with chemotherapy for locally advanced or metastatic cholangiocarcinoma, inoperable limited-stage stage III non-small cell lung cancer as maintenance treatment after chemoradiotherapy, and certain urothelial cancers. Most of these indications are based on clinical benefit demonstrated during a specific phase of treatment (such as maintenance after chemoradiotherapy).

In terms of efficacy, network meta-analysis suggested that in indirect comparisons of overall survival and progression-free survival, pembrolizumab and durvalumab did not show significant differences in most solid tumors, suggesting that PD as a class ‑1/PD‑L1 inhibitors, their overall efficacy may be similar. This conclusion is based on indirect comparisons of different tumor types and clinical settings rather than direct head-to-head controlled trials. However, in some specific cases, the efficacy of the two may differ due to factors such as tumor biology, patient's PD‑L1 expression level, combination drug strategy, etc. This needs to be determined based on specific clinical trial data.

In terms of safety, both types of drugs can cause immune-related adverse events (irAEs), including pneumonia, hepatitis, enteritis, endocrine dysfunction, etc. These are side effects caused by excessive activation of the immune system. Although the specific incidence and types vary in different studies, in general, there is no significant difference in the risk of serious adverse reactions between PD‑1 and PD‑L1 inhibitors, both of which require close monitoring and timely treatment.

In terms of clinical use strategy, pembrolizumab is more widely used in first-line treatment due to its wider indications and more single-agent or combination regimens. For example, it can be used as a single-agent first-line treatment in patients with high PD‑L1 expression of NSCLC. Durvalumab plays an important role in certain specific stages of treatment, such as maintenance treatment after chemotherapy or radiochemotherapy. In addition, research on combining the two with other immune or targeted drugs is also ongoing, aiming to further improve efficacy or overcome drug resistance.

In general, although pembrolizumab and durvalumab are both immune checkpoint inhibitors, they have substantial differences in their targets, indication spectrum, and clinical application scenarios. The specific choice of drug should be comprehensively evaluated based on tumor type, patient characteristics, PD‑L1 expression status, and existing clinical evidence.

Keyword tags:

Durvalumab, pembrolizumab, PD-L1 inhibitors, PD-1 inhibitors, immune checkpoint inhibitors, differences in indications, comparison of efficacy, irAEs

Reference materials:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797652/