European Society For Medical Oncology Research Articles

The impact of COVID-19 on oncology professionals—one year on: lessons learned from the ESMO Resilience Task Force survey series

BackgroundCOVID-19 has had a significant impact on the well-being and job performance of oncology professionals globally. The European Society for Medical Oncology (ESMO) Resilience Task Force collaboration set out to investigate and monitor well-being since COVID-19 in relation to work, lifestyle and support factors in oncology professionals 1 year on since the start of the pandemic.MethodsAn online, anonymous survey was conducted in February/March 2021 (Survey III). Key outcome variables included risk of poor well-being or distress (expanded Well-Being Index), feeling burnout (single item from expanded Well-Being Index), and job performance since COVID-19. Longitudinal analysis of responses to the series of three surveys since COVID-19 was carried out, and responses to job demands and resources questions were interrogated. SPSS V.26.0/V.27.0 and GraphPad Prism V9.0 were used for statistical analyses.ResultsResponses from 1269 participants from 104 countries were analysed in Survey III: 55% (n = 699/1269) female, 54% (n = 686/1269) >40 years, and 69% (n = 852/1230) of white ethnicity. There continues to be an increased risk of poor well-being or distress (n = 464/1169, 40%) and feeling burnout (n = 660/1169, 57%) compared with Survey I (25% and 38% respectively, P < 0.0001), despite improved job performance. Compared with the initial period of the pandemic, more participants report feeling overwhelmed with workload (45% versus 29%, P < 0.0001). There remain concerns about the negative impact of the pandemic on career development/training (43%), job security (37%). and international fellowship opportunities (76%). Alarmingly, 25% (n = 266/1086) are considering changing their future career with 38% (n = 100/266) contemplating leaving the profession.ConclusionOncology professionals continue to face increased job demands. There is now significant concern regarding potential attrition in the oncology workforce. National and international stakeholders must act immediately and work closely with oncology professionals to draw up future-proof recovery plans.

Impact of the COVID-19 Pandemic on Patients with Gastrointestinal Cancer Undergoing Active Cancer Treatment in an Ambulatory Therapy Center: The Patients' Perspective.

Background: The mortality risk increases greatly in patients with cancer if they are infected with severe acute respiratory syndrome coronavirus 2. The new American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) guidelines for the COVID-19 pandemic suggested modifications to the standards of care to reduce harm from treatment. However, it is unclear whether these changes suit the wishes of patients. Methods: We conducted a survey of patients with gastrointestinal cancer who were undergoing active chemotherapy in our ambulatory therapy center between 17 August and 11 September 2020. The survey comprised 18 questions on five topics: patient characteristics, lifestyle changes, disturbance in their psychological health, thoughts on the cancer treatment, and infection control in the hospital. Results: Among the 63 patients who received the questionnaire, 61 participated in the study. The COVID-19 pandemic has led to changes in their lifestyles and substantially impacted their psychological wellbeing. The incidence of anxiety and insomnia has considerably increased during the pandemic. However, female patients and patients aged 70 years or older reported no notable differences. There was no significant difference in the responses to the questions regarding thoughts on the cancer treatment. Conclusion: Our study revealed that the COVID-19 pandemic has substantially impacted patients’ lifestyles and psychological wellbeing. However, most patients preferred to continue their usual treatment without any change to their treatment plan. It is important to involve the patient in the decision-making process when formulating treatment goals.

Efficacy and Safety Associated With Immune Checkpoint Inhibitors in Unresectable Hepatocellular Carcinoma

Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research. To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC. PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020. From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC. The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model. The main outcomes were OS, PFS, ORR, and TRAEs. Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04). This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.

