When treating lung cancer, clinicians often consider several factors when deciding on a treatment plan, such as patients’ age, overall health and medical history, and the type and stage of lung cancer. Clinicians will also consider patients’ preferences via shared decision making with the clinician to determine the optimal approach. Tailored to patient need, treatment may include surgery, chemotherapy, immunotherapy or other pharmacologic agents, radiation therapy, or a combination of treatments.

Treatment for non–small cell lung cancer (NSCLC) typically involves an assessment of eligibility for surgery followed by choice of surgery, chemotherapy, radiation therapy, or a combination of treatments tailored to patient need as appropriate, depending on tumor type and stage.

According to the National Institutes of Health’s National Cancer Institute (NIH NIC), for NSCLC, results of standard treatment are poor except for the most localized cancers. The NIH also indicates that all newly diagnosed patients with NSCLC are potential candidates for studies evaluating new forms of treatment.

The NIH NIC recommendations for treatment of NSCLC can be found here.

The NIH NIC indicates that treatment options also under clinical evaluation include the following: combining local treatment (surgery); regional treatment (radiation therapy); systemic treatments (chemotherapy, immunotherapy, and targeted agents); and developing more effective systemic therapy.

Treatment of NSCLC is centered on precision medicine, and molecular analysis is performed on adenocarcinomas to detect specific mutations that can direct therapy. This field is swiftly advancing, and additional drugs are being evaluated. Additionally, several immuno-oncology drugs (nivolumab, pembrolizumab, durvalumab, and atezolizumab) are available for NSCLC treatment. These drugs stimulate immune responsiveness, assist in the cancer’s being recognized as foreign, and prevent the tumor’s ability to block the natural immune system response. These agents are often prescribed if the tumor advances despite chemotherapy (most often platinum-based doublets), and extensive research is being conducted to determine which tumors will respond to this treatment.

Remarkable developments and advancements have been made with regard to the treatment of lung cancer. For example, in October 2021, the FDA approved Tecentriq (atezolizumab), a monoclonal antibody designed to bind with programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), as the first and only immunotherapy for treatment of NSCLC in the adjuvant setting following surgery and platinum-based chemotherapy for adults with stage II-IIIA NSCLC whose tumors express PD-L1 ≥1%, as determined by an FDA-approved test.

Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech, stated, “Tecentriq is now the first and only cancer immunotherapy available for adjuvant treatment of NSCLC, introducing a new era where people diagnosed with early lung cancer may have the opportunity to receive immunotherapy to increase their chances for cure. The landmark approval gives physicians and patients a new way to treat early lung cancer that has the potential to significantly reduce risk of cancer recurrence, after more than a decade with limited treatment advances in this setting.”

Treatment options for recurrent lung cancer may differ by location and include repeat chemotherapy or targeted drugs for metastases, radiation therapy for local recurrence or pain caused by metastases, and brachytherapy for endobronchial disease when additional external radiation cannot be tolerated. Surgical resection of a solitary metastasis or for palliative purposes is considered rarely.

The treatment of a locally recurrent NSCLC follows the same guidelines as for primary tumor stages I to III. If surgery was employed initially, radiation therapy is the primary modality, and if the recurrence manifests as distant metastases, patients are treated as if they have stage IV disease, with a focus on palliation.

Treatment for recurrent or metastatic stage IV NSCLC includes chemotherapy or targeted drugs, and the choice depends on tumor histology, mutational profile, patient functional status, and patient preference.

Small cell lung cancer (SCLC) at any stage is, on average, initially responsive to treatment, but unfortunately responses are mostly short-lived. Chemotherapy, with or without radiation therapy, is offered depending on the stage of disease. In many patients, chemotherapy prolongs survival and improves quality of life enough to warrant its use. Surgery generally plays no role in treatment of SCLC, although it may be curative in the rare patient with a small focal tumor without spread (such as a solitary pulmonary nodule) who underwent surgical resection before the tumor was identified as SCLC. The NIH NIC notes that with integration of current chemotherapy regimens into the treatment program, however, survival is prolonged, with at least a fourfold to fivefold improvement in average survival compared with patients who are given no therapy.

Chemotherapy regimens of etoposide and a platinum compound (either cisplatin or carboplatin) are the most frequently utilized standard regimen, as are other drugs, such as irinotecan, topotecan, vinca alkaloids (vinblastine, vincristine, vinorelbine), alkylating agents (cyclophosphamide, ifosfamide), doxorubicin, taxanes (docetaxel, paclitaxel), and gemcitabine.

The NIH NIC indicates that chemotherapy and radiation therapy have been demonstrated to improve survival for patients with SCLC. The NIH NIC recommendations for treatment of SCLC can be found here.

The NIH NIC also notes that despite treatment advances, the majority of patients with SCLC have a poor prognosis, even with the best available therapy, although patients who retain a good performance status should be offered further treatment in a clinical trial when feasible. The NIH NIC also notes that the majority of improvements in the survival of patients with SCLC are due to clinical trials that have endeavored to expand and enhance therapies.

Recent Lung Cancer Treatment News

• On November 8, 2022, the FDA approved the programmed death-receptor 1 (PD-1)  inhibitor cemiplimab-rwlc in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced non–small cell lung cancer (NSCLC)  with no epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase or c-ROS oncogene aberrations. Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation. Patients may be treated with this combination irrespective of PD-L1 expression or histology.

• New data published in Nature Medicine show that the immuno-oncology drug Tecentriq (atezolizumab) may be a safe and effective treatment for patients with stage IB to IIIB NSCLC prior to surgery.

• Researchers recently noted that data from the POSEIDON trial demonstrated that dual immunotherapy with durvalumab plus ipilimumab and chemotherapy significantly improved the outcome compared with chemotherapy alone as a first-line treatment strategy in advanced NSCLC.

• Recently, results from the phase I/II TRIDENT-1 clinical trial suggested that a novel tyrosine kinase inhibitor, repotrectinib, shows antitumor activity in ROS-1–positive advanced NSCLC patients, including those previously treated with other ROS-1 inhibitors. The findings have not yet been peer-reviewed or published.

• On November 10, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab (Imfinzi) and platinum-based chemotherapy for adult patients with metastatic NSCLC with no sensitizing EGFR mutation or ALK genomic tumor aberrations.

• Findings from a recent study show that levels of a key protein, TLR2, in tumors was found to predict a patient's survival after being diagnosed with lung cancer. In exploring the mechanics of the early stages of lung cancer, researchers may have also identified a new potential treatment, which could also aid early detection of the disease.

• In September 2022, the FDA granted regular approval to selpercatinib for adult patients with locally advanced or metastatic NSCLC with a rearranged during transfection gene fusion as detected by an FDA-approved test. The FDA also approved the Oncomine Dx Target Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib.

• Researchers recently indicated that in patients with NSCLC ineligible for standard chemotherapy, a first-line checkpoint inhibitor almost doubled overall survival at 2 years regardless of underlying histology, performance status, or PD-L1 expression.

• In August 2022, findings from phase III IMscin001 study evaluating a subcutaneous formulation of atezolizumab revealed that it met its coprimary endpoints. The study showed noninferior levels of atezolizumab pharmacokinetics, when injected SC, compared with IV infusion in cancer immunotherapy–naïve patients with locally advanced or metastatic NSCLC for whom prior platinum therapy has failed. The safety profile of the SC formulation was consistent with that of IV formulation. Data will be submitted to health authorities globally, including the FDA and European Medicines Agency.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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