Conference Report: European Society for Medical Oncology Congress 2022

Abstract

The European Society of Medical Oncology took place in Paris Convention Centre, Paris, France on 9th −13th September 2022 and was attended by more than 28,000 delegates, 23,000 of which were in person and 5000 online. This was the first on-site ESMO congress after the COVID-19 pandemic. This report focuses on a selection of talks delivered at the conference. There was a vast collection of interesting talks, nevertheless, I attended talks that focused on rare cancers.

Day 1

ESMO Congress 2022 opening session

Day one started with a warm welcome from the ESMO President, Solange Peters (Centre Hospitalier Universitaire, Vaudois (CHUV), Lausanne, Switzerland). Her speech focused on the importance of sustainability in oncology, and the oncology community’s responsibility to safeguard patients’ ability to access high-quality care, tomorrow. ESMO aims to contribute to the overall sustainability of the healthcare system by nurturing the professional development of oncologists and supporting them in their daily practice.

Ultra-rare sarcoma: navigating an endless sea

One of the first sessions started with Inga-Marie Schaefer, from the Brigham and Women’s Hospital and Harvard Medical School, Massachusetts, USA.

Sarcomas are a rare group of cancers that make up 1% of all cancers, which means pathologic diagnosis can be very challenging. Dr Schaefer pointed out that diagnostic work-up of sarcomas relies on a multifaceted approach which is based on histomorphology with immunohistochemistry and genetic testing. Careful integration of clinical information and radiologic findings is required for accurate diagnosis. She also mentioned that genetic abnormalities can be tumour-specific or non-specific, and molecular testing can enable the discovery of new entities that are defined by recurrent genomic events and refine classification systems.

The second speaker of the session was Silvia Stacchiotti from Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, whose session focused on new drugs for ultra-rare sarcomas, and challenges in finding the optimal treatment for each of these rare tumor types. Following Silvia Stacchiotti’s talk, Hugh Leonard from The EHE Rare Cancer Charity talked about advocating for patients with ultra-rare cancers. Epithelioid Haemangioendothelioma (EHE) is an ultra-rare sarcoma, and there are around 25 cases diagnosed per year in the UK. 90% of EHEs are caused by a single gene translocation (WWTR1 (TAZ)-CAMTA1). Hugh Leonard highlighted the current EHE research, which involved gene translocations and resultant fusion proteins identification. Furthermore, fusion protein transcription is beginning to be understood better as a result of this research. According to the study, multiple high-quality EHE model systems were developed or are currently in progress and in-vitro models, such as mouse pluripotent stem cells, as well as PDX, zebrafish and GEM models, are used in EHE research. There are also multiple projects looking at the biology of EHE at cellular and subcellular levels. Biomarkers, hormones, miRNA, and negative regulators and agents of the fusion protein are being identified as a result.

Adjuvant and perioperative therapy for non-colorectal gastrointestinal cancers: latest status

This exciting session started with Elizabeth Smyth’s (Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK) talk on gastroesophageal cancer. In her talk, she covered operable gastroesophageal cancer and the current standards of care for squamous esophageal cancer, gastroesophageal junction adenocarcinoma and gastric adenocarcinoma. Jennifer Knox from Princess Margaret Cancer Centre (Toronto, Canada) discussed the latest status of adjuvant and perioperative therapy for hepatobiliary cancers. She highlighted that no adjuvant approach exists outside trials currently, and many promising studies report evaluating IO or IO/VEGF combination. Biomarker discovery is planned to be added to the current studies and innovative peri-operative strategies are underway. She concluded that, a multidisciplinary approach is key in all hepatobiliary cancers.

The session ended with Thierry Conroy (Institut de Cancérologie de Lorraine, Nancy, France) covering adjuvant and perioperative treatment for pancreatic cancer. She argued that patients with borderline resectable pancreatic cancer should receive induction therapy and completion of all cycles of adjuvant chemotherapy is a significant predictive factor for overall survival. Resectable pancreatic ductal adenocarcinoma (PDAC) is a systemic disease and, therefore, neoadjuvant treatment is a logical approach, however, the optimal treatment strategy has yet to be defined. Dr Conroy concluded that neoadjuvant therapy in resectable pancreatic cancer still needs validation through high quality fully published randomized studies.