PD-1 inhibitors versus chemotherapy as second-line treatment for advanced esophageal squamous cell carcinoma: a meta-analysis

BackgroundAim to establish the inhibitors of programmed cell death protein 1 (PD-1) as second-line therapy for advanced esophageal squamous cell carcinoma (ESCC).MethodsPublished clinical trials in the PubMed, Medline, Embase databases on PD-1 inhibitors for the treatment of ESCC were searched, along with an additional search on abstracts from the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) from inception to September 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs) were synthesized using STATA.ResultsA total of 1970 patients (PD-1 inhibitors: 987; chemotherapy: 983) were enrolled in five randomized controlled trials. Compared with conventional chemotherapy, second-line PD-1 inhibitors significantly improved the OS (hazard ratio [HR] = 0.73, 95% confidence interval [CI]: 0.66–0.81; P < 0.001) and ORR (relative risk [RR] = 1.89, 95% CI: 1.16–3.05; P = 0.01) of advanced ESCC patients, especially significantly prolonged the OS in the patients with positive programmed death-ligand 1 (PD-L1) status (HR = 0.64, 95% CI: 0.53–0.77; P < 0.001); but did not better PFS (HR = 0.88, 95% CI: 0.68–1.14; P = 0.330) and DCR (RR = 0.89, 95% CI: 0.59–1.37; P = 0.603). Moreover, PD-1 inhibitors were associated with statistically lower incidences of grade 3–5 TRAEs.ConclusionSecond line PD-1 inhibitors significantly improved the OS and ORR of patients with advanced ESCC, especially the OS of those with positive PD-L1 expression, and did not result in significant improvement in PFS and DCR. Compared to chemotherapy, second-line PD-1 inhibitors had superior safety profiles for the treatment of advanced ESCC.

An Update on Thyroid Cancer Trials from the European Society of Medical Oncology (ESMO) 2021 Annual Meeting

Clinical ThyroidologyVol. 33, No. 11 Thyroid CancerAn Update on Thyroid Cancer Trials from the European Society of Medical Oncology (ESMO) 2021 Annual MeetingJochen H. LorchJochen H. LorchDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, U.S.A.Member, International Oncology Thyroid Group (ITOG)Search for more papers by this authorPublished Online:12 Nov 2021https://doi.org/10.1089/ct.2021;33.500-502AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 33Issue 11Nov 2021 InformationCopyright 2021 American Thyroid Association, Inc.To cite this article:Jochen H. Lorch.An Update on Thyroid Cancer Trials from the European Society of Medical Oncology (ESMO) 2021 Annual Meeting.Clinical Thyroidology.Nov 2021.500-502.http://doi.org/10.1089/ct.2021;33.500-502Published in Volume: 33 Issue 11: November 12, 2021PDF download

Genomic Alterations in Head and Neck Squamous Cell Carcinoma: Level of Evidence According to ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)

Development of high-throughput technologies helped to decipher tumor genomic landscapes revealing actionable molecular alterations. We aimed to rank the level of evidence of recurrent actionable molecular alterations in head and neck squamous cell carcinoma (HNSCC) on the basis of the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) to help the clinicians prioritize treatment. We identified actionable alterations in 33 genes. HRAS-activating mutations were ranked in tier IB because of the efficacy of tipifarnib (farnesyltransferase inhibitor) in HRAS-mutated patients with HNSCC (nonrandomized clinical trial). Microsatellite instability (MSI), high tumor mutational burden (TMB), and NTRK fusions were ranked in tier IC because of PD-1 and TRK tyrosine kinase inhibitors tissue-agnostic approvals. CDKN2A-inactivating alterations and EGFR amplification were ranked in tier IIA because of the efficacy of palbociclib (CDK4/6 inhibitor) and afatinib (tyrosine kinase inhibitor) in these respective molecular subgroups in retrospective analyses of clinical trials. Molecular alterations in several genes, including PIK3CA gene, were ranked in tier IIIA because of clinical benefit in other tumor types, whereas molecular alterations in IGF1R and TP53 genes were ranked in tier IVA and tier V, respectively. The most compelling actionable molecular alterations in HNSCC according to ESCAT include HRAS-activating mutations, MSI, high TMB, NTRK fusions, CDKN2A-inactivating alterations, and EGFR amplification.

