This year’s ESMO 2024 Congress brought a record of 34,000 participants from 149 countries to Barcelona. A congress which showcased the latest advancements in oncology, covering a wide spectrum of topics from groundbreaking research to clinical studies which will be changing the way cancer patients are treated.
Here’s a summary of the key themes that caught my attention – Enjoy!
Key Study Updates
On ADCs
Antibody-drug conjugates (ADCs) are transforming the treatment landscape for patients with advanced breast cancer, offering new hope where other options have fallen short. Research presented at the ESMO Congress 2024 highlighted both the expansion of current ADC applications to a broader patient population and the exploration of novel ADCs targeting new, emerging biomarkers.
Antibody–drug conjugates offer hope for patients with breast cancer including patients with brain metastases
The late-breaking results from the DESTINY-Breast-12 trial demonstrated the substantial and lasting efficacy of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer, notably including those with brain metastases. This is particularly significant as brain metastases are common in this patient population and previously often required radiation therapy with potential toxicity. The positive outcomes, even in those with active brain metastases, challenge prior concerns about the drug’s ability to cross the blood-brain barrier, suggesting a systemic approach could effectively treat advanced breast cancer with brain metastases.
Additionally, the ICARUS-BREAST01 study showcased promising results for patritumab deruxtecan, a novel anti-HER3 ADC, in HR-positive/HER2-negative breast cancer patients who progressed on standard therapies. With manageable side effects and compelling efficacy, it could represent a future treatment option in this setting.
While ADCs are already approved for metastatic breast cancer, their potential integration into earlier treatment lines and the optimal sequencing of multiple ADC options remain areas of active research. Furthermore, a deeper understanding of biomarkers such as expression of HER3 and HER2-low identification and their association with outcomes, as well as expanding eligibility criteria for ADC treatment, are key areas for future investigation. The ongoing research into ADCs fuels optimism for more personalized and effective treatment options for breast cancer patients.
The ADRIATIC study’s subgroup analyses provide further evidence to support the practice- changing impact of the initial findings
Subgroup analyses from the ADRIATIC trial continue to support the use of durvalumab consolidation therapy in patients with limited-stage small cell lung cancer (LS-SCLC) who have not progressed after chemoradiotherapy. The benefits of durvalumab in terms of overall survival (OS) and progression-free survival (PFS) were observed regardless of prior prophylactic cranial irradiation (PCI) or type of chemotherapy used. While some differences in outcomes were seen between subgroups based on PCI and radiotherapy schedule, these are likely due to baseline patient characteristics rather than treatment effect. Importantly, the safety profile of durvalumab was favourable, even in patients who had received prior radiation. These findings solidify the practice-changing role of durvalumab in improving outcomes for patients with LS- SCLC, bringing the possibility of cure closer to reality.
Multi-gene ctDNA Testing Improves Treatment Selection for Advanced Cancer
Two trials conducted at the Institute Gustave Roussy, demonstrated that comprehensive ctDNA analysis effectively identifies actionable genomic alterations in patients with advanced cancer, guiding them towards suitable targeted therapies. The STING and PRISM-POrTAL trials evaluated over 8,500 patients, resulting in therapeutic recommendations for approximately 57% of patients in both trials. Dr. Alexander Wyatt, while endorsing the practicality of ctDNA profiling, cautions that it’s not always suitable due to the potential for false negatives and positives. He emphasizes the need for clinical trials to establish the clinical value of ctDNA-derived information and for clearer reporting practices. Future advancements, incorporating whole-genome sequencing (WGS) and DNA methylation profiling, are expected to enhance ctDNA analysis further. To expand access to this technology, Gustave Roussy has launched the FRESH program, promoting the use of liquid biopsies in precision oncology throughout France.
New Cancer Vaccine and Immunotherapy Offer Hope for High-Grade Glioma Patients
Three presentations at the ESMO Congress 2024 showcased therapies aimed at enhancing the body’s immune response against aggressive high-grade gliomas. Firstly, an initial trial of the GBM-directed mRNA vaccine CVGBM demonstrated good tolerability with promising immune responses in patients with resected MGMT-unmethylated grade 4 disease. Secondly, a phase I trial combining intracranial ipilimumab and nivolumab with autologous dendritic cells showed encouraging survival rates in patients with recurrent high-grade glioma, although further validation is needed due to study limitations. Lastly, intrathecal administration of allogeneic CAR ɣδT cells targeting B7H3 resulted in objective responses and disease control in patients with recurrent GBM, with no dose-limiting toxicities observed. These early-phase findings suggest a potential role for innovative immunotherapy approaches in improving outcomes for this challenging disease.