Day 2

Management of adrenocortical carcinoma

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer type that is asymptomatic at presentation, however, has a high rate of metastatic disease at the time of diagnosis. The treatment of ACC requires a multi-disciplinary approach and, in this session, various approaches to adrenocortical carcinoma were presented.

The first presentation was from Andrea Frilling from Imperial College London, UK who highlighted various surgical techniques currently available; such ascomplete en bloc resection with peri-tumoural/peri-adrenal retroperitoneal, open surgery, laparoscopic/robotic adrenalectomy for tumors smaller than 6 cm, locoregional lymphadenectomy, and perioperative hydrocortisone replacement. The benefits and challenges of each surgical option were also discussed in this session. Dr Frilling concluded that adjuvant radiotherapy is potentially able to reduce the risk of local recurrence, however, does not prevent distant metastases. Another important topic discussed at the session was the use of systematic therapies in the management of ACC. Eric Baudin (Institut Gustave Roussy, Villejuif, France) highlighted the current understanding of the efficacy of mitotane and platine-based chemotherapy, as well as the progress in prognostic stratification.

Last but not least, Matthias Kroiss from the Ludwig Maximilians University of Munich, Germany, also discussed the potential role of immunotherapy in the management of ACC. The results of clinical trials investigating the use of cabozantinib monotherapy were presented, and Dr Kroiss concluded that the results of immune checkpoint inhibitors with a response rate of ∼14% were plausible as a second-line treatment where available and novel approaches (combination with TKI, such as cabozantinib, vaccination) in ACC is a reasonable approach.

Proffered paper session 1: Genitourinary tumours, non-prostate

This exciting session started with Axel Bex’s (The Royal Free London NHS Foundation Trust, University College London, UK & The Netherlands Cancer Institute, Amsterdam, Netherlands) presentation on IMmotion010, which is a Phase III, multicentre, randomised, placebo-controlled, double-blinded trial, that evaluated atezolizumab (anti-PD-L1) monotherapy as adjuvant therapy in patients with RCC and increased risk of recurrence after resection. The standard of care for loco-regional RCC is nephrectomy, but many patients experience recurrence. This study found that the results that atezolizumab as adjuvant therapy after resection for patients with renal cell cancer with an increased risk of recurrence did not improve clinical outcomes compared to a placebo. According to the trial, atezolizumab was tolerated by the patients, and safety results were consistent with the known safety profile of atezolizumab. Subgroup analysis suggested further evaluation of sarcomatoid and high-expression PD-L1 populations is necessary. Furthermore, biomarker analyses are currently ongoing to identify patients who may benefit from adjuvant atezolizumab. He concluded that further studies are needed to clarify the role of immunotherapy in the adjuvant setting for renal cell carcinoma.

Another phase III randomized study, comparing perioperative nivolumab (nivo) versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER, ECOG-ACRIN EA8143) was presented by Mohamad E. Allaf (Johns Hopkins University, Maryland, USA). According to the trial, perioperative nivolumab did not improve recurrence-free survival in patients with renal cell carcinoma at high risk for recurrence. Furthermore, Dr Allaf reported that adverse events in the surgery + nivolumab arm were consistent with the toxicity profile in other nivolumab trials. Ongoing radiomic, pathomic and other biomarker analyses within this trial may help shape the design of future neoadjuvant renal cell carcinoma trials.

Proffered paper session 1: Melanoma and other skin tumours

I attended another proffered paper session on day 2, focusing on melanoma and other skin tumors. This session started with Dirk Schadendorf’s (University Hospital Essen Westdeutsches Tumorzentrum, Essen, Germany) presentation on the findings of a randomized, double-blind multi-centre phase II DeCOG trial on adjuvant nivolumab (NIVO) alone or in combination with ipilimumab (IPI) versus placebo in stage IV melanoma with no evidence of disease (NED) - overall survival results of IMMUNED. According to Prof Schadendorf, this was the first prospective randomized placebo-controlled trial in stage IV melanoma with NED. The results of the trial showed a median follow-up of 49.2 months, NIVO plus IPI and NIVO continue to show a clinically and statistically significant improvement in RFS versus placebo for patients with fully resected or irradiated stage IV melanoma at a high risk of recurrence.