Efficacy and Safety of Programmed Cell Death 1 Inhibitor Monotherapy Versus Chemotherapy as Second-Line Treatment for Advanced Esophageal Cancer: A Meta-analysis and Systematic Review

PurposeWith programmed cell death 1 (PD-1) inhibitors approved for second-line treatment of advanced esophageal cancer, immunotherapy and chemotherapy have gradually become the main treatments for second-line treatment of patients with advanced esophageal cancer (AEC). This meta-analysis and systematic review were conducted to evaluate the efficacy and safety of PD-1 inhibitors monotherapy versus chemotherapy in second-line treatment of AEC. MethodsEligible randomized controlled trials were searched in PubMed, Embase, and the Cochrane Library and abstracts presented at the American Society of Clinical Oncology or European Society of Medical Oncology were reviewed to assess the efficacy and tolerability of PD-1/programmed cell death ligand 1 (PD-L1) inhibitors relative to chemotherapy for AEC from January 2016 to October 2020. Patients diagnosed with AEC and progressing after first-line therapy were included in this study. Hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) of objective response rate (ORR), and the odds ratios (ORs) of adverse effects (AEs) were calculated. FindingsThe study included 4 randomized controlled trials with 1683 patients. The results indicated that PD-1 inhibitors prolonged the OS (HR = 0.79; 95% CI, 0.71–0.88; P < 0.01) and improved the ORR (RR = 3.00; 95% CI, 2.36–3.82; P = 0.01) but did not improve the PFS (HR = 0.96; 95% CI, 0.76–1.20; P = 0.692) compared with chemotherapy in the second-line treatment of AEC. PD-1 inhibitors alone were associated with a lower incidence of all treatment-related AEs (OR = 0.29; 95% CI, 0.09–0.89; P = 0.03) and grade 3 to 5 treatment-related AEs (OR = 0.26; 95% CI, 0.16–0.44; P < 0.01) versus chemotherapy. PD-1 inhibitors prolonged OS mainly in the following patient groups: male, age <65 years, Eastern Cooperative Oncology Group performance status of 1, or PD-L1 tumor proportion score ≥10%. Asian patients had a longer OS than non-Asian patients (P = 0.01). ImplicationsThe available evidence indicates that the efficacy and tolerability of PD-1 inhibitors were better than chemotherapy in the second-line treatment of AEC, and the benefiting population of these patients was limited to males, those <65 years of age, those with a Eastern Cooperative Oncology Group performance status of 1, or those with a PD-L1 tumor proportion score ≥10%. Notably, Asian patients receiving immune monotherapy had longer OS than non-Asian patients.

Highlighting selected research conducted in older patients presented at the 23rd European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer (2021): Young International Society of Geriatric Oncology Report

The World Congress on Gastrointestinal Cancer 2021 organized by the European Society for Medical Oncology (ESMO) is the largest annual gathering for professionals caring for patients with gastrointestinal (GI) malignancies. Due to the COVID-19 pandemic, the congress was held virtually this year. Despite the online platform, 3200 attendees from 100 countries have participated, and about 50 oral presentations and 300 posters were presented. Here, we summarize the highlights presented in the field of geriatric oncology.

Interpretation of updated international guidelines for diagnosis and treatment of gastroenter-opancreatic neuroendocrine neoplasms

The incidence of neuroendocrine neoplasms (NEN) is continuously increasing with gastrointestinal tract and pancreas being the most common primary sites. Currently, the guidelines proposed by European Neuroendocrine Tumor Society (ENETS), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO) and North American Neuroendocrine Tumor Society (NANETS) are being widely applied. Among these, ENETS and NANETS guidelines were proposed in 2017 while ESMO and NCCN recently updated their guidelines for gastroenteropancreatic NEN in 2020 and 2021, respectively. This article interprets the diagnosis and treatment of gastroenteropancreatic NEN based on the newly updated ESMO and NCCN guidelines. The diagnosis of gastroenteropancreatic NEN depends on histological assessment including morphological evaluation, grading and immunohistochemistry results. Combination of different imaging methods can help determine tumor staging and risk assessment. Decision-making of treatment and follow-up strategies is based on primary tumor site, tumor classification, tumor grade, tumor type, functional status etc.

