Additional radiation therapy in combination with chemotherapy and durvalumab, followed by maintenance therapy with further high-precision radiation therapy for advanced small-cell lung cancer

Lung cancer develops when cells in the lungs multiply uncontrollably and form tumors. Small cell lung cancer (SCLC) is considered aggressive and can spread throughout the body early in the course of the disease. Treatment depends on the extent of the disease. The disease is classified into three stages. In the very limited stage (VLD), the tumor is still small and confined to a limited area of the lung, so surgery or targeted radiation therapy aimed at completely removing the tumor may still be possible. In the limited stage (LD), the cancer is confined to one lobe of the lung and nearby lymph nodes. A combination of chemotherapy and radiation therapy is an option in this case. In the extensive stage (ED), the cancer has already spread to other organs or distant lymph nodes (metastases), so targeted radiation therapy can no longer be used, and systemic therapy—that is, chemotherapy and immunotherapy—is necessary instead. At this stage of the disease, the goal of treatment is disease control (palliative therapy), since it must be assumed that the tumor can no longer be cured. The disease is described as oligometastatic when the cancer has already metastasized but only a few (usually up to five) metastases are present outside the lungs. The standard treatment for ED-SCLC consists of a combination of chemotherapy (etoposide + carboplatin or cisplatin) and immunotherapy (e.g., durvalumab or atezolizumab). If the disease responds to treatment, immunotherapy is continued alone as maintenance therapy after four to six cycles of chemotherapy. In the study, the already approved drug durvalumab is used for immunotherapy; it is an antibody against the PD-L1 surface protein on cancer cells. PD-L1 normally prevents the body’s own immune cells from attacking the cancer. Durvalumab supports the immune system by blocking this protective barrier of the cancer cells. When chemotherapy is combined with radiation, it is called chemoradiation. In limited-stage disease, this type of treatment is already part of the standard of care. Another form of treatment is so-called stereotactic radiation therapy, a highly precise radiation treatment that uses very high doses to specifically destroy individual tumor foci or metastases and has so far been used primarily for brain metastases.

The goal of the DuCoRa-SCLC study is to investigate whether a combination of chemoradiotherapy with durvalumab, followed by maintenance therapy in conjunction with stereotactic radiation, can control tumor growth more effectively than the current standard of care.

The study is single-arm, meaning all patients will receive the study treatment. After enrollment in the study, patients will receive combined chemoradiotherapy. They will receive two additional cycles (22 days each) of chemotherapy with etoposide and either cisplatin or carboplatin in combination with durvalumab every three weeks. Radiation therapy is initially directed at the primary tumor and the affected lymph nodes in the chest area. Thereafter, during maintenance therapy with durvalumab every 4 weeks, patients also receive stereotactic radiation therapy to specifically target their metastases. The treatment provided as part of the study is experimental; however, chemotherapy combined with immunotherapy, as well as maintenance therapy with durvalumab alone, are already approved standard treatments. but the combination of chemotherapy/immunotherapy with radiation has not yet been approved for this disease, nor has stereotactic radiation during maintenance therapy. However, these procedures are already used as standard practice for other tumor stages. The study will monitor the effectiveness of this treatment for up to 12 months, with particular attention paid to the time without further disease progression (progression-free survival).

Women and men aged 18 and older who have extensive-stage (ED) small-cell lung cancer (SCLC) are eligible to participate in the study. The disease must be oligometastatic, meaning it must have fewer than five metastases and no fluid accumulation between the lungs and the pleura containing tumor cells (malignant pleural effusion). The lung cancer must have responded well to two previous cycles of chemotherapy (platinum, etoposide, and durvalumab). Brain metastases are not a criterion for exclusion from participation.