More good news from the congress ESMO 2024 Of Barcelona (13-17 September) on the use of immunotherapy in the treatment of different types of tumors.
During the oncology meeting, several international studies were presented demonstrating how immunotherapy, by enabling the immune system to recognize and destroy tumor cells, can improve overall survival in patients with advanced melanoma, early-stage triple-negative breast cancer, and muscle-invasive bladder cancer.
Immunotherapy
«The main message from all these studies is that immunotherapy continues to hold its promise and the hope of long-term survival for many patients with many types of cancer.“, said Dr. Alessandra Curioni-FontecedroProfessor of Oncology at the University of Fribourg and Director of Oncology at the Fribourg Hospital (Switzerland). «All’ESMO 2024 – he continued – We are seeing many studies on many different cancers showing that immunotherapy can work in the long term».
Indeed, the results of the phase 3 study (CheckMate 067), conducted on 945 patients with advanced melanoma, have shown a benefit, in terms of long-term survival, deriving from treatment with immunotherapy.
Very few patients who showed a good initial response to immunotherapy, with no disease progression for at least 3 years, died of melanoma after 10 years.
Surviving Melanoma
Prof. Marco DoniaA 10-year melanoma-specific survival rate of 96% was observed. «For patients who show no disease progression beyond three years, these long-term results show that the majority of them never progress. Melanoma-specific survival is very high in this group of patients.“, said Dr. Marco DoniaAssociate Professor of Clinical Oncology at the National Center for Cancer Immune Therapy of Denmark, Copenhagen University Hospital Herlev (Denmark).
Prof. Donia also highlighted that the long-term survival benefit with immunotherapy is also seen in routine clinical practice, outside of clinical trials.
«Immunotherapy – continued the researcher of Catania origins – transformed advanced melanoma from what was previously a deadly disease with an average survival of less than a year to what we see today, with half of patients surviving for many years“. This naturally raises practical questions about how best to follow up these patients, including the need for long-term follow-up.
Immunotherapy plus chemotherapy.
Prof. Marco Donia – ESMO press conferenceVery promising results also come from the international phase 3 study (KEYNOTE-522), which evaluated the efficacy of immunotherapy (pembrolizumab) in 1,174 women affected by a particular molecular subtype of breast cancer, called triple-negative.
In general, triple-negative breast cancers are particularly difficult to treat, as they are characterized by the absence of expression of estrogen receptors, progesterone receptors and HER2, and therefore do not respond to the biological therapies commonly used for breast cancer.
The study results showed a statistically and clinically significant improvement in overall survival following treatment with immunotherapy plus chemotherapy before surgery followed by immunotherapy after surgery.
The five-year overall survival rate was 86.6% in patients treated with immunotherapy (pembrolizumab + chemotherapy – surgery – pembrolizumab) and 81.2% in the placebo-treated group (placebo + chemotherapy – surgery – placebo).
«This study – stated the Professor Curioni-Fontecedro – shows improvements with immunotherapy in patients with the most aggressive subtype of breast cancer, where we previously could only offer chemotherapy. We had thought that breast cancer might not be responsive to immunotherapy alone, but giving it in combination with chemotherapy before surgery and then further afterward improves overall survival in many patients. The finding raises the possibility that the combination of treatments may lead to sensitization of triple-negative breast cancer to immunotherapy».
Bladder cancer
A similar improvement in overall survival following administration of immunotherapy (durvalumab) before surgery was also observed in a phase 3 study (NIAGARA) conducted in 1,063 patients with muscle-invasive bladder cancer.
Muscle-invasive bladder cancer is a cancer that can spread locally to invade the muscle layers and the entire bladder wall. It is a more serious and advanced stage of bladder cancer, one of the most aggressive, which requires as a standard treatment the use of chemotherapy before surgery, followed by radical cystectomy, that is, a destructive surgical procedure.
Fifty percent of patients typically experience recurrence (return of the disease). Radical cystectomy involves removal of the bladder, prostate, seminal vesicles, distal ureter, and pelvic lymph nodes. Approximately half of the patients in the NIAGARA study received immunotherapy with durvalumab plus chemotherapy before radical cystectomy, followed by immunotherapy post-surgery. The other half of the patients received chemotherapy alone before surgery (radical cystectomy).
The response of patients treated with immunotherapy
Patients treated with immunotherapy (durvalumab) showed significantly longer overall survival than those treated with chemotherapy alone, with a tolerable toxicity profile. Treatment with durvalumab before and after surgery reduced the risk of recurrence by 32% and the risk of death by 25%.
The researchers also noted that administering immunotherapy before surgery did not compromise the ability to perform radical cystectomy, which was performed in 88% of patients who received immunotherapy. The results of the NIAGARA study, presented at the ESMO 2024 Presidential Symposium, were simultaneously published in the prestigious international journal The New England Journal of Medicine.
AIOM Press Conference – Boldrini and Di Maio«The standard treatment for about 20 years has been chemotherapy followed by surgery, but half of patients experience disease recurrence or progression, leaving an unmet clinical need.», underlined Prof. Max DiMaioPresident-elect AIOM (Italian Association of Medical Oncology).
Di Maio also specified that «In managing the disease and ensuring the best therapeutic path, a multidisciplinary team is essential, which must include, among others, the radiologist, the surgeon, the oncologist, the urologist and the pathologist». «The goal is to try to avoid having to resort to demolitive surgery.», concluded Di Maio.
NIAGARA studio
«The NIAGARA study demonstrates that the addition of durvalumab immunotherapy before and after surgery may represent an innovative, practice-changing strategy for patients with operable invasive urothelial bladder cancer.“, stated Prof. during the AIOM press conference. Lorenzo AntonuzzoDirector of the Complex Structure of Clinical Oncology of the Careggi University Hospital, Department of Experimental and Clinical Medicine (University of Florence).
Lorenzo Antonuzzo – AIOM Press Conference«There is still a lack of predictive factors of response to treatment, i.e. molecular alterations that predict whether a patient will respond to therapy or not.», underlined Lorenzo Antonuzzo.
Bladder cancer is one of the most common: in 2023, 29,700 new cases were detected in Italy. It is a sneaky neoplasm, because in the initial stages it can be completely asymptomatic. The first warning signs are urinary symptoms, such as difficulty urinating, frequent urination and the presence of hematuria, that is, blood in the urine.
The main risk factor is cigarette smoking, to which is added the occupational exposure to certain carcinogenic substances, such as aromatic amines and nitrosamines. Therefore, more anti-smoking campaigns should be promoted, in order to implement prevention strategies against bladder cancer, debunking the common idea that smoking can only be associated with the onset of lung cancer.
We still have so many things to understand
«We still have some important unanswered questions. – declared the Professor Curioni-Fontecedro – The first is to understand why tumors recur in some patients, despite the initial response to immunotherapy. We do not yet understand how resistance to immunotherapy can occur in some patients. We need to understand what happens in these patients, what the mechanisms of resistance are, and how to overcome them.».
Daniele Fanale