Reinhard Dummer from Universitätsspital Zürich, Switzerland highlighted the findings of the final 5-year results of phase II, multicenter, randomized, open-label trial of talimogene laherparepvec (T-VEC) neoadjuvant treatment plus surgery versus immediate surgery in patients with resectable stage IIIB-IVM1a melanoma. The risk of recurrence after resection remains high in patients with advanced melanoma. Neoadjuvant therapies before surgery have been shown to reduce recurrence risks, shrink tumors, and potentially improve long-term outcomes. In this final readout of the largest randomized neoadjuvant trial for an oncolytic virus in advanced melanoma, Prof Dummer reported durable improvements in recurrence-free survival, event-free survival, and overall survival at 5 years with neoadjuvant T-VEC + surgery versus standard surgery. The trial showed that no new safety signals were observed. These results also suggest that an intratumorally administered oncolytic agent can elicit a meaningful long-term systemic effect and support neoadjuvant T-VEC and surgery in advanced resectable melanoma.

The next presentation highlighted the findings of the phase II study of multiple LXH254 drug combinations in patients with unresectable/metastatic, BRAF V600- or NRAS-mutant melanoma, which was presented by Celeste Lebbe (Université Paris Cité, Paris, France). The mitogen-activated protein kinase pathway is often dysregulated in melanoma. Therefore, the trial explored LXH254 combined with LTT462, trametinib, or ribociclib in previously treated, BRAF V600 or NRAS-mutant melanoma. The results of the trial showed that naporafenib combined with rineterkib, trametinib, or ribociclib exhibited tolerable safety profiles. It also showed promising efficacy in NRAS-mutant, immuno-resistant melanoma, with an ORR of 21% and a DCR of 61%, especially with the combination of naporafenib with rineterkib or trametinib. Furthermore, steady-state pharmacokinetic exposures for rineterkib, trametinib, and ribociclib combinations with naporafenib were observed within the same ranges as when administered as a single agent, indicating no apparent drug-to-drug interactions with naporafenib. According to the study, these results warrant further investigation of naporafenib combinations in immuno-resistant, NRAS-mutant melanoma. The final trial on the initiation of phase III, a randomized, open-label PIVOT IO 001 study, evaluated bempegaldesleukin (BEMPEG) + nivolumab (NIVO) vs nivolumab in advanced melanoma was presented by Adi Diab (The University of Texas MD Anderson Cancer Center, Houston, Texas, US). The trial aimed to report the efficacy and safety of PIVOT IO 001. The results of this study showed that BEMPEG + NIVO did not improve objective response rate, progression-free survival, or overall survival rate versus NIVO alone in patients with treatment-naive advanced melanoma in the phase 3 PIVOT IO 001 trial. According to Dr Diab, the trial was discontinued, and no further overall survival analyses will be conducted. A higher incidence of adverse events was observed with BEMPEG and the rash was more common in patients receiving BEMPEG + NIVO versus NIVO monotherapy. A robust increase in absolute lymphocyte count following BEMPEG + NIVO indicated that BEMPEG was active in mediating immunomodulatory pharmacodynamic effects.

Day 3

Proffered paper session: Genitourinary tumours, prostate

In one of the first sessions of day 3, there was another session on genitourinary (GU) tumors, however, unlike the first session on this subject, the focus was on the prostate. The first study was presented by Gerhardt Attard (University College London Cancer Institute, London’s Global University, London, UK) on the first combined analysis of metastatic patients starting androgen deprivation therapy (ADT) and randomised in the abiraterone acetate and prednisolone (AAP) or enzalutamide (ENZ) and AAP Phase III trials from the STAMPEDE platform protocol. According to the study, abiraterone acetate and prednisolone or enzalutamide added to ADT improve outcomes for mHSPC, and combining ENZ & AAP may improve rPFS in mCRPC but no discernible improvement in OS3, as the benefit in mHSPC is uncertain. The results of the study showed that ENZ and AAP should not be combined for mHSPC and clinically important improvements in overall survival when AAP is added to ADT are maintained at 7 years.

