Triple Negative Breast Cancer (TNBC) poses significant challenges due to its aggressiveness, high relapse rate and mortality. Neoadjuvant immuno-chemotherapy (NAIC) is now a common treatment for early-stage TNBC before surgery. NAIC aims to eliminate viable cancer in the tumor, lymph nodes and possible occult distant metastases, shrink tumors to improve surgical outcomes and prevent disease recurrence. The Keynote-522 study revealed a 84.5% 3-year event-free survival in patients with early-stage TNBC using NAIC and improved pathological complete response (pCR) rates from 51.2% with neoadjuvant Chemotherapy to 64.8% with NAIC. A new potential method to improve clinical outcome and induce immune activation pre-surgery is through a novel local therapy in combination with NAIC that could cause increased apoptotic cell death and create personalized tumor antigens. Arnaout et al. conducted a randomized, phase 2 neoadjuvant window of opportunity trial using intratumoral (IT) INT230-6, a drug comprising vinblastine, cisplatin and a tumor dispersion and cell penetration enhancer molecule (SHAO), evaluating clinical and biological effects in women with early-stage operable BC (NCT04781725). Results in T2 to T4 tumors showed an average of over 30% necrosis in 74% of subjects at the time of surgery, with some patients having >95% tumor necrosis following a single dose. Adding immune-activating and apoptotic induced necrosis caused by INT230-6 dosed prior to NAIC in TNBC patients has the potential to increase pCR. This is a randomized, open-label multicenter phase 2 clinical study to determine the clinical activity, safety, and tolerability of IT INT230-6 in patients with early-stage, operable TNBC in combination with NAIC (cohort A) or NAIC alone (cohort B). The INT230-6 dose is dependent on tumor size. The primary endpoint is pCR in the primary tumor (ypT0/Tis) and affected lymph nodes (ypN0). Key inclusion criteria include newly diagnosed, previously untreated, locally advanced non-metastatic TNBC stage cT1c N1-3 M0 or cT2-4c N0-3 M0. Multifocal and multicentric primary tumors are allowed. Patients must have measurable disease in the breast with at least one lesion with a diameter ≥1.5 cm visible in ultrasound and injectable. Patients are either male or female, age ≥ 18 years, ECOG performance status <2, adequate bone marrow, hepatic and renal function. STATS: The sample size calculation for both cohorts is determined based on a single-stage phase II single-arm clinical trial design (A’Hern). Null hypothesis (H0): pCR rate ≤ 0.6, Alternative hypothesis (H1): pCR rate ≥ 0.8. Type I error: 10% (one-sided), Power: 80%. The duration for accrual, patient therapy and follow-up is 12, 8 and 36 months respectively. The sample size per cohort is 27 patients. The study is recruiting in Switzerland and France in up to 16 sites. By July 2025 15 of 54 patients could be enrolled, completion of accrual is expected in 2026. Preliminary safety data do not show unexpected or severe INT230-6 related adverse events. pCR results become available 6 months after the last patient starts the SOC and undergoes surgery. An exemplary case of a patient will be shown. U. Zürrer, A. Müller, O. Tredan, C. Micheloud, J. Musilova, R. Popescu, T. Schmid, L. Rossi, M. Schwitter, M. Vetter, M. Niemeyer, I. Witzel, A. Patsouris, S. Ladoire, J. Martin-Babau, A. Deleuze, M. Robert, L. H. Bender, M. Joerger. Intratumoral Injections of INT230-6 Prior to Neoadjuvant Immuno-chemotherapy in Early-Stage Triple Negative Breast Cancer: Early observations from INVINCIBLE-4-SAKK 66/22 (NCT06358573), a Phase II Randomized Controlled Trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-08-16.
Cancer survivors face an increased risk of second primaries, but adherence to cancer screening and prevention recommendations remains limited. Post-treatment follow-up visits represent teachable moments for health promotion, including prevention of second primary cancers. We assessed practices and perceptions of second cancer screening and prevention among French hospital-based oncology health care professionals. An anonymous online survey using Likert scale was conducted. Clustering identified three prevention activity profiles (low, intermediate, high), and multinomial logistic regression explored associated factors. The median declared promotion activity of the 415 respondents was 8 for mammographic screening ([interquartile range: 5-10), 7 (2-9) for cervical cancer screening, 5 (1-7) for colorectal screening, 9 (7-10) for smoking cessation, and 7 (5-9) for alcohol control. Seventy-five percent of respondents addressed obesity management if indicated. Perceived importance and feasibility of secondary prevention activities were high [9 (7-10) and 8 (6-10)]. A high prevention activity profile was associated with greater perceived importance of secondary prevention [odds ratio (OR) per one-point Likert-scale increase = 1.1, 95% confidence interval (CI): 1.04-1.2] and its feasibility (OR = 1.1, 95% CI: 1.06-1.14); and managing head and neck cancer patients (OR = 7.64, 95% CI 1.55-37.8). Lung and sarcoma specialists were less likely to be in the high prevention activity group. Hospital-based oncology health care professionals are aware of and engaged in second primary cancer prevention, though activity levels vary. Its generalization, organization, and development could improve cancer survivors' adherence to cancer prevention recommendations, and improve health impacts.
