Treatment

Combination Therapy

Combination therapy, including adjuvant and neoadjuvant approaches, has become a cornerstone in lung cancer management, offering significant benefits before, during, and after primary treatment.

Delve into the world of adjuvant therapy

Dr. Jonathan Villena-Vargas, an assistant professor of cardiothoracic surgery, and Lisa Goldman, a long-term lung cancer survivor and advocate discuss the differences between neoadjuvant, adjuvant, and peri-adjuvant therapies, and how treatment decisions are made.

About

Combination Therapy for lung cancer treatment is one of the latest, most exciting advances in lung cancer research.

Studies of patients being treated with combination therapy show increase in the overall survival rate for lung cancer patients.

In the 1970s, researchers discovered that using a combination of drugs to treat a cancer patient increases the chance that all of the cancer cells will be eliminated. Preliminarily, clinical trials have shown that the combination of immunotherapy with other therapy, such as chemotherapy, radiotherapy, and targeted therapy, achieve greater therapeutic effects for treating small cell lung cancer (SCLC).

Some of the positive reasons doctors may choose to recommend combination therapy for certain lung cancer patients are:

  • A single treatment might not be sufficient to make the tumor shrink.
  • Sometimes adding an additional treatment may make the original treatment work better.
  • Certain treatments might be more effective at different stages of your treatment journey.

Understanding Combination Therapy

Combination therapy involves using multiple treatment modalities to combat lung cancer more effectively. This approach can include various combinations of:

  • Surgery
  • Radiation therapy
  • Chemotherapy
  • Immunotherapy
  • Targeted therapy

The goal is to attack cancer cells from different angles, potentially improving treatment outcomes and reducing the risk of recurrence.

Types of Treatment

Neoadjuvant therapy is administered before the primary treatment, usually surgery. This approach offers several benefits:

  • Improves surgical outcomes by shrinking tumors
  • Allows assessment of treatment efficacy
  • May reduce cancer spread
  • Potential for better prognosis
  • Provides more treatment options
  • Allows for personalized medicine based on tumor response

Adjuvant therapy is given after the primary treatment to target any remaining cancer cells. Key benefits include:

  • Reducing the risk of cancer recurrence
  • Prolonging survival rates
  • Allowing for personalized treatment approaches
  • Offering alternative options for non-surgical candidates

Recent advancements have led to the incorporation of immunotherapy and targeted therapy into combination treatment plans:

Immunotherapy: Drugs like pembrolizumab and atezolizumab are now used in combination with chemotherapy as first-line treatments for certain types of non-small cell lung cancer (NSCLC).

Targeted Therapy: For patients with specific genetic mutations, targeted therapies like osimertinib or alectinib may be combined with other treatments for improved outcomes.

Ongoing research continues to explore new combination approaches, including:

  • Triple combination therapies (e.g., chemotherapy + immunotherapy + targeted therapy)
  • Combining different immunotherapy drugs
  • Sequencing of various treatment modalities for optimal results

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What to Expect

The specific treatment plan for combination therapy will depend on the individual patient’s condition, including the type and stage of lung cancer. Here are some general aspects to expect during combination therapy:

  • Treatment Schedule: Combination therapy may involve receiving different treatments on different days or in specific cycles. The treatment schedule will be determined by the healthcare team and may vary for each patient.
  • Potential Side Effects: Like any cancer treatment, combination therapy can have side effects. These can vary depending on the specific treatments used. Common side effects may include fatigue, nausea, hair loss, and changes in blood cell counts. It is important to discuss potential side effects with the healthcare team and seek appropriate support and management strategies.
  • Monitoring and Follow-up: Regular monitoring and follow-up visits will be an essential part of combination therapy. This allows healthcare professionals to assess treatment response, manage side effects, and make any necessary adjustments to the treatment plan.

Side Effects

See side effects for each related therapy:

Chemotherapy

Immunotherapy

Targeted Therapy

FDA-Approved Combination Therapy Treatment

Types

  • Ipilimumab (Yervoy)

    Ipilimumab (Yervoy) is a special drug that helps fight lung cancer by the immune system attacking cancer cells. It’s used for NSCLC that has:

    • Spread to other parts of the body
    • A protein called PD-L1
    • No changes in genes called EGFR or ALK

     

    Ipilimumab can be used:

    • As a first treatment for some patients
    • With other cancer drugs called chemotherapy
    • Before surgery (neo-adjuvant) for early-stage NSCLC

    Approved for: NSCLC

    Biomarkers: PD-L1

    FDA Approval Date: 05/26/2020

    Used in: Adjuvant Therapy, Combination Therapy, Targeted Therapy

  • Tremelimumab (Imjudo)

    FDA approved tremelimumab in combination with durvalumab and platinum-based chemotherapy for adult patients with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

    Approved for: NSCLC

    FDA Approval Date: 11/01/2022

    Used in: Combination Therapy

  • Cemiplimab-rwlc (Libtayo)

    FDA approved cemiplimab-rwlc in combination with platinum-based chemotherapy for adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK, or ROS1 aberrations.

