ESMO23: Diaceutics’ key takeaways

The European Society for Medical Oncology (ESMO) Congress 2023, held in Madrid from October 20^th to 24^th, brought together thousands of oncology professionals, researchers, and industry leaders who shared the latest breakthroughs and innovations in cancer care. Diaceutics were there to gain knowledge from the world-leading experts and provide insights and advice to our customers on the new findings.

Our precision medicine expert Tessa Sandberg attended the Congress and shared her daily highlights on our social media channels. In this blog post, we will recap some of the key insights from the four days of the conference, focusing on precision medicine topics such as biomarker testing, targeted therapies, and companion diagnostics.

Day 1: Promising results for radioligand therapy, pembrolizumab, and HER2 testing

The first day of the congress featured several presentations on novel therapies and biomarkers for various types of cancers. Some of the highlights were:

• Promising results of enzalutamide + radioligand therapy in metastatic castration resistant prostate cancer (mCRPC): The ENZA-p trial showed a survival benefit for the combination versus enzalutamide alone. This is the first trial to combine enzalutamide with radioligand therapy in mCRPC, and the results suggest that this combination could become a new standard of care.
• Benefit of adding pembrolizumab to trastuzumab and chemotherapy in HER2+ gastric/esophagogastric junction (Gastric/GEJ) in first line therapy: The KEYNOTE-811 trial showed an OS and PFS benefit, especially in PD-L1 positive cancers. These results led to the EMA approval this year in PD-L1 positive gastric/GEJ cancers.
• HER2 testing in metastatic colorectal cancer (mCRC) may shift to earlier line: The results of MOUNTAINEER-03 trial are in progress, testing trastuzumab and tucatinib in 1L HER2+ and RAS WT mCRC. A poll at the conference showed that nearly all respondents (92%) believe HER2 testing should be performed at diagnosis of metastatic disease. However, ESMO guidelines do not (yet) recommend this. This suggests that we may see a shift towards earlier HER2 testing in mCRC, which could lead to more patients benefiting from targeted therapies. At Diaceutics, we believe that every patient should receive the right test and the right treatment to positively impact their disease outcome, and we strongly encourage the uptake of early testing for better treatment.

Day 2: Rare mutations in NSCLC get new targeted therapies

The second day of the congress focused on therapies targeting rare mutations in non-small cell lung cancer (NSCLC). At Diaceutics we understand the importance of comprehensive testing early on to find the right patient for the right drug. Some of the highlights were:

• 1L amivantamab plus chemotherapy showed survival benefit in advanced NSCLC with an EGFR exon 20 insertion: The PAPILLON trial established a new standard of care for patients with this rare mutation. Amivantamab plus chemotherapy in NSCLC with an EGFR exon 20 insertion significantly improved survival compared to chemotherapy alone, and these results are likely to lead to adoption of this combination in clinical practice.
• 1L selpercatinib showed survival benefit in RET fusion+ NSCLC: The LIBRETTO-431 trial showed a PFS benefit for selpercatinib as a first-line therapy of choice compared to chemotherapy and pembrolizumab. This is the first time that a targeted therapy has been shown to outperform immunotherapy in this setting, and it highlights the importance of precision medicine in the treatment of NSCLC. The evidence of this trial will hopefully lead to reimbursement in European countries where it was pending the results of this trial.
• Significant benefit of adjuvant alectinib versus chemotherapy in ALK+ early-stage NSCLC: The interim analysis ALINA trial showed a DFS and safety benefit for alectinib compared to chemotherapy. While awaiting the OS data, these positive results of ALK inhibition may lead to practice changes for patients with ALK+ early-stage NSCLC.
• Durable response of zenocutuzumab in advanced NSCLC with a NRG1 fusion: The eNRGy phase 2 trial showed promising durable efficacy for zenocutuzumab, a HER2 x HER3 bispecific antibody in NRG1+ advanced NSCLC. The authors argued that zenocutuzumab represents the first and best in class therapy for NRG1+ NSCLC.

Day 3: Breast cancer and immunotherapy get new developments

On the third day of the conference unique results were presented in bladder cancer. While these drugs do not require predictive testing, they impact current testing and treatment practices.

