Lung cancer: monoclonal antibody conjugate reduces the risk of disease progression

Imagine a postman. His job is to take letters exactly to the person who is meant to receive them, and to hand them over personally. Now transfer this image to the invisible world of non-small cell lung cancer – by far the most common form of the disease. The postman, who manages to gain access to the diseased cells by recognising the exact ‘lock’, guides the treatment to where it is needed. And once inside the tumour, he releases the drug that kills the tumour cell itself. In the era of drug-conjugated monoclonal antibodies, this approach is also becoming a reality in the treatment of lung cancer. Treatment with trastuzumab deruxtecan – the name of this monoclonal antibody conjugate – has produced a statistically significant and clinically relevant improvement in progression-free survival (PFS) compared with the standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as first-line treatment for patients with HER2-mutated, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer. The reduction in the risk of disease progression or death compared with pembrolizumab plus chemotherapy was 37 per cent.

“Every year in Italia, there are an estimated 45,000 new cases of lung cancer,” reports Silvia Novello, president of WALCE (Women Against Lung Cancer in Europe), Professor of Medical Oncology at the University of Turin and Head of Medical Oncology at the San Luigi Gonzaga University Hospital in Orbassano –. HER2-mutated non-small cell lung cancer is an aggressive disease, for which current first-line treatment standards are of limited efficacy and many patients experience disease progression within a year of starting treatment. “With an objective response rate of 70 per cent and a median progression-free survival of 14.3 months, trastuzumab deruxtecan certainly has the potential to become a new first-line treatment option for these patients.”

“Around 4 per cent of patients with non-small cell lung cancer have a mutation in the HER2 protein,” explains Antonio Passaro, director of the Division of Thoracic Oncology at the European Institute of Oncology (IEO) in Milan. The presence of the HER2 mutation makes the tumour sensitive to drugs that target this specific molecule. Trastuzumab deruxtecan combines a monoclonal antibody with a cytotoxic agent and is highly selective for tumour cells, minimising damage to surrounding healthy cells and increasing the effectiveness of treatment in patients with HER2-mutated cancer. It is important to distinguish the HER2 mutation from the overexpression of this protein. These are biologically distinct alterations and do not necessarily identify the same patients. The results of the DESTINY-Lung04 study reinforce the importance of comprehensive molecular profiling at the time of diagnosis, so as to identify even less common but treatable alterations.” In terms of safety, the safety profile of trastuzumab deruxtecan observed in the DESTINY-Lung04 study was generally consistent with what was already known.