    Approved for: NSCLC

    FDA Approval Date: 11/01/2022

    Used in: Combination Therapy

  • Pembrolizumab (Keytruda)

    FDA approved pembrolizumab for adjuvant treatment following resection and platinum-based chemotherapy for stage 1B (T2a ≥4 cm), 2, or 3A non-small cell lung cancer (NSCLC).

    Approved for: NSCLC

    FDA Approval Date: 01/01/2023

    Used in: Combination Therapy

  • Encorafenib (Braftovi)

    The FDA has approved encorafenib plus binimetinib for adult patients with metastatic non–small cell lung cancer harboring a BRAF V600E mutation.

    Approved for: NSCLC

    Biomarkers: BRAF

    FDA Approval Date: 10/11/2023

    Used in: Combination Therapy

  • Nivolumab (Opdivo/Opdivo Injection)

    FDA-approved nivolumab with platinum-doublet chemotherapy for adult patients with resectable non-small cell lung cancer (NSCLC) in the neoadjuvant setting.

    Approved for: NSCLC

    FDA Approval Date: 03/01/2022

    Used in: Adjuvant Therapy, Combination Therapy, Immunotherapy

  • Atezolizumab (Tecentriq)

    Non-small cell lung cancer that has metastasized. It is used:

    As first-line therapy in adults whose cancer has the PD-L1 protein and does not have a mutation in the EGFR gene or the ALK gene.

    In adults whose cancer has gotten worse during or after treatment with platinum chemotherapy.

    For patients whose cancer has a mutation in the EGFR gene or ALK gene, atezolizumab is used if their disease has gotten worse after treatment with FDA-approved therapy for these mutations.

    Approved for: NSCLC

    Biomarkers: PD-L1

    FDA Approval Date: 10/31/2023

    Used in: Combination Therapy, Targeted Therapy

  • Durvalumab (Imfinzi)

    Small cell lung cancer in adults. It is used with etoposide phosphate and either carboplatin or cisplatin as first-line therapy in adults with extensive-stage disease.

    Approved for: SCLC

    FDA Approval Date: 12/21/2024

    Used in: Combination Therapy

  • Nivolumab (Opdivo/Opdivo Injection)

    Nivolumab, alone or with Ipilimumab, is an
FDA-approved immunotherapy option or combination to treat many types of non-small cell lung cancer (NSCLC).

    It is used:

    • As first-line therapy with ipilimumab in adults whose cancer is metastatic and has the PD-L1 protein but does not have mutations in the EGFR or ALK gene.
    • As first-line therapy with ipilimumab and platinum chemotherapy in adults whose cancer is metastatic or recurrent but does not have mutations in the EGFR or ALK gene.
    • In patients whose cancer is metastatic and has gotten worse during or after treatment with platinum chemotherapy. Patients whose cancer has a mutation in the EGFR or ALK gene should receive nivolumab only if their disease got worse after treatment with FDA-approved therapy for these gene mutations.

    Approved for: NSCLC

    Biomarkers: PD-L1

    FDA Approval Date: 09/27/2024

    Used in: Adjuvant Therapy, Combination Therapy, Targeted Therapy

  • Methotrexate Sodium (Trexall/Xatmep)

    Methotrexate has been a key player in cancer treatment for decades, particularly for lung cancer. It works by inhibiting the enzyme dihydrofolate reductase, which is essential for DNA synthesis and cell division, effectively slowing or stopping the growth of cancer cells. Often used in combination with other drugs, methotrexate is especially beneficial in advanced stages of lung cancer and can serve as an option for cases resistant to other treatments. First approved by the FDA in 1953, its long-standing track record has provided a solid understanding of its effects over more than 70 years.

    Approved for: NSCLC, SCLC

    FDA Approval Date: 01/01/1953

    Used in: Adjuvant Therapy, Chemotherapy, Combination Therapy, SCLC

  • Cisplatin

    Cisplatin is a chemotherapy drug, targeting the DNA of cancer cells to hinder their replication and ultimately induce cell death. It is effective against both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Often used in combination with other agents to enhance efficacy, cisplatin serves as a first-line treatment for advanced NSCLC and is also utilized in SCLC for both first-line and second-line therapies. Additionally, it can be administered after surgery to eliminate remaining cancer cells or before surgery to shrink tumors, making procedures more effective. Cisplatin was first approved by the FDA in 1978 and became a standard treatment for lung cancer through clinical studies in the 1980s and 1990s, boasting a proven track record of over 40 years in cancer therapy.