• Enfortumab Vedotin in combination with pembrolizumab (EV+P) as new 1L therapy in advanced metastatic bladder cancer: The presentation of the final results of the KEYNOTE-A39 clinical trial gained a standing ovation as results showed EV+P outperforming chemotherapy for the first time in 1L bladder cancer. A second trial, the CheckMate 901, showed the benefit of nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone in unresectable or metastatic bladder cancer. Similar to KEYNOTE-A39, the CheckMate 901 trial outperformed the current standard of care in 1L bladder cancer. However, it did not outperform the KEYNOTE-A39 results. The KEYNOTE-A39 trial showed a PFS and OS benefit for EV+P over chemotherapy. This is the first time that an immunotherapy combination has been shown to outperform chemotherapy in first-line advanced metastatic bladder cancer, and it establishes EV+P as a new standard of care in this setting.
• Encouraging anti-tumor activity and safety of RMC-6236, first in class, in NSCLC and PDAC with different genotypes in KRAS G12X: RMC-6236 is a highly innovative RAS-selective inhibitor with the potential to treat a wider range of RAS-mutated cancers, including KRAS G12D and G12V. The early-phase results presented at ESMO 2023 were encouraging, showing anti-tumor activity and a favorable safety profile.

Day 4: Novel approaches for melanoma, ovarian cancer, and glioblastoma

The fourth and final day of the congress presented novel approaches for melanoma, ovarian cancer, and glioblastoma. Some of the highlights were:

• Center of Excellence for the successful adoption of a complex test in a German academic laboratory - a case study: Following the promising results of the PAOLA-1 clinical trial in 2019, Germany prepared for the adoption of Homologous Recombination Deficiency (HRD), a biomarker tested with a complex assay. The Marburg lab implemented a Myriad MyChoice test to give German patients access to the drug upon launch. At Diaceutics, we know that testing is key for drug adoption and setting up a center of excellence is a great short-term opportunity to adopt testing. This case study highlights the importance of collaboration between academia and industry in the successful adoption of precision medicine approaches.
• Improvements in 1L and 2L treatment in EGFR-mutated metastatic NSCLC: The MARIPOSA and MARIPOSA-2 trials showed benefit over the standard of care for both 1L and 2L treatment of EGFR-mutated metastatic NSCLC. In MARIPOSA, amivantamab + lazertinib showed PFS benefit compared to osimertinib in 1L therapy. MARIPOSA-2 results showed that amivantamab plus chemotherapy with or without lazertinib vs chemotherapy is a new treatment option in 2L  post-osimertinib. With the increased number of treatment options in EGFR+ NSCLC, will there be a way to select which patients will benefit most from which treatment? For instance, using the biomarker MET for amivantamab targeting both EGFR and MET? These results suggest that we are making significant progress in improving outcomes for patients with this type of cancer.
• The future of digital pathology in clinical practice: In this special session, a pathologist highlighted the challenges of integrating digital pathology into clinical practice while acknowledging the potential to integrate complex biomarkers and improve patient management. For instance, through 1) reducing human error, 2) discovering new types of features, and 3) integrating multi-modal data. Digital pathology is a rapidly developing field with the potential to transform cancer diagnosis and treatment, and the discussion at ESMO 2023 highlighted the importance of this technology.

Conclusion

ESMO 2023 featured a number of promising new developments in cancer treatment and diagnostics, including new targeted therapies for rare mutations in NSCLC and new immunotherapies for bladder cancer. The conference also highlighted the growing importance of precision medicine and the need for more comprehensive testing at the time of diagnosis.

Diaceutics would like to extend our congratulations and thanks to every individual who helped to make these significant treatment breakthroughs possible. We were extremely proud to be part of this event and to share our insights and advice with our customers on the potential impacts of these new findings. We are committed to improving patient outcomes by enabling better testing and better treatment for precision medicine.