Combination Immunotherapy and Chemotherapy Improves Anal Cancer Treatment
The phase III PODIUM-303 trial has demonstrated a significant advancement in the treatment of unresectable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC), when adding the anti-PD-1 immunotherapy retifanlimab to standard chemotherapy. It has led to improved PFS compared to chemotherapy alone (SCAC; 9.3 months versus 7.4 months; hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.47–0.84; p=0.0006), results suggesting that the combination therapy with ICI may become a new standard of care for SCAC. While OS data are still maturing, a positive trend favouring the retifanlimab arm has been observed. Future research will focus on exploring the potential of retifanlimab in earlier stages of SCAC and investigating further intensification of immunotherapy in this cancer type.
Immunotherapy Boosts Survival for Muscle-Invasive Bladder Cancer
The results from the NIAGARA trial have shown that addition of durvalumab to neoadjuvant chemotherapy and continuing it as adjuvant therapy after surgery, leads to significant improvements in both event-free survival (EFS) and OS compared to chemotherapy alone, in localized muscle-invasive bladder cancer (MIBC). This breakthrough is particularly impactful as it not only met its primary endpoint of EFS but also showed a significant extension in OS, a more challenging goal. The safety profile was reassuring, with manageable toxicity and no new safety concerns. Future research will focus on addressing remaining questions, such as the optimal timing of ICIs administration and the role of ctDNA in this setting.
Pembrolizumab and Chemoradiotherapy Extend Survival in Locally Advanced Cervical Cancer
Encouraging data from phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study has shown an OS benefit for high-risk, locally advanced cervical cancer patients treated with pembrolizumab and concurrent chemoradiotherapy (36-mo OS rate of 82.6% for pembro plus concurrent CRT and 74.8% for placebo plus concurrent CRT (hazard ratio [HR] 0.67; 95% confidence interval [CI], 0.50–0.90; p=0.0040). This combination therapy, offering a greater chance of cure, is poised to become the new standard of care, despite the increased treatment duration (2y) and associated costs. While the benefits of this treatment are substantial, its high cost poses a significant barrier to access, particularly in lower- and middle-income countries where cervical cancer is most prevalent.
Early Immunotherapy Shows Significant Survival Benefit in Triple-Negative Breast Cancer (TNBC)
The final results from the KEYNOTE-522 study confirm the significant impact of adding pembro to standard chemotherapy for patients with high-risk, early-stage TNBC. This combination therapy has demonstrated improvements in OS (5-year OS rates were 86.6% versus 81.7%) and EFS (5-year EFS rate was 81.2% in the pembro arm vs 72.2% in the placebo arm), solidifying its potential as a new standard of care. However, it’s crucial to carefully select patients for this treatment and closely monitor them for potential toxicities, since the 5-year EFS was 72.2% in the placebo arm, showing that many patients are doing well with chemotherapy alone. It is important to identify those who are most likely to benefit from ICIs to avoid unnecessary immune-related side effects, while also economic impacts, access and availability of ICIs need to be addressed to ensure equitable access to this treatment.
Further research is needed to refine treatment strategies, including exploring less toxic chemotherapy regimens and various immunotherapy combinations. Biomarker research, monitoring of late-onset toxicities, and the development of personalized treatment approaches are also essential next steps.
Neoadjuvant Immunotherapy Improves Long-Term Survival in Stage III Melanoma
The International Neoadjuvant Melanoma Consortium analysis revealed high 3-year EFS rates with various combinations, particularly in patients achieving a major pathological response. The NADINA trial also reported significantly higher EFS and distant metastasis-free survival rates with neoadjuvant nivolumab plus ipilimumab compared to adjuvant nivolumab. These findings solidify neoadjuvant immunotherapy as the preferred standard of care for this patient population, offering improved long-term outcomes and potentially reducing the need for extensive adjuvant therapy.
However, OS benefits of systemic IO therapy in the adjuvant setting in stage III melanoma are still unclear in clinical trials, and may need to be complemented with real-world studies.
