Comparison of pemetrexed-free immunochemotherapy (atezolizumab/carboplatin/nab-paclitaxel) with standard immunochemotherapy (pembrolizumab/platinum/pemetrexed) in people with metastatic lung cancer (TTF-1 negative)

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, which also includes lung adenocarcinoma. It develops when certain cells in the lung multiply uncontrollably. “Non-small cell” means that the cancer cells appear larger under a microscope than those in the rarer form, small cell lung cancer. An “adenocarcinoma” originates from glandular cells that produce mucus, usually in the outer regions of the lung. This disease usually grows more slowly than small-cell lung cancer and, depending on the stage, can be treated with surgery, radiation, medication, or a combination of these. The specific treatment that is appropriate depends on how far the cancer has progressed and whether certain changes (mutations) are present in the tumor cells. In most of these tumors, a specific protein, “Thyroid Transcription Factor 1” (TTF-1), can be detected.

Metastasis means that cancer cells break away from the original tumor, travel through the bloodstream or lymphatic system, and form new tumors in other parts of the body. These are called metastases (secondary tumors). Once the cancer has formed metastases, surgery is usually no longer sufficient because the disease has spread throughout the body. Treatment then aims to slow the growth of the cancer, alleviate symptoms, and maintain quality of life. The standard first-line treatment for metastatic lung cancer is a combination of immunotherapy (so-called checkpoint inhibitors) and chemotherapy. This standard therapy often includes the chemotherapy drug pemetrexed. However, clinical evidence suggests that patients whose tumors do not produce TTF-1 (TTF-1-negative) may respond better to treatment without pemetrexed. Checkpoint inhibitors are drugs that reactivate the immune system so that it can better fight cancer cells.

The goal of the ANTELOPE study is therefore to evaluate the effectiveness of pemetrexed-free therapy in a direct comparison with standard therapy that includes pemetrexed. The most important outcome measure is overall survival. Participants in the study will be randomly assigned to two groups. Group A will receive the pemetrexed-free treatment: atezolizumab (immunotherapy), carboplatin (chemotherapy), and nab-paclitaxel (chemotherapy). Group B will receive the standard treatment containing pemetrexed: pembrolizumab (immunotherapy), cisplatin or carboplatin (chemotherapy), and pemetrexed (chemotherapy). The study is open-label, meaning it is not blinded; that is, medical staff and participants know which medications are being administered.

Eligible participants are women and men aged 18 and older who have been newly diagnosed with lung cancer exhibiting specific characteristics (metastatic, TTF-1-negative, PD-L1 < 50%). They must not have received any prior systemic treatment.