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References:

• LBA84 - Enzalutamide and 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer (mCRPC): a randomised, phase 2 trial: ENZA-p (ANZUP 1901)
• 1511O - Pembrolizumab plus Trastuzumab and Chemotherapy for HER2+ Metastatic Gastric or Gastroesophageal Junction (mG/GEJ) Adenocarcinoma: Survival results from the Phase 3, Randomized, Double-blind, Placebo-controlled KEYNOTE-811 Study
• Session organised by Seagen: HER2-Targeted Therapies in mCRC: Are We Ready for a Paradigm Shift?
• 𝘓𝘉𝘈5 - 𝘈𝘮𝘪𝘷𝘢𝘯𝘵𝘢𝘮𝘢𝘣 𝘗𝘭𝘶𝘴 𝘊𝘩𝘦𝘮𝘰𝘵𝘩𝘦𝘳𝘢𝘱𝘺 𝘷𝘴 𝘊𝘩𝘦𝘮𝘰𝘵𝘩𝘦𝘳𝘢𝘱𝘺 𝘢𝘴 𝘍𝘪𝘳𝘴𝘵-𝘭𝘪𝘯𝘦 𝘛𝘳𝘦𝘢𝘵𝘮𝘦𝘯𝘵 𝘪𝘯 𝘌𝘎𝘍𝘙 𝘌𝘹𝘰𝘯 20 𝘐𝘯𝘴𝘦𝘳𝘵𝘪𝘰𝘯-𝘮𝘶𝘵𝘢𝘵𝘦𝘥 𝘈𝘥𝘷𝘢𝘯𝘤𝘦𝘥 𝘕𝘰𝘯-𝘴𝘮𝘢𝘭𝘭 𝘊𝘦𝘭𝘭 𝘓𝘶𝘯𝘨 𝘊𝘢𝘯𝘤𝘦𝘳 (𝘕𝘚𝘊𝘓𝘊): 𝘗𝘳𝘪𝘮𝘢𝘳𝘺 𝘙𝘦𝘴𝘶𝘭𝘵𝘴 𝘍𝘳𝘰𝘮 𝘗𝘈𝘗𝘐𝘓𝘓𝘖𝘕, 𝘢 𝘙𝘢𝘯𝘥𝘰𝘮𝘪𝘻𝘦𝘥 𝘗𝘩𝘢𝘴𝘦 3 𝘎𝘭𝘰𝘣𝘢𝘭 𝘚𝘵𝘶𝘥𝘺
• 𝘓𝘉𝘈4 - 𝘙𝘢𝘯𝘥𝘰𝘮𝘪𝘻𝘦𝘥 𝘗𝘩𝘢𝘴𝘦 3 𝘚𝘵𝘶𝘥𝘺 𝘰𝘧 𝘍𝘪𝘳𝘴𝘵-𝘭𝘪𝘯𝘦 𝘚𝘦𝘭𝘱𝘦𝘳𝘤𝘢𝘵𝘪𝘯𝘪𝘣 𝘷𝘦𝘳𝘴𝘶𝘴 𝘊𝘩𝘦𝘮𝘰𝘵𝘩𝘦𝘳𝘢𝘱𝘺 𝘢𝘯𝘥 𝘗𝘦𝘮𝘣𝘳𝘰𝘭𝘪𝘻𝘶𝘮𝘢𝘣 𝘪𝘯 𝘙𝘌𝘛 𝘍𝘶𝘴𝘪𝘰𝘯-𝘱𝘰𝘴𝘪𝘵𝘪𝘷𝘦 𝘕𝘚𝘊𝘓𝘊