Female leadership in oncology—has progress stalled? Data from the ESMO W4O authorship and monitoring studies

BackgroundExploratory research showed that female oncologists are frequently under-represented in leadership roles. European Society for Medical Oncology (ESMO) Women for Oncology (W4O) therefore implemented gender equality programs in career development and established international studies on female representation at all stages of the oncology career pathway.MethodsFor 2017-2019, data were collected on (i) first and last authorship of publications in five major oncology journals and (ii) representation of women in leadership positions in oncology—as invited speakers at National/International congresses, board members or presidents of National/International societies and ESMO members. The 2015/2016 data from the first published W4O Study were incorporated for comparisons.ResultsAcross 2017-2019, female oncologists were significantly more likely to be first than last authors (P < 0.001). The proportion of female first authors was similar across years: 38.0% in 2017, 37.1% in 2018, 41.0% in 2019 (P = 0.063). The proportion of female last authors decreased from 30.4% in 2017 to 24.2% in 2018 (P = 0.0018) and increased to 28.5% in 2019 (P = 0.018). Across 2015-2019, invited speakers at International/National oncology congresses were significantly less likely to be female than male (P < 0.001; 29.7% in 2015 to 36.8% in 2019). Across 2016-2019, board members of International/National oncology societies were significantly less likely to be female than male (P < 0.001; 26.8% in 2016 to 35.8% in 2019). There were statistically significant increasing trends in female speakers and board members across the study periods (P < 0.001 for both). Societies with a female president had a higher proportion of female board members across these periods (P = 0.026).ConclusionsReported progress towards gender equality in career development in oncology is real but slow. Women in leadership positions are essential for encouraging young women to aspire to and work towards similar or greater success. Therefore, continued monitoring is needed to inform ESMO W4O initiatives to promote gender balance at all stages of the career pathway.

850 Addressing Fertility Preservation in Patients Under the Age of 35 Diagnosed with Breast Cancer. A Ten-Year Audit in A Regional Unit

Abstract Aim In Northern Ireland, the incidence of breast cancer is 1,443 cases per year with 26 patients diagnosed under the age of 35; 13% increase in 5 years. The average age of first-time mothers has increased from 24 to 28.8 in 2 decades. According to European Society of Medical Oncology, young patients should be counselled on available fertility preserving options before starting cancer treatment. Method We have conducted a retrospective audit reviewing the management of breast cancer patients under the age of 35 in the Belfast Health and Social Care Trust, with a focus on fertility counselling and patient’s options. Data obtained from Cancer Patient Pathway System and Patients records. Results From July 2010 to July 2020 there were 92 patients diagnosed with breast cancer in the region. All patients are female, youngest 24 years old. 34 patients have been referred as ‘Red Flag’, 22 upgraded to ‘Red Flag’, rest as routine. 23 patients received neo-adjuvant chemotherapy as first line treatment, 68 underwent surgery in the first instance, one patient opted for private sector. Over 50% of patients had at least one child prior to referral. Less than 5% had considered pregnancy post or during treatment. Conclusions At present there are no established guidelines regarding the timing of conception after diagnosis and treatment. Several options do exist for fertility preservation, both standard and investigational. There is evidence of an increasing recognition of this as a priority for patients and need early education and referral to fertility services for this emerging demographic.

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Adherence to European ovarian cancer guidelines and impact on survival: a French multicenter study (FRANCOGYN)

ObjectiveThe primary objective of the study was to validate the European Society for Medical Oncology (ESMO)–European Society of Gynecologic Oncology (ESGO) ovarian cancer guideline as a method of assessing quality...

Real-world trends in EU4 and the UK in frontline (1L) maintenance (MT) for nonsquamous (NSQ) advanced non-small cell lung cancer (aNSCLC) without actionable mutations after introduction of immune checkpoint inhibitors.