The next trial of the session was the clinical qualification of transcriptome signatures for advanced prostate cancer starting androgen deprivation therapy with or without abiraterone acetate and prednisolone: an ancillary study of the STAMPEDE trial, which was presented by Marina Parry (University College London Cancer Institute, London, UK). The study highlighted the identification of the consistent effect of the addition of abiraterone acetate and prednisolone on overall survival in the combined cohort. The benefit of adding AAP to ADT was greater in patients with higher GC-risk tumours, all four primary signatures were prognostic in M0 for MFS, and exploratory analysis reveals different signatures are prognostic in M1 and M0.

In the following presentation, Fred Saad (Université de Montreal, Montreal, Canada) reported the biomarker analysis from the primary analysis and updated overall survival and safety data from a planned overall survival interim analysis from the Phase III PROpel trial of abiraterone and olaparib versus abiraterone and placebo as first-line therapy for patients with metastatic castration-resistant prostate cancer. At primary analysis, abiraterone + olaparib demonstrated a significant improvement in rPFS. Furthermore, a clinically meaningful improvement of >8 months in average rPFS was observed in the intention-to-treat population, and in the assessed biomarker subgroup analyses, there was an improvement of at least 5 months. The trial also reported that updated results at DCO2 were consistent with the results at DCO1 and showed a continuing trend towards an overall survival benefit in the intention-to-treat population. The safety and tolerability results were generally consistent with the primary analysis and the known profiles for abiraterone and Olaparib.

State-of-the-art: Diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and complex cancer types that present many clinical challenges. This session covered topics such as what oncologists need to know about GEP-NET before commencing therapy, and treatment of small intestinal NETs and pancreatic NETs.

The session started with Eva Tiensuu Janson’s (University Hospital Uppsala, Sweden) presentation on “What oncologists need to know about GEP-NET before commencing therapy”. She highlighted the importance of knowing the origin of the primary tumor, and histopathology and tumor grade according to WHO when selecting the correct therapy option. She pointed out that hormone-related symptoms can be fatal and should be managed swiftly. Furthermore, tumor spread, and somatostatin receptor status must be clarified. WHO grade in pancreatic NETs can be defined by genetic analyses, which can help in making an accurate treatment decision.

Marianne Pavel from Friedrich-Alexander Universität Erlangen- Nürnberg Erlangen, Germany, highlighted the diagnosis and treatment of small intestinal NETs in this session. Multiple comorbidities may be observed in patients with advanced SI NET, therefore, an MDT approach is needed due to the complexity of the disease. She presented that the presence of carcinoid syndrome requires an upfront antisecretory therapy. Somatostatin analogues (SSA) are 1st line antiproliferative therapy in advanced indolent NET, and peptide receptor radionuclide therapy (PRRT) is recommended as 2nd line therapy in patients. She also mentioned that emerging therapies include tyrosine kinase inhibitors and targeted alpha emitter therapy as well as CPI in combination with other compounds.

Nicola Fazio (Instituto Europeo di Oncologia, Milan, Italy) who is an Editorial Board Member of Rare Tumors, presented his session on the treatment of pancreatic NET in this educational session. He highlighted the systemic therapies for advanced panNETs which include everolimus, sunitinib, SSAs (Lanreotide, Octreotide), PRRT (177Lutethium-DOTATATE) and chemotherapy (mainly alkylating-based), presenting the results of various studies involving these treatment methods. He concluded that the clinical management of each patient with advanced panNET should be discussed within a NEN-dedicated multidisciplinary team from the beginning.

Rare head and neck cancer

This educational session started with Keith D. Hunter’s (University of Liverpool, Liverpool, UK) presentation on the pathology of salivary gland cancers and sino-nasal cancers. Prof Hunter gave a brief overview of malignant salivary gland tumors and malignant sinonasal tumors. He highlighted the distribution of minor glad tumors, risk stratification and challenges in salivary gland tumor diagnosis. Similarly, Prof Hunter also focused on malignant sinonasal tumors, their classification and the challenges in sinonasal malignancy diagnosis.

