Wong EYT, Verlingue L, Aldea M
… +18 more, Franzoi MA, Umeton R, Halabi S, Harbeck N, Indini A, Prelaj A, Romano E, Smyth E, Tan IB, Valachis A, Vibert J, Wiest IC, Yang YH, Gilbert S, Kapetanakis G, Pentheroudakis G, Koopman M, Kather JN
BACKGROUND: Large language models (LLMs) are rapidly being integrated into health care, with substantial implications for oncology practice. The European Society for Medical Oncology (ESMO) developed the ESMO guidance on...BACKGROUND: Large language models (LLMs) are rapidly being integrated into health care, with substantial implications for oncology practice. The European Society for Medical Oncology (ESMO) developed the ESMO guidance on the use of Large Language Models in Clinical Practice (ELCAP) to provide a structured framework and basic guidance for their safe and effective application in oncology. PATIENTS AND METHODS: Between November 2024 and February 2025, a multidisciplinary group of 20 experts convened under the ESMO Real World Data and Digital Health Task Force. Using literature review and a Delphi consensus process, the panel defined three categories of LLM use in oncology: type 1 (patient-facing applications), type 2 [health care professional (HCP)-facing applications], and type 3 (background institutional systems). Consensus statements were developed for each type to provide basic practical guidance. RESULTS: ELCAP highlights opportunities such as improved patient education and symptom management, streamlined clinical workflows, and enhanced data processing. At the same time, it addresses challenges including data privacy, algorithmic bias, regulatory compliance, and the risk of unsupervised use. The framework emphasises human oversight, protection of patient privacy, and alignment with clinical and ethical standards. Patient-facing tools should complement, not replace, professional advice and should be embedded in supervised care pathways. HCP-facing and background systems may improve efficiency and decision support but require systematic validation, transparency, and continuous monitoring. CONCLUSIONS: ELCAP provides a three-tier framework and basic practical guidance for LLM use in oncology. ESMO supports efforts to use this framework to improve patient care, but warns against unsupervised or unvalidated use.
Xu J, Chen J, Song S
… +31 more, Song L, Wang R, Hao J, Du X, Cao D, Gao Y, Lan X, Yang A, Miao W, Xu H, Chen Y, Li L, Shi H, Yuan X, Ye F, Wang J, Xu N, Han X, Li X, Huang R, Zhang T, Li E, Wang R, Zhou Y, Chen H, Zhu X, Zhao J, Su X, Cui Y, Ren P, Wang P
BACKGROUND: The phase III trial, XT-XTR008-3-01, was a randomised controlled trial (RCT) that evaluated the efficacy and safety of XTR008, a novel no-carrier-added lutetium-177 (Lu)-Dotatate, for the first time in a late...BACKGROUND: The phase III trial, XT-XTR008-3-01, was a randomised controlled trial (RCT) that evaluated the efficacy and safety of XTR008, a novel no-carrier-added lutetium-177 (Lu)-Dotatate, for the first time in a later-line therapy setting for gastroenteropancreatic neuroendocrine tumours (GEP-NETs) of all origins. PATIENTS AND METHODS: Patients with grade 1-2, unresectable, locally advanced or metastatic GEP-NETs who had progressed within the last 12 months before randomisation were randomly allocated 1 : 1 to XTR008 (four cycles every 8 weeks) or octreotide 60 mg (every 4 weeks), stratified by primary tumour site (pancreatic versus non-pancreatic), pathological tumour grade (1 versus 2), and duration of prior somatostatin analogues treatment (≤6 versus >6 months). The primary endpoint was progression-free survival (PFS) by a blinded independent review committee. The key secondary endpoints included overall response rate (ORR); overall survival (OS); quality of life, evaluated using the European Organisation for Research and Treatment of Cancer quality of life questionnaires QLQ-C30 and QLQ-GI.NET21; safety; pharmacokinetics; and dosimetry. RESULTS: Patients (N = 196) were randomized to XTR008 (n = 99) or control (n = 97). Primary tumour sites: pancreas (59%), rectum (28%), midgut (7%). Median follow-up: 11.1 months [interquartile range (IQR) 8.5-11.5, XTR008] versus 10.2 months (IQR 8.5-11.9 months, control). With 78 PFS events, median PFS was not reached [95% confidence interval (CI) 16.13 months to not estimated] versus 5.8 months (95% CI 5.65-8.41 months); stratified hazard ratio (HR) 0.06 (P < 0.0001). ORR: 43.4% (95% CI 33.50% to 53.77%) versus 1.0% (95% CI 0.03% to 5.61%). OS data were immature for both groups, with XTR008 showing a longer survival trend (HR 0.24, P = 0.0550). Treatment-related adverse events: 98% versus 89%; serious adverse events: 16.3% versus 12.5% (6.1% versus 3.1% drug-related). Myelodysplastic syndrome and grade ≥3 renal toxicity occurred in 1% of patients in the XTR008 group; no acute myeloid leukaemia or drug-related deaths occurred. CONCLUSIONS: XTR008 monotherapy showed superior efficacy versus high-dose long-acting repeatable (LAR) octreotide monotherapy in advanced GEP-NET tumours of all origins in a later-line treatment setting, with manageable safety, supporting its use as a new treatment option.