PURPOSE:Mismatch repair deficiency (dMMR) or microsatellite instability (MSI) represents a distinct phenotype among solid tumors resulting in the generation of highly immunogenic neoantigens. Pembrolizumab has been approved in first-line unresectable or metastatic dMMR/MSI colorectal cancers (CRC). We aimed to assess efficacy and tolerance of perioperative pembrolizumab in dMMR/MSI CRC. PATIENTS AND METHODS:The prospective multicenter phase II trial IMHOTEP enrolled patients with localized resectable dMMR/MSI CRC to receive one or two cycles of IV pembrolizumab 400 mg once every 6 weeks before surgery and 1-year total duration thereafter. The primary end point was pathologic complete response (pCR) rate (ypT0N0). Secondary objectives included safety, event-free survival, and overall survival. RESULTS:IMHOTEP enrolled 81 patients with dMMR/MSI CRC who received at least one cycle of pembrolizumab from November 26, 2021, to February 22, 2023: median age was 66 (21-89) years, 46 (52%) were women, and 63 (71%) had clinical stage III disease at baseline. Out of the 72 patients included in the efficacy population, 38 patients (52.7% [95% CI, 41.4 to 63.9]) achieved a pCR. The exploratory post hoc analysis showed a pCR rate increased from 46% (23/50) after one cycle to 68.2% (15/22) after two cycles of neoadjuvant pembrolizumab (P = .0125). With a median follow-up of 24.5 (95% CI, 23.3 to 25.6) months, three disease recurrences occurred. Grade ≥3 immune-related toxicities were reported in 14 (15.7%) patients including one grade 5 (myasthenia). CONCLUSION:The IMHOTEP trial showed promising results, with pCR achieved after one or two cycles of neoadjuvant pembrolizumab in 53% of patients with dMMR/MSI CRC. To our knowledge, this prospective study is the first to demonstrate the feasibility and the safety of perioperative pembrolizumab.
The treatment of advanced primary liver cancer has seen major improvement in recent years. In hepatocellular carcinoma (HCC), immunotherapy has improved both survival and quality of life. In biliary tract cancers (BTC), immunotherapy has shown modest benefits, while molecular targeted therapies have had a major impact in selected populations defined by molecular alterations. These advances are now being tested at earlier disease stages. In this review, we first discuss the challenges in designing trials that combine local and systemic treatment at earlier stages, and the different endpoints that might be used. We then present the available data on the combination of intra-arterial and systemic treatments in HCC. We continue with a discussion of the available data on adjuvant and neoadjuvant systemic treatment in HCC. Finally, we review recent developments in the adjuvant and neoadjuvant settings for BTC. While promising data exist across these settings, uncertainties remain regarding whether these strategies will become standard of care in the coming years.
The management of unresectable and advanced hepatocellular carcinoma (HCC) has been transformed by the introduction of immune checkpoint inhibitor-based combinations, which have improved response and survival and expanded first-line treatment options. The availability of multiple effective regimens has introduced new challenges in therapeutic decision making. In the absence of validated predictive biomarkers or head-to-head comparisons, first-line treatment selection remains largely guided by clinical characteristics, contraindications and anticipated toxicity, while the optimal sequencing of therapy following first-line immunotherapy remains uncertain. Locoregional therapies continue to play an important role in selected patients with liver-confined disease, further broadening the range of therapeutic strategies available in clinical practice. In Europe, these evolving treatment paradigms are implemented within a heterogeneous landscape of regulatory approval, reimbursement and access, resulting in important differences in care across countries. In this Series paper, we discuss contemporary systemic treatment strategies for HCC from a European perspective, focusing on treatment selection and sequencing, the role of predictive biomarkers and locoregional therapies, and disparities in access to effective treatments. Generating prospective evidence to inform treatment selection and sequencing, while ensuring more timely and equitable access to effective therapies will be essential to optimise HCC care across Europe.
