Microcytoma, the space for immunotherapy is growing for the rarest and most difficult lung cancer

Do you know an oat grain? Well, somehow when one speaks of a microcytoma, which accounts for about 15% of cancers affecting the lung, this definition is reminiscent of the particular microscopic conformation of the cells that cause it. Unfortunately, this form, no matter what it is called, is extremely fearsome. It tends to spread faster than adenocarcinoma (i.e. the most common form with over 80% of lung cancer cases), and develops very rapidly, although the size of the lesion may remain very small. This is why it happens that the tumour is recognised when the cancer cells are already present in the blood and the disease has therefore spread. Precisely for this form of the disease, research is proposing ever new solutions that reach the patient's bedside. The Italian Medicines Agency (AIFA) has approved the reimbursability of serplulimab, the first anti-PD-1 authorised in Europe for naïve, i.e. not pre-treated, patients with large-stage small cell lung cancer. The addition of the immunotherapy to chemotherapy demonstrated a significant and durable clinical benefit. Improvements in overall survival and disease-free progression maintained up to 4 years of follow-up were obtained.

Cigarette smoking is the main risk factor for the development of this form of cancer. Indeed, the inflammation induced by smoking and the presence of toxic elements (carcinogens and cocarcinogens) facilitate the transformation of healthy cells into cancer cells. 'Lung carcinoma in Italia accounts for more than 44,800 new diagnoses every year,' reports Federico Cappuzzo, Director of Medical Oncology 2 at the Regina Elena National Cancer Institute in Rome. Small-cell cancer is also called microcytoma and is an infrequent disease, accounting for 15% of all cases. However, it is very aggressive and has a severe prognosis. Among the different subtypes of thoracic cancer, it is undoubtedly the most related to smoking, which is the main risk factor'. It is estimated that some 70%-80% of patients already have extensive disease at the time of diagnosis. 'Available treatment options, for many decades, have been limited to a few chemotherapeutic drugs administered together with platinum derivatives,' the expert points out. Surgery is also rarely indicated, precisely because of the very aggressive nature of the neoplasm'.

The approval by AIFA follows the results of ASTRUM 005, a phase III, randomised, double-blind, multicentre, placebo-controlled trial in combination with chemotherapy. A total of 585 previously untreated patients were recruited. At four years, the survival of patients treated with serplulimab was 21.9%. The study then demonstrated a 40% reduction in the risk of death by extending survival by 4.7 months. The reduction in the risk of disease progression was 53%. 'Thanks to the efficacy results obtained and the favourable safety profile, serplulimab may be a valid first-line therapeutic option,' reports Silvia Novello, Professor of Medical Oncology at the University of Turin. 'Thanks to its mechanism of action, the drug is characterised by a more complete immune activation due to the inhibition of the PD-L1 and PD-L2 dual pathway. Serplulimab binds to the surface of activated T lymphocytes expressing PD-1 and blocks binding to the PD L1 and PD L2 ligands. It thus enhances cell responses, including anti-cancer responses. Moreover, the treatment was found to be well tolerated by the majority of patients'.