    Approved for: NSCLC, SCLC

    FDA Approval Date: 01/01/1978

    Used in: Chemotherapy, Combination Therapy

  • Carboplatin (Paraplatin)

    Carboplatin, also known as Paraplatin, is a chemotherapy drug used in the treatment of lung cancer, effective against both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). It disrupts the DNA replication in cancer cells, leading to their death. It can be employed as part of combination chemotherapy to enhance effectiveness, used after surgery to eliminate residual cancer cells, or given before surgery to shrink tumors for improved surgical outcomes. Additionally, carboplatin plays a role in palliative care for advanced lung cancer. First approved by the FDA in 1989, it has a proven track record in clinical practice over the past three decades.

    Approved for: NSCLC, SCLC

    Biomarkers: SCLC

    FDA Approval Date: 01/01/1989

    Used in: Adjuvant Therapy, Combination Therapy, SCLC

  • Gemcitabine Hydrochloride (Gemzar/Infugem)

    Gemcitabine hydrochloride, marketed under names like Gemzar and Infugem, is a chemotherapy drug used to treat non-small cell lung cancer (NSCLC). First approved by the FDA in 1998, it works by interfering with DNA synthesis in cancer cells, helping to slow down or stop their growth. Gemcitabine is often used in combination with other chemotherapy agents to enhance its effectiveness and can be employed in advanced stages of cancer or in cases where surgery isn’t an option. It is used with cisplatin.

    Approved for: NSCLC

    FDA Approval Date: 08/01/1998

    Used in: Chemotherapy, Combination Therapy

  • Docetaxel (Taxotere)

    Docetaxel, marketed as Taxotere, is a chemotherapy drug used in the treatment of lung cancer, specifically non-small cell lung cancer (NSCLC). First approved by the FDA for NSCLC in 1999, docetaxel works by disrupting the normal function of microtubules, which are essential for cell division, ultimately leading to cancer cell death. It is commonly used as a first-line treatment in combination with other agents, such as cisplatin, for advanced NSCLC, and can also be an effective option for patients whose cancer has progressed after initial treatments. Additionally, docetaxel is utilized in the second-line setting for NSCLC patients who have not achieved the desired response with prior therapies, offering a valuable alternative in their treatment plan.

    Approved for: NSCLC

    FDA Approval Date: 01/01/1999

    Used in: Chemotherapy, Combination Therapy, Immunotherapy, Targeted Therapy

  • Erlotinib (Tarceva)

    Erlotinib, marketed as Tarceva, is a targeted therapy primarily used to treat non-small cell lung cancer (NSCLC), particularly in patients with specific genetic mutations. The FDA first approved erlotinib in 2004 for the treatment of advanced NSCLC in patients who had previously received at least one chemotherapy regimen. Erlotinib works by inhibiting the epidermal growth factor receptor (EGFR), which is often mutated in NSCLC, leading to reduced tumor growth and improved patient outcomes. It is commonly used as a first-line treatment for patients with EGFR-mutant NSCLC and can also be an effective second-line option for those whose disease has progressed after chemotherapy. Additionally, erlotinib is sometimes used in combination with other therapies, such as chemotherapy or targeted treatments, enhancing its effectiveness in managing advanced lung cancer. Its targeted approach emphasizes the importance of genetic testing in personalizing lung cancer treatment strategies.

    Approved for: NSCLC

    Biomarkers: EGFR

    FDA Approval Date: 01/17/2024

    Used in: Combination Therapy, Targeted Therapy

  • Bevacizumab (Avastin/Mvasi/Zirabev)

    Bevacizumab, marketed under names such as Avastin, Mvasi, and Zirabev, is a monoclonal antibody used in the treatment of non-small cell lung cancer (NSCLC). The FDA first approved bevacizumab in 2006 specifically for use in combination with chemotherapy for patients with advanced NSCLC. It works by inhibiting vascular endothelial growth factor (VEGF), which is crucial for tumor blood vessel formation. By blocking VEGF, bevacizumab helps to starve tumors of the nutrients they need to grow. In lung cancer treatment, bevacizumab is typically used in combination with carboplatin and paclitaxel or other chemotherapy regimens, making it a valuable option for patients with advanced disease.

    Approved for: NSCLC

    FDA Approval Date: 01/01/2006

    Used in: Chemotherapy, Combination Therapy, Targeted Therapy

  • Dabrafenib (Tafinlar)

    Non-small cell lung cancer that has metastasized. It is used with trametinib.Dabrafenib is used only in patients whose cancer has a certain mutation in the BRAF gene.

    Approved for: NSCLC

    Biomarkers: BRAF

    FDA Approval Date: 12/21/2024

    Used in: Combination Therapy, Targeted Therapy

  • Trametinib (Mekinist)

    Non-small cell lung cancer that has metastasized. It is used with dabrafenib.
    Trametinib is used only in patients whose cancer has a certain mutation in the BRAF gene.

    Approved for: NSCLC

    Biomarkers: BRAF

    FDA Approval Date: 12/21/2024

    Used in: Combination Therapy, Targeted Therapy