BACKGROUND: In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk ea...BACKGROUND: In the phase III PALLAS trial, the addition of 2 years of palbociclib to adjuvant endocrine therapy (ET) did not improve short-term invasive disease-free survival (iDFS) compared with ET alone in high-risk early-stage hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In this article, we report 5-year efficacy outcomes, including updated iDFS and overall survival (OS). PATIENTS AND METHODS: PALLAS is an international, open-label, randomized phase III trial evaluating the addition of 2 years of palbociclib to adjuvant ET in patients with stage II-III HR-positive/HER2-negative breast cancer. The primary endpoint was iDFS. RESULTS: The trial enrolled 5753 patients, with 2883 randomized to receive palbociclib plus ET and 2870 to receive ET alone. With a median follow-up of 59.8 months, the 5-year iDFS was 84.2% [95% confidence interval (CI) 82.7% to 85.6%] in the palbociclib plus ET arm and 82.4% (95% CI 80.8% to 83.9%) in the ET-alone arm [hazard ratio (HR) 0.88, 95% CI 0.77-1.01, log-rank P = 0.0614]. No significant iDFS benefit of palbociclib was observed in any subgroup, including analyses by anatomic stage, T-stage, N-stage, tumor grade, prior (neo)adjuvant chemotherapy, age, or clinical risk. The 5-year OS was 92.6% (95% CI 91.5% to 93.6%) in the palbociclib plus ET arm and 93.2% (95% CI 92.1% to 94.1%) in the ET-alone arm (HR 1.09, 95% CI 0.89-1.33, log-rank P = 0.4051). More patients in the ET-alone arm (65.7%) than in the palbociclib plus ET arm (33.0%) received cyclin-dependent kinase 4/6 inhibitors after recurrence. Conversely, more patients in the palbociclib plus ET arm (52.5%) than in the ET-alone arm (41.0%) received chemotherapy after recurrence. CONCLUSIONS: In conclusion, 5-year follow-up from the PALLAS trial confirms initially reported results. These long-term findings will provide investigators with important benchmarks for clinical outcomes in the contemporary management of HR-positive/HER2-negative breast cancer, and may be further used to guide adjuvant therapy for patients with high-risk early-stage HR-positive/HER2-negative breast cancer.