296 Background: Immune checkpoint (PD-1, PD-L1) inhibitors are important in the treatment (Tx) of aNSCLC, as reflected in European Society for Medical Oncology (ESMO) guidelines. Pembrolizumab (pembro) combined with pemetrexed and platinum-based chemotherapy is a standard induction option in 1L Tx of NSQ aNSCLC. Decisions about 1L maintenance consider response and toxicity after induction, performance status, and patient preference. This study documents recent real-world 1L MT patient characteristics and Tx in EU4 (France, Germany, Italy, Spain) and UK. Methods: This retrospective analysis used patient chart review completed by treating physicians in EU4 and UK between 1 Jan 2018 and 31 Dec 2020 in the IQVIA Oncology Dynamics (OD) database. Adults (≥21 years) with confirmed NSQ aNSCLC (stage IIIB/C or IV) without actionable oncogenic driver mutations and with Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 were included. 1L MT and Tx characteristics and trends over time were evaluated overall and by country. Results: In total, 1,814 NSQ aNSCLC patients receiving 1L MT Tx met the inclusion criteria; 29% of patients entered the analysis in 2018, 40% in 2019, and 31% in 2020. Most patients were male (61%), in the 46–65 age group (51%), current/ex-smokers (87%), and treated in the UK (29%) or Germany (24%); 94% were metastatic (stage IV), 10% presented with CNS/brain metastases, and 77% had ECOG score of 1. Overall, 91% were tested for PD-L1; of these, 47% had tumor proportion score (TPS) of ≥1% to 49%, 22% had TPS of ≥50%, and 21% tested negative. Baseline demographic and clinical characteristics were generally similar among countries. The top two Tx in 1L MT were pemetrexed (40%; range: 12% in Germany to 66% in Italy) and pembro (28%; range: 14% in Spain to 49% in Germany) monotherapies. Overall use of pemetrexed-based Tx in 1L MT decreased from 68% in 2018 Q1 to 56% in 2020 Q4, while pembro-based Tx increased from 18% in 2018 Q1 to 73% in 2020 Q4 in 1L MT. Conclusions: Despite ESMO guidelines, this real-world data suggests notable differences between European countries in 1L MT Tx for NSQ aNSCLC, with trends over time likely reflecting introduction and adoption of pembro regardless of PD-L1 status. Awareness of country and time-variability in clinical practice are critical for implementing clinical trials and updating clinical practice guidelines to maximize Tx benefits with improved tolerability.[Table: see text]

Treatment options for advanced urothelial cancer after progression on chemotherapy and immune checkpoint inhibitors: a literature review.

ObjectiveTo describe the current treatment landscape in advanced urothelial cancer (aUC)/metastatic urothelial cancer and in particular to review the relevant literature highlighting recent advances in the treatment of patients with aUC after progression on chemotherapy and immune checkpoint inhibitor (ICI).BackgroundaUC is a very aggressive disease with poor outcomes. Over the past several years, its treatment landscape has seen significant advances with the approval of ICI and targeted agents, which have led to improved outcomes. The current standard of care for most patients with aUC involves platinum-based chemotherapy followed by ICI after progression or as switch maintenance therapy (if no progression after chemotherapy). Treatment of patients following progression on ICI is more challenging, but novel therapies have been approved, such as erdafitinib for tumors with fibroblast growth factor receptor 2 (FGFR2) or FGFR3 activating mutation or fusion (can also be used following progression on platinum-based chemotherapy), enfortumab vedotin (EV) and sacituzumab govitecan (SG) in an unselected patient population. Many other trials in this space are currently ongoing and other promising agents may also potentially become available in the future.MethodsNarrative overview of the recent literature relevant to the treatment of advanced/metastatic urothelial cancer following progression on chemotherapy and ICI was undertaken. Relevant literature was obtained from review of computerized databases including pubmed.gov and proceedings of major conferences including American Society of clinical Oncology (ASCO) Meetings, GU ASCO Symposia and European Society of Medical Oncology (ESMO) Meetings.ConclusionsIn this narrative review, we highlight the current dynamic treatment landscape in aUC, emphasizing the recent important developments and a few examples of ongoing clinical trials. In particular, we focus on therapy options available following progression on platinum-based chemotherapy and ICI, a treatment space where until recently there had been no FDA-approved treatment options. The recent pivotal trials of antibody drug conjugates (ADCs) that led to FDA approvals in this space are highlighted, as are other agents currently in development. We conclude by discussing future directions and ongoing challenges in this evolving disease space.

Fertility and breast cancer: A literature review of counseling, preservation options and outcomes.

