Pembrolizumab has emerged as a significant advancement in the treatment of lung cancer, representing a modern approach within immunotherapy. This medication works by harnessing the body’s own immune system, specifically its T-cells, to identify and combat cancer cells. As an immunotherapy, it aims to restore the natural defenses that cancer may have suppressed, offering a new avenue for patients facing this complex disease.
Understanding Pembrolizumab’s Action
Pembrolizumab, known by its brand name Keytruda, functions as an immune checkpoint inhibitor. Cancer cells can sometimes evade detection by the immune system through a specific pathway involving the PD-1 (Programmed Death-1) receptor on T-cells and its ligands, PD-L1 and PD-L2, often found on tumor cells. Normally, the binding of PD-L1 or PD-L2 to the PD-1 receptor sends an inhibitory signal to T-cells, preventing them from attacking healthy cells. Tumor cells exploit this mechanism by overexpressing PD-L1, effectively “turning off” the T-cells that would otherwise target them.
Pembrolizumab is a monoclonal antibody designed to bind specifically to the PD-1 receptor on T-cells. By attaching to PD-1, the drug blocks its interaction with PD-L1 and PD-L2, thereby lifting the “brakes” on the T-cells. This blockade re-energizes these T-cells, allowing them to recognize and attack cancer cells, leading to a sustained immune response.
Lung Cancer Types Treated with Pembrolizumab
Pembrolizumab is widely used in treating non-small cell lung cancer (NSCLC) across various stages, including metastatic disease and certain earlier stages. For patients with metastatic NSCLC, it can be a first-line treatment, either as a single agent or in combination with chemotherapy, particularly if their tumors express programmed death ligand 1 (PD-L1). The level of PD-L1 expression, often measured by a tumor proportion score (TPS), guides treatment decisions; for instance, a TPS of 1% or greater is a common threshold for eligibility in some settings. Patients with stage III NSCLC who are not candidates for surgery or definitive chemoradiation may also receive pembrolizumab as a first-line treatment if their tumors express PD-L1 at a TPS of 1% or higher, provided they do not have specific genetic changes.
The presence of certain genetic alterations, such as epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, influences the treatment sequence. If a patient has these mutations, they typically receive FDA-approved targeted therapies for these aberrations first. Pembrolizumab may then be considered if the disease progresses after these initial targeted treatments.
Pembrolizumab is also approved for the adjuvant treatment of NSCLC in patients who have undergone surgical resection and platinum-based chemotherapy. This post-surgery use is for those with stage IB, II, or IIIA NSCLC whose tumors express PD-L1 (TPS ≥1%). While primarily known for its role in NSCLC, pembrolizumab is also indicated for extensive-stage small cell lung cancer (SCLC) in combination with chemotherapy as a first-line treatment.
Administering Pembrolizumab and Managing Side Effects
Pembrolizumab is administered intravenously. The typical frequency for administration is every three weeks or every six weeks, depending on the specific treatment plan and patient needs. The duration of treatment can vary, often continuing for up to two years or until the disease progresses or unacceptable toxicity occurs. Each infusion session usually takes about 30 minutes.
Patients receiving pembrolizumab may experience side effects, many of which are immune-mediated adverse events (imAEs), occurring when the reactivated immune system attacks healthy tissues. Common imAEs can include fatigue, skin rashes, and inflammation of the colon (colitis), which may cause diarrhea. Other potential side effects involve the endocrine glands, leading to thyroid issues, or inflammation of the lungs (pneumonitis), which can cause shortness of breath or cough.
Prompt reporting of any new or worsening symptoms to healthcare providers is important for effective management. Depending on the severity of the immune-mediated side effect, treatment may involve temporary interruption or permanent discontinuation of pembrolizumab. Management often includes the use of corticosteroids, such as prednisone, to suppress the overactive immune response and reduce inflammation. Close monitoring by the healthcare team helps to identify and address these side effects early.
Treatment Results and Follow-Up
Patients receiving pembrolizumab for lung cancer can experience varied treatment outcomes, often measured by concepts such as response rates, progression-free survival, and overall survival. Response rates refer to the percentage of patients whose tumors shrink or disappear in response to treatment. Progression-free survival indicates the length of time a patient lives without their cancer getting worse, while overall survival measures the total length of time a patient lives after starting treatment. These measures are often compared to traditional chemotherapy in clinical trials.
Responses to pembrolizumab can be durable, meaning some patients experience long-lasting effects, including extended periods of remission. While not all patients achieve complete remission, long-term disease control is possible. Individual results can differ based on factors such as the specific type and stage of lung cancer, the presence of certain biomarkers like PD-L1 expression, and overall patient health.
Following the completion of pembrolizumab treatment, or during ongoing therapy, regular monitoring is an important aspect of patient care. This typically involves scheduled imaging scans, such as CT scans, to assess the status of the cancer and detect any signs of recurrence or progression. Additionally, healthcare providers will continue to conduct symptom checks and blood tests to monitor for any late-onset side effects or changes in overall health. This ongoing follow-up helps ensure that any potential issues are identified and addressed promptly.