Powles T, Hussain SA, Climent MA
… +18 more, Carbonero IG, Molina-Cerrillo J, Puente J, Borrega P, Malik J, Dourthe LM, Jones R, Castellano D, Durán I, Loriot Y, Priyadarshini G, Szabados B, Jamal F, Wang YQ, Kotriwala N, Jackson-Spence F, Ackerman C, Grande E
BACKGROUND: Six cycles of platinum-based chemotherapy followed by avelumab continues to be used in some circumstances in advanced/metastatic urothelial cancer (mUC). To investigate whether shorter chemotherapy duration i...BACKGROUND: Six cycles of platinum-based chemotherapy followed by avelumab continues to be used in some circumstances in advanced/metastatic urothelial cancer (mUC). To investigate whether shorter chemotherapy duration improves quality of life (QoL) without worsening efficacy, this study compared three versus six cycles followed by avelumab. PATIENTS AND METHODS: This randomized phase II trial compared three versus six cycles (3C arm versus 6C arm) of chemotherapy followed by avelumab in patients receiving first-line treatment for mUC. This trial had co-primary endpoints of patient-reported outcomes (PROs), defined as change from baseline to cycle 6 on the global health status/QoL score, and superior overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate, and safety. Here, we report the final PRO analysis and interim OS. RESULTS: A total of 267 patients were randomized (133 to 3C arm, 134 to 6C arm). Forty-two percent received gemcitabine/cisplatin and 58% gemcitabine/carboplatin. Seventy-eight percent and 40% of patients completed three and six cycles as allocated. Seventy-four percent of patients received avelumab in the 3C arm, versus 56% in the 6C arm. The mean QoL change between baseline and cycle 6 was 0 [95% confidence interval (CI) -5.9 to 5.2] in the 3C arm versus -8.5 (95% CI -14.1 to -2.9) in the 6C arm, with a significant difference favouring 3C (+8.5 points, 95% CI 0.7-16.3, P = 0.016). Improvement in PRO scores was observed in 41% (3C arm) versus 24% (6C arm) of patients. OS was not significant (18.9 months in both arms [hazard ratio (HR) 1.15, 95% CI 0.72-1.86, P = 0.56]. Median PFS was 8.0 months (95% CI 6.7-11.9 months) in the 3C arm versus 9.0 months (95% CI 6.9-12.7 months) in the 6C arm (HR 1.05, 95% CI 0.73-1.53). Median grade 3-4 treatment-related adverse events occurred in 11.9% (3C arm) versus 15.7% (6C arm). CONCLUSIONS: Three cycles of chemotherapy followed by maintenance avelumab is associated with better QoL than six cycles. Randomized trials with patient-focused outcomes exploring shorter duration of therapy are feasible (NCT06892860).
Johnston S, Martin M, O'Shaughnessy J
… +24 more, Hegg R, Tolaney SM, Guarneri V, Del Mastro L, Campone M, Sohn J, Boyle F, Cortes J, Rugo HS, Goetz MP, Hamilton EP, Huang CS, Senkus E, Cicin I, Testa L, Neven P, Huober J, Shao Z, Wei R, Munoz M, San Antonio B, Shahir A, Rastogi P, Harbeck N
BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-n...BACKGROUND: Adjuvant abemaciclib combined with endocrine therapy (ET) significantly improved invasive disease-free survival (IDFS) in patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, node-positive, high-risk early breast cancer (EBC). The impact on overall survival (OS) remained unknown. PATIENTS AND METHODS: In the phase III monarchE trial (NCT03155997), patients received ET for at least 5 years with or without abemaciclib for 2 years. In this article, we report the primary OS results, a key secondary endpoint, and updated estimates of IDFS and distant relapse-free survival (DRFS). RESULTS: Overall, 5637 patients underwent randomization, with 2808 assigned to abemaciclib-ET, and 2829 to ET. In the intent-to-treat population, with a median follow-up of 76.2 months, abemaciclib-ET resulted in a 15.8% lower risk of death than ET [661 deaths; hazard ratio 0.842, 95% confidence interval (CI) 0.722-0.981, P = 0.027], meeting the prespecified boundary for significance. The 7-year OS was 86.8% with abemaciclib-ET and 85.0% with ET (absolute difference, 1.8%). OS benefit was consistent across prespecified subgroups. In addition to patients who had already died of metastatic disease, fewer patients in the abemaciclib-ET arm were living with metastatic disease compared with the ET arm (6.4% versus 9.4%). Sustained improvement was demonstrated in IDFS and DRFS (hazard ratio 0.734, 95% CI 0.657-0.820 and hazard ratio 0.746, 95% CI 0.662-0.840, respectively). Seven-year IDFS was 77.4% with abemaciclib-ET and 70.9% with ET (absolute difference, 6.5%) and 7-year DRFS were 80.0% and 74.9% (absolute difference, 5.1%). The long-term safety data compiled did not support any concerns of delayed toxicities. CONCLUSIONS: Adjuvant abemaciclib-ET resulted in a statistically significant and clinically meaningful improvement in OS compared with ET in patients with HR-positive, HER2-negative, node-positive, high-risk EBC. At 7 years, abemaciclib-ET continued to demonstrate a sustained IDFS and DRFS benefit.