Following Prof Hunter’s session, Carla Van Herpen (Radboud University Medical Center, Nijmegen, the Netherlands) presented an overview of the treatment algorithm for recurrent/metastatic salivary gland cancers. Salivary gland cancer (SGC) is a highly heterogeneous disease consisting of 22 subtypes. These cancers make up 6.5% of all head and neck cancers in Europe. Approximately 60–70% of SGC patients develop recurrent or metastatic disease. The average overall survival is 15 months and there is a large variation in overall survival. In several of the subtypes, novel systemic treatment strategies can be used, such as chemotherapy, hormonal therapy, targeted therapy and immunotherapy. Furthermore, immunohistochemistry and genomic profiling can identify targeted therapy options. Prof Van Harpen concluded that this approach can significantly alter the prognosis of salivary gland cancer patients.

The final presentation of the session was from Paolo Bossi (Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy). Dr Bossi highlighted the contemporary approach to the multidisciplinary management of sino-nasal cancer. There are uncertainties about the management of sinonasal cancers in terms of surgical management, sequences of treatment, use of chemotherapy and dose fractionation. He pointed out the importance of precision medicine and how a multidisciplinary approach is the key approach to the management of sino-nasal cancer.

Day 4

Mini oral session: neuroendocrine tumors and endocrine tumors

On the last day of the ESMO Congress, I attended a mini-oral session that covered multiple trials and studies on neuroendocrine and endocrine tumors. The first short presentation was from Christine Dierks (University of Halle-Wittenberg, Halle, Germany) on Phase II ATLEP trial: Results for lenvatinib/pembrolizumab in metastasized anaplastic and poorly differentiated thyroid carcinoma. The trial showed that a combination of lenvatinib and pembrolizumab is observed to be safe and effective in patients with anaplastic thyroid carcinoma and poorly differentiated thyroid carcinoma and induces high response rates including long-lasting remissions.

Christelle de la Fouchardiere from Centre Léon Bérard, Lyon, France, presented their findings on clinical characteristics and outcomes of BRAF-mutated anaplastic thyroid carcinoma under BRAF inhibitors and chemotherapy in real-life practice - a multicentric retrospective study of the French ENDOCAN TUTHYREF network. According to the study, the results confirmed the clinical benefit of BRAF inhibitors in BRAF-mutated ATC in a real-life population. BRAF inhibitors improved overall survival, which represents a meaningful treatment option for this aggressive cancer.

The third study of the session was on the emergence of clonal hematopoiesis after peptide receptor radionuclide therapy for neuroendocrine tumors. This study was presented by Rachel El Ferkh from Institut Gustave Roussy, Cedex, France. The trial aimed to assess the effects of peptide receptor radionuclide therapy on the development of therapy-related myeloid neoplasms. According to the results of the study, therapy-related myeloid neoplasms after peptide receptor radionuclide therapy are not so rare and had an unfavorable outcome. Patients with NET have a very high incidence of clonal hematopoiesis. Furthermore, patients exposed to PRRT seem to have more clonal hematopoiesis, especially PPM1D and TP53 mutations, suggesting a potential clonal selection of this treatment.

Extra-pulmonary small cell carcinomas (EPSCC) are aggressive neuroendocrine tumors that are clinicopathologically distinct from small cell lung cancer (SCLC). According to the study on the comparative expression of driver transcription factors in extra-pulmonary small cell carcinoma that was presented by Stephen Liu (Huntsman Cancer Institute, Salt Lake City, US) differential expression of key lineage-defining transcription factors in EPSCCs from various anatomic sites that looked distinct from SCLC. EPSCC and SCLC overall survival were similarly associated with transcription factor expression, suggesting the underlying biology of SCLC and EPSCC subtypes might predict comparable therapeutic vulnerabilities.

The next presentation was from Halfdan Sorbye, (Haukeland Universitetssykehus, Bergen, Norway) on the mutation spectrum in liquid versus solid biopsies from advanced digestive neuroendocrine carcinoma patients. Digestive neuroendocrine carcinomas (NEC) are currently defined by the presence of a poorly differentiated neuroendocrine phenotype and a high proliferation rate. Most digestive NECs are diagnosed with metastatic disease with survival of less than 1 year if medically treated. This trial found liquid biopsy analyses to be an applicable alternative treatment to solid biopsies in digestive NEC patients. It was concluded that liquid biopsies could be potentially used for biomarker assessment in clinical trials for these patients.