• 𝘓𝘉𝘈2 - 𝘈𝘓𝘐𝘕𝘈: 𝘦𝘧𝘧𝘪𝘤𝘢𝘤𝘺 𝘢𝘯𝘥 𝘴𝘢𝘧𝘦𝘵𝘺 𝘰𝘧 𝘢𝘥𝘫𝘶𝘷𝘢𝘯𝘵 𝘢𝘭𝘦𝘤𝘵𝘪𝘯𝘪𝘣 𝘷𝘦𝘳𝘴𝘶𝘴 𝘤𝘩𝘦𝘮𝘰𝘵𝘩𝘦𝘳𝘢𝘱𝘺 𝘪𝘯 𝘱𝘢𝘵𝘪𝘦𝘯𝘵𝘴 𝘸𝘪𝘵𝘩 𝘦𝘢𝘳𝘭𝘺-𝘴𝘵𝘢𝘨𝘦 𝘈𝘓𝘒+ 𝘯𝘰𝘯-𝘴𝘮𝘢𝘭𝘭 𝘤𝘦𝘭𝘭 𝘭𝘶𝘯𝘨 𝘤𝘢𝘯𝘤𝘦𝘳 (𝘕𝘚𝘊𝘓𝘊)
• 1315𝘔𝘖 - 𝘋𝘶𝘳𝘢𝘣𝘭𝘦 𝘦𝘧𝘧𝘪𝘤𝘢𝘤𝘺 𝘰𝘧 𝘻𝘦𝘯𝘰𝘤𝘶𝘵𝘶𝘻𝘶𝘮𝘢𝘣, 𝘢 𝘏𝘌𝘙2 𝘹 𝘏𝘌𝘙3 𝘣𝘪𝘴𝘱𝘦𝘤𝘪𝘧𝘪𝘤 𝘢𝘯𝘵𝘪𝘣𝘰𝘥𝘺, 𝘪𝘯 𝘢𝘥𝘷𝘢𝘯𝘤𝘦𝘥 𝘕𝘙𝘎1 𝘧𝘶𝘴𝘪𝘰𝘯-𝘱𝘰𝘴𝘪𝘵𝘪𝘷𝘦 (𝘕𝘙𝘎1+) 𝘯𝘰𝘯-𝘴𝘮𝘢𝘭𝘭 𝘤𝘦𝘭𝘭 𝘭𝘶𝘯𝘨 𝘤𝘢𝘯𝘤𝘦𝘳 (𝘕𝘚𝘊𝘓𝘊)
• 𝘓𝘉𝘈6 - 𝘌𝘝-302/𝘒𝘌𝘠𝘕𝘖𝘛𝘌-𝘈39: 𝘖𝘱𝘦𝘯-𝘓𝘢𝘣𝘦𝘭, 𝘙𝘢𝘯𝘥𝘰𝘮𝘪𝘻𝘦𝘥 𝘗𝘩𝘢𝘴𝘦 3 𝘚𝘵𝘶𝘥𝘺 𝘰𝘧 𝘌𝘯𝘧𝘰𝘳𝘵𝘶𝘮𝘢𝘣 𝘝𝘦𝘥𝘰𝘵𝘪𝘯 𝘪𝘯 𝘊𝘰𝘮𝘣𝘪𝘯𝘢𝘵𝘪𝘰𝘯 𝘸𝘪𝘵𝘩 𝘗𝘦𝘮𝘣𝘳𝘰𝘭𝘪𝘻𝘶𝘮𝘢𝘣 (𝘌𝘝+𝘗) 𝘝𝘴 𝘊𝘩𝘦𝘮𝘰𝘵𝘩𝘦𝘳𝘢𝘱𝘺 (𝘊𝘩𝘦𝘮𝘰) 𝘪𝘯 𝘗𝘳𝘦𝘷𝘪𝘰𝘶𝘴𝘭𝘺 𝘜𝘯𝘵𝘳𝘦𝘢𝘵𝘦𝘥 𝘓𝘰𝘤𝘢𝘭𝘭𝘺 𝘈𝘥𝘷𝘢𝘯𝘤𝘦𝘥 𝘔𝘦𝘵𝘢𝘴𝘵𝘢𝘵𝘪𝘤 𝘜𝘳𝘰𝘵𝘩𝘦𝘭𝘪𝘢𝘭 𝘊𝘢𝘳𝘤𝘪𝘯𝘰𝘮𝘢 (𝘭𝘢/𝘮𝘜𝘊)
• 𝘓𝘉𝘈7 - 𝘕𝘪𝘷𝘰𝘭𝘶𝘮𝘢𝘣 𝘱𝘭𝘶𝘴 𝘨𝘦𝘮𝘤𝘪𝘵𝘢𝘣𝘪𝘯𝘦-𝘤𝘪𝘴𝘱𝘭𝘢𝘵𝘪𝘯 𝘷𝘦𝘳𝘴𝘶𝘴 𝘨𝘦𝘮𝘤𝘪𝘵𝘢𝘣𝘪𝘯𝘦-𝘤𝘪𝘴𝘱𝘭𝘢𝘵𝘪𝘯 𝘢𝘭𝘰𝘯𝘦 𝘧𝘰𝘳 𝘱𝘳𝘦𝘷𝘪𝘰𝘶𝘴𝘭𝘺 𝘶𝘯𝘵𝘳𝘦𝘢𝘵𝘦𝘥 𝘶𝘯𝘳𝘦𝘴𝘦𝘤𝘵𝘢𝘣𝘭𝘦 𝘰𝘳 𝘮𝘦𝘵𝘢𝘴𝘵𝘢𝘵𝘪𝘤 𝘶𝘳𝘰𝘵𝘩𝘦𝘭𝘪𝘢𝘭 𝘤𝘢𝘳𝘤𝘪𝘯𝘰𝘮𝘢: 𝘳𝘦𝘴𝘶𝘭𝘵𝘴 𝘧𝘳𝘰𝘮 𝘵𝘩𝘦 𝘱𝘩𝘢𝘴𝘦 3 𝘊𝘩𝘦𝘤𝘬𝘔𝘢𝘵𝘦 901 𝘵𝘳𝘪𝘢𝘭
