A deflated lung-shaped balloon symbolizes disappointment in lung cancer research.

Denosumab and Lung Cancer: Is There a Link?

Rhea Morgan in Health & Wellness December 2025 • 4 min read.

"A new study questions the potential survival benefits of denosumab in advanced non-small cell lung cancer (NSCLC)."

Lung cancer remains a leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for the majority of these cases, often diagnosed at an advanced stage when treatment options are limited. Researchers are continuously exploring new therapies and treatment strategies to improve outcomes for patients with this devastating disease.

One area of interest has been the potential role of denosumab, a medication primarily used to treat osteoporosis and prevent skeletal-related events in patients with bone metastases. Previous studies hinted at a possible survival advantage for lung cancer patients treated with denosumab, sparking further investigation.

The SPLENDOUR trial, a randomized phase III study, aimed to definitively evaluate whether adding denosumab to standard first-line chemotherapy could improve overall survival in patients with advanced NSCLC. However, the results of this trial have cast doubt on the initial optimism, prompting a re-evaluation of denosumab's role in lung cancer treatment.

What is Denosumab and Why Was It Studied for Lung Cancer?

A deflated lung-shaped balloon symbolizes disappointment in lung cancer research.

Denosumab is a monoclonal antibody that targets RANKL (receptor activator of nuclear factor kappa-B ligand), a protein that plays a key role in bone remodeling. By blocking RANKL, denosumab inhibits bone resorption, making it effective in treating conditions like osteoporosis and preventing fractures.

The rationale for investigating denosumab in lung cancer stemmed from several observations:

RANKL's Role in Cancer: RANKL is not only involved in bone metabolism but also influences cell signaling pathways that can promote cancer growth and spread.
Bone Metastases: Lung cancer frequently metastasizes to the bone, causing pain, fractures, and other complications. Denosumab is already used to manage these skeletal-related events.
Previous Studies: Retrospective analyses of earlier trials suggested that denosumab might improve overall survival in lung cancer patients, warranting further investigation in a dedicated prospective study.

Given these factors, the SPLENDOUR trial was designed to rigorously assess the impact of denosumab on survival when combined with standard chemotherapy in patients with advanced NSCLC.

What Does This Mean for Lung Cancer Patients?

The SPLENDOUR trial's findings highlight the complexities of cancer treatment and the importance of rigorous clinical trials. While denosumab remains a valuable tool for managing bone metastases in lung cancer, it does not appear to offer a survival advantage when added to standard chemotherapy. Ongoing research continues to explore new avenues for improving outcomes in NSCLC, offering hope for more effective therapies in the future.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

What is Denosumab and what is its primary use?

Denosumab is a monoclonal antibody that targets RANKL (receptor activator of nuclear factor kappa-B ligand). Its primary use is to treat osteoporosis and prevent skeletal-related events like fractures, particularly in patients where cancer has spread to the bone (bone metastases). Denosumab achieves this by inhibiting bone resorption, a process where bone tissue is broken down.

Why was Denosumab initially considered as a potential treatment for lung cancer?

Denosumab was considered for lung cancer treatment due to several factors. First, RANKL, the target of Denosumab, plays a role in cell signaling pathways that can promote cancer growth and spread. Second, lung cancer often metastasizes to the bone, and Denosumab is already used to manage complications like bone metastases. Finally, some retrospective analyses of earlier trials suggested that Denosumab might improve overall survival in lung cancer patients, leading to the SPLENDOUR trial.

What was the purpose of the SPLENDOUR trial and what were its findings?

The SPLENDOUR trial was a randomized phase III study designed to evaluate whether adding Denosumab to standard first-line chemotherapy could improve overall survival in patients with advanced non-small cell lung cancer (NSCLC). The trial's findings were that adding Denosumab to standard chemotherapy did not offer a survival advantage for patients with advanced NSCLC. This means that while Denosumab remains useful for managing bone metastases, it does not appear to improve how long patients live when added to their chemotherapy.

How does the study of Denosumab in lung cancer highlight the complexities of cancer treatment?

The study of Denosumab in lung cancer exemplifies the complexities of cancer treatment because it shows that even though a drug may work in some ways (like managing bone metastases), it doesn't always translate into a direct survival benefit. The initial promise suggested by retrospective analyses did not hold up in a rigorous prospective clinical trial like SPLENDOUR. This underscores the need for careful investigation and the possibility that a drug's effects can be context-dependent.

In light of the SPLENDOUR trial results, what is the current role of Denosumab in treating non-small cell lung cancer (NSCLC)?

Based on the SPLENDOUR trial, the current role of Denosumab in treating non-small cell lung cancer (NSCLC) is primarily to manage skeletal-related events, such as bone metastases. While it is a valuable tool for addressing complications arising from the spread of cancer to the bone, the trial found no evidence that adding Denosumab to standard chemotherapy improves overall survival in patients with advanced NSCLC. Research continues to explore new therapies, but Denosumab's role, as supported by this evidence, is to manage the side effects in the bone, not necessarily to be an anticancer agent.