The final presentation of the session came from Eric Baudin (Institut Gustave Roussy, Villejuif, France). In this phase 1/2 SPENCER study, EO2401 (EO) therapeutic vaccine for patients with adrenocortical carcinoma (ACC) and malignant pheochromocytoma/paraganglioma (MPP) was evaluated. EO was designed to activate memory T cells cross-reacting with tumor-associated antigens (TAAs). EO includes microbial-derived synthetically produced HLA-A2 restricted peptides with mimicry to TAAs upregulated in ACC/MPP and CD4 peptide UCP2. According to the results of this trial, EO2401 was well tolerated and generated immune responses correlating with efficacy. Efficacy was seen in the ACC group defined post-hoc by clinical parameters.

Proffered paper session: neuroendocrine tumors and endocrine tumours

This is the second proffered paper session on NETs and endocrine tumors chaired on the last day of the congress. In this session, more interesting studies and trials were covered. The first speaker of the session was Ramon Salazar from the Catalan Institute of Oncology, Barcelona, Spain. Dr Salazar presented the results of the randomized open-label phase III study comparing the efficacy and safety of everolimus followed by chemotherapy with streptozotocin-5FU upon progression or the reverse sequence, in advanced progressive panNETs, the SEQTOR study. According to the results of the study, both sequential strategies showed similar efficacy, with no significant differences in progression-free survival rate to 1st treatment. STZ-5FU assigned as the 1st treatment achieved a statistically significantly higher objective response rate than everolimus, suggesting STZ-5FU should be the 1st option when tumor shrinkage is a priority. They reported that the differences in safety profile may also inform treatment choice for selected patients.

The second presenter of this interesting session was once again Eric Baudin. He reported the findings of the first multicentric randomized phase II trial investigating the antitumor efficacy of peptide receptor radionuclide therapy with 177Lutetium –DOTA-Octreotate in unresectable progressive neuroendocrine pancreatic tumor. He highlighted that no randomized trial has investigated the role of peptide receptor radionuclide therapy in advanced pancreatic neuroendocrine tumor patients. The results of the trial showed that 177Lu-DOTATATE is associated with 80% 12-month progression-free survival in an aggressive advanced pancreatic neuroendocrine tumor population no new safety concern was found. It also showed the highest level of evidence of the antitumor role of 177Lu-DOTATATE ever reached in this very rare cancer.

A further randomized, double-blind, placebo-controlled, multicenter phase III clinical trial (DIRECTION) on donafenib in locally advanced/metastatic, radioactive iodine-refractory, differentiated thyroid cancer was presented by Yansong Lin (Peking Union Medical College Hospital, Beijing, China). Donafenib was reported to have shown potent efficacy and a well-tolerated safety profile in patients with progressive locally advanced/metastatic radioactive iodine-refractory differentiated thyroid cancer in a phase II study. The aim of the DIRECTION study was to evaluate the efficacy and safety of donafenib and initiated when there were no available tyrosine kinase inhibitors for Chinese radioactive iodine-refractory, differentiated thyroid cancer patients. The results of the trial showed that the efficacy and safety of donafenib are well-balanced, suggesting its potential to be an alternative for patients with progressive RAIR-DTC.

In the final presentation of the session, Jaume Capdevila Castillon (Vall Hebron University Hospital, Vall Hebron Institute of Oncology, Barcelona, Spain) the findings of the DUTHY (GETNE-T1812) trial on durvalumab plus tremelimumab for the treatment of patients with progressive, refractory advanced thyroid carcinoma was highlighted. Thyroid cancer is one the most common endocrine malignancy, although it is a rare tumor in advanced stages. Targeting PD-L1 has proven limited efficacy in advanced thyroid cancer patients. The trial showed that the combination of durvalumab and tremelimumab was tolerable in thyroid cancer, and showed promising activity in heavily pretreated advanced DTC and MTC.

ESMO Congress 2023 will be taking place in Madrid, Spain at the IFEMA Madrid on 20–24 October 2023.

ORCID iD

Sevda Dogan https://orcid.org/0000-0003-2720-8752