The results of numerous large international studies reported at the European Society for Medical Oncology (ESMO) Congress 2024 showed that immunotherapy improves long-term overall survival in patients with a variety of cancer types, including advanced melanoma,1,2 triple-negative breast cancer,3 and muscle-invasive bladder cancer.4
Alessandra Curioni-Fontecedro, MD
“The main message from all of these studies is that immunotherapy continues to keep its promise and hope of long-term survival for many patients with different types of cancer,” said Alessandra Curioni-Fontecedro, MD, Professor of Oncology at the University of Fribourg and Director of Oncology at the Hospital of Fribourg, Switzerland. “At ESMO 2024, we are seeing many studies in many different cancers showing that immunotherapy can work for a long time.”
Advanced Melanoma
Results of a phase III trial of immunotherapy with an anti–PD-1–based therapy showed continued long-term survival benefit in patients with advanced melanoma.1 After follow-up of at least 10 years, the median overall survival was 71.9 months in patients randomly assigned to combination immunotherapy with nivolumab plus ipilimumab in the CheckMate 067 trial. Few of the patients showing a good initial response to anti–PD-1–based immunotherapy, with no disease progression for at least 3 years, had died of melanoma at 10 years (10-year melanoma-specific survival rate = 96%). The researchers suggested there is now a potential for cure in patients responsive to these treatments.
Marco Donia, MD, PhD
“The results from this trial do confirm the potential for cure with immunotherapy in patients with advanced melanoma,” agreed Marco Donia, MD, PhD, Associate Professor of Clinical Oncology at the National Center for Cancer Immune Therapy of Denmark, Copenhagen University Hospital Herlev. He added: “For patients who show no disease progression beyond 3 years, these longer-term results demonstrate that most of them never [have disease progression]. The melanoma-specific survival is very high in this group of patients.”
Triple-Negative Breast Cancer
Improved overall survival with immunotherapy was also reported in early-stage triple-negative breast cancer. Results showed a statistically significant and clinically meaningful improvement in overall survival with immunotherapy plus chemotherapy before surgery and continued immunotherapy after surgery. The 5-year overall survival rate was 86.6% in patients given immunotherapy and 81.7% in the placebo group.3
“This study shows improvements with immunotherapy in patients with the most aggressive subtype of breast cancer, where previously we could only offer chemotherapy,” said Dr. Curioni-Fontecedro. “We had thought that breast cancer may not be sensitive to immunotherapy alone, but giving it in combination with chemotherapy before surgery and then further afterward improves overall survival in many patients. The finding suggests the possibility that the combination of treatments might lead to a sensitization of triple-negative breast cancer to immunotherapy.”
Muscle-Invasive Bladder Cancer
A similar improvement in overall survival with giving immunotherapy before surgery was seen in a study of patients with muscle-invasive bladder cancer.4 The phase III NIAGARA study randomly assigned patients to immunotherapy with durvalumab plus chemotherapy before radical cystectomy followed by continued immunotherapy or chemotherapy alone before surgery. Patients treated with immunotherapy showed significantly longer event-free survival (hazard ratio [HR] = 0.68; 95% confidence interval [CI] = 0.56–0.82; P < .001) and overall survival (HR = 0.75; 95% CI = 0.59–0.93; P = .0106) compared with those receiving chemotherapy alone. The researchers noted that giving immunotherapy before surgery did not seem to compromise the ability to perform radical cystectomy, which was completed in 88% of the immunotherapy group and 83% of the comparator arm.
Unanswered Questions
Looking to the future of research with immunotherapy, Dr. Curioni-Fontecedro shared these comments: “We still have some major questions that are unanswered. The first is understanding why cancers recur in some patients despite initial response to immunotherapy. We still don’t understand how resistance to immunotherapy can occur in some patients. We need to understand what happens in these patients, what are the mechanisms of resistance, and how we can overcome them.”
She suggested that it is important for clinical researchers and pharmaceutical companies to work together to approach the issue of resistance to immunotherapy effectively. “As long as the issue of resistance is investigated in isolation, looking at individual immunotherapy agents, it will not be enough. We should all put our forces together to improve understanding and promote better treatment for the future.”
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session.
REFERENCES
1. Larkin J, Chiarion Sileni V, Gaudy Marqueste C, et al: 10-y survival outcomes from the phase 3 CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma. ESMO Congress 2024. Abstract LBA43. Presented September 15, 2024.
2. Robert C, Carlino MS, McNeil C, et al: Pembrolizumab vs ipilimumab in advanced melanoma: 10-year follow-up of the phase 3 KEYNOTE-006 study. ESMO Congress 2024. Abstract LBA44. Presented September 15, 2024.
3. Schmid P, Cortes J, Dent RA, et al: Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase 3 KEYNOTE-522 study. ESMO Congress 2024. Abstract LBA4. Presented September 15, 2024.
4. Powles TB, van der Heijden MS, Galsky MD, et al: A randomized phase 3 trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). ESMO Congress 2024. Abstract LBA5. Presented September 15, 2024.
