A combination therapy improves survival of patients with small cell lung cancer, a rapidly progressing lung cancer.
There has been a lot of talk about lung cancer in recent weeks, with the discovery and removal of a lung nodule (later the result of lung adenocarcinoma) in Pope Leo XIV. But on October 24, it was another type of lung tumor that catalyzed the attention of the oncologists of the European Society of Medical Oncology (Esmo), gathered at a congress in Madrid: microcytoma or small cell lung cancer, against which a therapeutic breakthrough has perhaps been found.
The combination of two immunological drugs extended the median survival of patients suffering from this form of cancer, one of the most aggressive and fastest spreading, by 8.4 months, bringing it from 12.7 to 21.1 months.
Lung health experts call it a revolution, because the approach has managed to reverse the trajectory of the disease, hitting it at a stage when it is usually at a standstill and before it starts to progress again. The results of the international phase 3 study (DeLLphi-305 study) have been published in the prestigious medical journal New England Journal of Medicine.
The strategy: avoid the rebound effect
Microcytoma or small cell lung cancer (SCLC) is responsible for 10-15% of lung cancer cases and generally occurs in smokers. It spreads rapidly to other organs and therefore generally has a worse prognosis, because it is diagnosed when it has already spread outside the lung.
Furthermore, this tumor follows a trend defined as the “rebound effect”. Initially it responds to chemotherapy, showing a phase in which its progression stops, which however is followed by another phase in which it returns to running, leaving few therapeutic options.
Hitting the tumor during the stall phase
The tested strategy consists in hitting the microcytoma right during the “stall” phase, before it has time to orchestrate a recovery. During the study, led by Maurice Pérol, oncologist at the Léon Bérard Cancer Center in Lyon, France, 563 patients were involved who had completed standard therapy (chemotherapy plus immunotherapy with the drug durvalumab), divided into two groups to evaluate the best maintenance strategy. The first group continued with only durvalumab (current standard), the second combined the immunotherapy with a bispecific antibody, the tarlatamab.
This drug is designed to simultaneously engage two targets: on the one hand, a protein expressed in massive quantities on tumor cells, on the other, a receptor present on T lymphocytes, the white blood cells that recognize and destroy tumor cells.
The drug essentially acts as a bridge between the lymphocytes and the cells they are supposed to attack, forcing them to a close distance which facilitates the attack. Meanwhile, the other drug, durvalumab, deactivates a shield protein on tumor cells so that the immune system can recognize them.
Results and side effects
The combination was deadly for small cell carcinoma and led to a 58% drop in deaths one year after treatment. The two drugs used together increased the median time in which the tumor remained dormant, from 1.9 months to 7.4 months, and improved the response to treatment, with the tumor shrinking further in 26.4% of patients treated with the two immunotherapies, compared to 4.1% of patients in the standard group.
However, the treatment also triggered, in half of the patients, a systemic inflammatory reaction – the cytokine release syndrome, which involves fever, shortness of breath, tachycardia and a marked drop in blood pressure – due to the massive activation of the immune system, fortunately in a moderate form. An effect that justifies the administration of the therapy in specialized oncology centers. For now, however, we need to wait for regulatory bodies to approve tarlatamab (already used in the USA for relapses after chemo) also for the maintenance phase.
