Immunotherapy: how clinical practice is changing for lung and bladder cancers

“For 20 years, the standard treatment has consisted of radical cystectomy, preceded by four cycles of cisplatin-based chemotherapy – says Lorenzo Antonuzzo, director of the Complex Unit of Clinical Oncology at the Careggi University Hospital, Department of Experimental and Clinical Medicine, University of Florence –. However, around half of patients experience a recurrence or progression of the disease, meaning there remains an unmet clinical need. The addition of immunotherapy with durvalumab, both before and after surgery, represents an innovative strategy that is changing clinical practice. It is the first perioperative immunotherapy regimen to demonstrate a statistically significant and clinically relevant improvement in overall survival in this patient population. In the NIAGARA study, published in the *New England Journal of Medicine*, a 25% reduction in the risk of death was recorded; indeed, 82.2% of patients treated with durvalumab were alive at 2 years, compared with 75.2% of those receiving neoadjuvant chemotherapy alone. Furthermore, a 32% reduction in the risk of disease progression, recurrence, failure to complete the planned surgery or death was observed.”

“A multidisciplinary approach is required for patients who are candidates for cystectomy,” explains Rodolfo Hurle, a urologist at the IRCCS Istituto Clinico Humanitas. Following histological diagnosis and radiological staging, treatment must be discussed within the multidisciplinary team, comprising key specialists including the urologist, oncologist, radiotherapist, radiologist and pathologist. Other professionals may also be involved, such as a psycho-oncologist, a nuclear medicine specialist, a geriatrician, a rehabilitation specialist and a nutritionist. The approval of the perioperative regimen with durvalumab makes multidisciplinary consultation even more important.”

“After 20 years, clinicians and patients finally have a new treatment option available to them,” continues Laura Magenta, assistant to the President of APS (PaLiNUro Association). “The psychological impact of a cystectomy can be difficult to cope with. It is essential that patients have access to psycho-oncological support and support from the Patients’ Association, and that they are informed and aware of the important innovations brought about by research that are now available to them.”

Another form of cancer, for which no progress had been made for over 40 years, is limited-stage small-cell lung cancer. AIFA has approved the reimbursement of durvalumab as monotherapy for the treatment of patients with limited-stage small cell lung cancer whose disease has not progressed following platinum-based chemoradiotherapy. “In the ADRIATIC study, published in the *New England Journal of Medicine*,” emphasises Cesare Gridelli, “durvalumab reduced the risk of death by 27 per cent. The median overall survival was 55.9 months for durvalumab compared with 33.4 months for placebo, an improvement of almost 2 years. 56.5 per cent of patients treated with durvalumab were alive at three years, compared with 47.6 per cent on placebo. ADRIATIC is the first study to demonstrate progress with the use of immunotherapy following the traditional standard of care of concurrent chemoradiotherapy in limited-stage small cell lung cancer. The results represent a breakthrough for this aggressive disease, in which relapse rates are high, with only around 20 per cent of patients still alive at five years.”

“Small-cell lung cancer has, until now, received less attention than other cancers, partly due to the social stigma associated with the fact that the majority of patients have a history of smoking,” continues Silvia Novello. “The significant improvement in overall survival observed with durvalumab following concurrent chemoradiotherapy is transforming the treatment of the disease even in the limited stage, following the significant results already demonstrated by immunotherapy in the extensive stage.”

Immunotherapy is also making significant progress in the most common gynaecological cancer, endometrial cancer, with an estimated 8,260 new cases in Italia in 2025. AIFA has approved durvalumab in combination with chemotherapy (carboplatin and paclitaxel) for the first-line treatment of patients with advanced or recurrent primary endometrial cancer with mismatch repair (dMMR), who are candidates for systemic therapy, followed by maintenance treatment with durvalumab as monotherapy.

“Around 30 per cent of patients present with the disease alongside a mismatch repair deficiency, that is, a malfunction in the DNA repair mechanism – says Domenica Lorusso, Head of the Gynaecological Oncology Centre at Humanitas San Pio X and Full Professor of Obstetrics and Gynaecology at Humanitas University. – In the DUO-E trial, in patients with this particular biological characteristic, durvalumab plus chemotherapy followed by durvalumab monotherapy demonstrated a 58% reduction in the risk of disease progression or death compared with chemotherapy alone. “Thanks to AIFA’s approval, the addition of durvalumab to chemotherapy represents a new first-line treatment strategy for these patients.”

“For many years, the treatment options for most women with advanced endometrial cancer have remained unchanged, and the standard of care has traditionally been limited to chemotherapy,” explains Nicoletta Colombo, director of the Gynaecological Oncology Programme at the European Institute of Oncology in Milan. “The introduction of immunotherapy for advanced disease now enables us to achieve significant and lasting responses, particularly in patients with a mismatch repair deficiency. Molecular classification of the tumour is essential from the moment of diagnosis in order to establish the correct treatment pathway, which is becoming increasingly personalised.”

“Endometrial cancer is one of the most common gynaecological cancers, but there is still little awareness of this condition,” says Manuela Bignami, Director of Loto OdV. “Furthermore, it does not receive the necessary attention in health policies, despite its high incidence. It is essential to recognise its priority by placing it at the heart of prevention, diagnosis and treatment strategies.”

“Italia continues to play a leading role in innovation in oncology,” concludes Paola Morosini, Head of Medical Affairs for Oncology at AstraZeneca. AstraZeneca is conducting 110 clinical trials in oncology, 15 of which are in Phase 1, and we have invested $14.2 billion in global Research and Development in 2025. We want to bring the benefits of immuno-oncology to as many patients as possible. Perioperative treatment approaches – which combine the benefits of immunotherapy before and after surgery – are becoming increasingly important, particularly in patients with non-small cell lung cancer and muscle-invasive bladder cancer.”