This therapy combines two chemotherapy drugs, carboplatin and pemetrexed, with the immunotherapy drug pembrolizumab. It is a first-line treatment for metastatic non-squamous non-small cell lung cancer (NSCLC) that lacks specific genomic changes in the EGFR or ALK genes. The goal is to shrink tumors and reduce symptoms by pairing chemotherapy’s cell-killing action with immunotherapy’s immune-stimulating effects.
How This Combination Therapy Works
The chemotherapy agents, carboplatin and pemetrexed, function by targeting cells that divide rapidly. Carboplatin is a platinum-based compound that damages the DNA within cancer cells. This damage creates cross-links in the DNA strands, which interferes with the cell’s ability to repair its genetic material and replicate, leading to cell death.
Pemetrexed, known by the brand name Alimta, is an antifolate agent. It operates by blocking several enzymes that are necessary for the synthesis of DNA and RNA. By inhibiting these metabolic pathways, pemetrexed starves cancer cells of the materials they need to grow and multiply.
Pembrolizumab, sold under the brand name Keytruda, is a type of immunotherapy known as a PD-1 inhibitor. Some cancer cells protect themselves by expressing a protein called PD-L1, which binds to the PD-1 receptor on T-cells. This binding acts as a “don’t attack me” signal, hiding the cancer from immune surveillance.
Pembrolizumab blocks the PD-1 receptor, preventing the cancer cells’ PD-L1 from binding to it. This action removes the “brakes” from the T-cells, allowing them to recognize and attack the cancer cells. When chemotherapy drugs kill cancer cells, the dying cells can release antigens, which can help the newly activated immune cells more effectively identify their targets.
The Treatment Process
This therapy is administered intravenously (IV) in a hospital or specialized cancer clinic. The treatment is delivered in cycles, with one cycle occurring every three weeks. This schedule allows the body time to recover between doses.
Before the main infusions begin, patients receive pre-medications to prevent or lessen side effects. These often include a corticosteroid like dexamethasone to reduce infusion reactions and anti-nausea medications to manage a common chemotherapy side effect.
Patients receiving pemetrexed must also take folic acid supplements and receive vitamin B12 injections. These supplements are started before the first dose and continue throughout treatment. They help protect healthy cells and reduce the severity of certain side effects, particularly low blood counts and mouth sores.
The initial phase involves up to four cycles of the full three-drug combination. If imaging scans show the cancer is stable or has responded well, the plan may be adjusted. Patients often move to a maintenance therapy phase, which involves continuing treatment with just pembrolizumab and pemetrexed to maintain control over the disease.
Potential Side Effects
Patients may experience side effects from both the chemotherapy and immunotherapy components. The chemotherapy drugs, carboplatin and pemetrexed, are often associated with fatigue, nausea, vomiting, a decrease in appetite, and mouth sores. Some individuals may also notice hair thinning, although complete hair loss is less common than with other chemotherapy regimens.
A primary effect of chemotherapy is its impact on the bone marrow, leading to a condition known as myelosuppression, or lowered blood cell counts. A reduction in white blood cells increases the risk of infections. Lowered red blood cell counts (anemia) can cause or worsen fatigue and shortness of breath, while a drop in platelet levels increases the risk of bruising and bleeding.
The immunotherapy drug, pembrolizumab, activates the immune system, which can sometimes cause it to mistakenly attack healthy tissues and lead to inflammation. Skin reactions, such as rash and itching, are common. Inflammation in the colon (colitis) can cause diarrhea, while inflammation in the lungs (pneumonitis) may lead to coughing or shortness of breath.
Other organs can also be affected, including the liver (hepatitis) or hormone-producing glands like the thyroid. It is important for patients to report any new or worsening symptoms to their medical team immediately. This includes signs of infection like a fever, severe diarrhea, difficulty breathing, or a blistering skin rash.
Monitoring and Assessing Treatment Efficacy
The main tool for assessing the cancer’s response is medical imaging. Before treatment begins, a baseline CT or PET scan is performed to measure the size and extent of the tumors. These scans are then repeated at regular intervals, typically every six to nine weeks.
These follow-up scans allow the oncologist to compare new images to the baseline scans. This comparison reveals whether tumors are shrinking (a response), remaining the same size (stable disease), or growing (progressive disease).
Regular blood tests are conducted throughout the treatment course. These tests monitor for the side effects of treatment, such as changes in blood cell counts. In some cases, blood tests may also track levels of specific tumor markers, which are substances that can correlate with the amount of cancer in the body.
The oncologist’s clinical assessment is also a part of the monitoring process. During appointments, the doctor will evaluate the patient’s overall health, discuss any symptoms, and assess their ability to tolerate the treatment. This evaluation, combined with scans and blood work, provides a comprehensive picture of the treatment’s efficacy.