Fertility preservation is an important issue in breast cancer patients undergoing oncological treatment. Fertility counseling is a crucial need given the physical and psychological stress experienced by patients. Cryopreservation of mature oocytes is currently the standard fertility-preserving procedure. Other options such as ovarian tissue preservation or gonadal protection during chemotherapy are still experimental, but have proven effectiveness. Prompt referral to a fertility unit is highly recommended in order to ensure quality of care. In this article, we focus on the different strategies to preserve fertility in breast cancer patients, assessing also the safety of pregnancy and breastfeeding after cancer. A systemic literature review was performed for research articles published in English in PubMed, or as abstracts from the European Society for Medical Oncology (ESMO), San Antonio Breast Cancer Symposium (SABCS) and American Society of Clinical Oncology (ASCO) annual meetings, using the search terms "breast cancer" and "fertility".

ESMO 2021 Report — Breast Cancer

At this year's European Society of Medical Oncology (ESMO) Congress — held virtually September 16 to 21 in Paris, France — investigators reported the

Comparison of guidelines on rectal cancer: exception proves the rule?

The standard of care for early or locally advanced rectal cancer is promoted by multiple clinical practice guidelines globally, but the considerable differences between the guidelines may cause confusion. We compared the latest updated clinical practice guidelines from five professional societies/authorities: National Comprehensive Cancer Network, American Society of Colorectal Surgeons, European Society of Medical Oncology, Chinese National Health Commission, and Chinese Society of Clinical Oncology. Key evidence is discussed for a better understanding of some seemingly contradictory recommendations.

CLRM-14. OPEN-LABEL, MULTINATIONAL, MULTICENTER, PHASE 3B/4 STUDY OF TRASTUZUMAB DERUXTECAN (T-DXD) IN PATIENTS WITH OR WITHOUT BASELINE BRAIN METASTASIS (BM) WITH PREVIOUSLY TREATED ADVANCED/METASTATIC HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE BREAST CANCER (HER2+ BC): DESTINY-BREAST12

Abstract BACKGROUND Despite treatment advances, up to 50% of patients with advanced HER2+ BC develop BM (Zimmer. Cancer Rep. 2020). Patients with HER2+ BC with BM have a worse prognosis than patients without BM. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, median progression-free survival (PFS) of 19.4 and 18.1 mo, and median duration of response (DOR) of 20.8 and 16.9 mo (Modi. Cancer Res. 2021; Jerusalem. Ann Oncol. 2020). Here we describe a trial evaluating T-DXd in patients with previously treated advanced/metastatic HER2+ BC ±BM. DESIGN DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing T-DXd 5.4 mg/kg q3w efficacy and safety in patients with previously treated advanced/metastatic HER2+ BC ±BM that progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excluding patients with prior tucatinib). Patients (n=250/cohort) will be enrolled in cohort 1 (−BM at baseline) or 2 (+BM at baseline). BM must be untreated and not needing immediate local therapy or previously treated and stable or progressing. Primary endpoints are ORR (cohort 1) and PFS (cohort 2) (both by RECIST version 1.1 per ICR). Secondary endpoints are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL in both cohorts; incidence of new symptomatic CNS metastasis (CNSM) in cohort 1; and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM in cohort 2. This is an encore; the original presentation will be at The European Society for Medical Oncology 2021.

Local ablative treatment with surgery and/or radiotherapy in single-site and oligometastatic carcinoma of unknown primary

BackgroundSingle-site carcinoma of unknown primary (CUP) is recognised as a distinct favourable subtype in the European Society of Medical Oncology (ESMO) classification. There is broad consensus that these patients are candidates for local ablative treatment strategies with surgery and/or radiotherapy, but data on their outcomes are scarce. Patients and methodsIn this study, we have addressed the prospects of cure and prognostic factors in a retrospective cohort of 63 patients who were eligible for local treatment at our centre. ResultsMedian event-free (EFS) and overall survival (OS) were 15.6 months and 52.5 months, respectively. Of 61 patients who received local treatment, 20 (32.8%) remained event-free over a median follow-up of 28 months. Baseline clinical parameters including affected organ, number, volume and histology of metastases had no significant impact on prognosis, whereas deleterious TP53 mutations and DNA copy number loss emerged as independent adverse risk factors with respect to EFS. Surgical treatment was associated with improved OS as compared to radiation-based therapy. ConclusionOur study advocates to pursue localised treatment with surgery and/or radiotherapy whenever feasible and implies that genetic parameters might additionally determine the clinical course of single-site CUP patients.