• 652𝘖 - 𝘗𝘳𝘦𝘭𝘪𝘮𝘪𝘯𝘢𝘳𝘺 𝘤𝘭𝘪𝘯𝘪𝘤𝘢𝘭 𝘢𝘤𝘵𝘪𝘷𝘪𝘵𝘺 𝘰𝘧 𝘙𝘔𝘊-6236, 𝘢 𝘧𝘪𝘳𝘴𝘵-𝘪𝘯-𝘤𝘭𝘢𝘴𝘴, 𝘙𝘈𝘚-𝘴𝘦𝘭𝘦𝘤𝘵𝘪𝘷𝘦, 𝘵𝘳𝘪-𝘤𝘰𝘮𝘱𝘭𝘦𝘹 𝘙𝘈𝘚-𝘔𝘜𝘓𝘛𝘐(𝘖𝘕) 𝘪𝘯𝘩𝘪𝘣𝘪𝘵𝘰𝘳 𝘪𝘯 𝘱𝘢𝘵𝘪𝘦𝘯𝘵𝘴 𝘸𝘪𝘵𝘩 𝘒𝘙𝘈𝘚 𝘮𝘶𝘵𝘢𝘯𝘵 𝘱𝘢𝘯𝘤𝘳𝘦𝘢𝘵𝘪𝘤 𝘥𝘶𝘤𝘵𝘢𝘭 𝘢𝘥𝘦𝘯𝘰𝘤𝘢𝘳𝘤𝘪𝘯𝘰𝘮𝘢 (𝘗𝘋𝘈𝘊) 𝘢𝘯𝘥 𝘯𝘰𝘯-𝘴𝘮𝘢𝘭𝘭 𝘤𝘦𝘭𝘭 𝘭𝘶𝘯𝘨 𝘤𝘢𝘯𝘤𝘦𝘳 (𝘕𝘚𝘊𝘓𝘊)
• How to implement local LoE1A HRD testing: experience of a center of excellence - Carsten Denkert (Marburg, Germany)
• LBA14 - Amivantamab Plus Lazertinib vsOsimertinib as First-line Treatment in Patients With EGFR-mutated, Advanced
  Non-small Cell Lung Cancer (NSCLC): Primary Results From MARIPOSA, a Phase 3,
  Global, Randomized, Controlled Trial
• LBA15 - Amivantamab Plus Chemotherapy(With or Without Lazertinib) vs Chemotherapy in EGFR-mutated Advanced NSCLC
  After Progression on Osimertinib: MARIPOSA-2, a Phase 3, Global, Randomized,
  Controlled Trial
• Artificial intelligence in prognostication - chaired by Sanjay Aneja (New Heaven, United States of America) and Anne Vincent-Salomon (Paris, France)