Molassiotis A, Jordan K, Karthaus M
… +20 more, Dranitsaris G, Roeland EJ, Schwartzberg L, Stimamiglio V, Alonzi A, Olivari Tilola S, Bonizzoni E, Brozos Vázquez E, Buchler T, Cheng Y, Christoph DC, García Alfonso P, Lu X, Majem M, Mavroudis D, Syrigos K, Tomlins E, Zhou Z, Zimovjanová M, Aapro M
BACKGROUND: Patients receiving moderately emetogenic chemotherapy (MEC) are commonly prescribed a 5-hydroxytryptamine-3 (5-HT) receptor antagonist (RA) and dexamethasone (DEX) as standard-of-care (SOC) antiemetic prophyl...BACKGROUND: Patients receiving moderately emetogenic chemotherapy (MEC) are commonly prescribed a 5-hydroxytryptamine-3 (5-HT) receptor antagonist (RA) and dexamethasone (DEX) as standard-of-care (SOC) antiemetic prophylaxis. However, in patients with an elevated risk of chemotherapy-induced nausea and vomiting (CINV) due to individual risk factors, prophylaxis with an neurokinin-1 (NK) RA-containing regimen may optimise their antiemetic prevention. To address this unmet need for a more personalised antiemetic strategy, the MyRisk trial incorporated a predictive risk factor algorithm to select patients at increased risk of CINV who may benefit from enhanced antiemetic prophylaxis. PATIENTS AND METHODS: MyRisk was a phase IV, randomised, open-label, multicentre, multinational trial. Adult patients scheduled to receive three cycles of MEC with a high-risk CINV score were randomly assigned to NEPA (a fixed combination of an NK RA, netupitant, and 5-HT RA, palonosetron) + DEX or SOC. The CINV risk score was calculated based on an algorithm that considered seven risk factors. The primary endpoint was complete response (CR: no emesis/no rescue medication) during the overall phase (0-120 h) across three consecutive cycles. RESULTS: Of 401 randomly allocated patients, 388 were included in the efficacy analysis. The most common cancers were colorectal and lung; oxaliplatin and carboplatin were the most common MECs. Patients randomly assigned to NEPA were significantly more likely to experience a CR compared with SOC (odds ratio 1.67, 95% confidence interval 1.12-2.49, P = 0.012). The NEPA group had a significantly higher probability of CR, no nausea, no emesis, and complete protection (81.0%, 63.7%, 95.4%, and 71.8%, respectively) compared with the SOC arm (71.8%, 54.9%, 86.7%, and 62.4%, respectively) across three cycles of chemotherapy. CONCLUSIONS: When individual risk factors are considered before MEC, a three-drug regimen including NEPA provides superior CINV prevention across multiple cycles compared with the standard two-drug approach. These findings underscore the value of personalised risk-adapted antiemetic strategies and have practice-changing potential for optimising antiemetic control.
Mayer EL, Trapani D, Kim SE
… +17 more, Faggen M, Sinclair N, Sanz-Altamira P, Battelli C, Berwick S, Lo S, Acevedo J, Sinclair S, Malcolm A, Varella L, Sammons S, Schumer S, Poorvu PD, Wallace E, Pasternak E, Tayob N, Tolaney SM
BACKGROUND: Adjuvant abemaciclib with endocrine therapy (ET) improves clinical outcomes in patients with high-risk node-positive early-stage hormone receptor-positive/HER2-negative (HR-positive/HER2-negative) breast canc...BACKGROUND: Adjuvant abemaciclib with endocrine therapy (ET) improves clinical outcomes in patients with high-risk node-positive early-stage hormone receptor-positive/HER2-negative (HR-positive/HER2-negative) breast cancer (BC), based on the monarchE trial. Patients may experience tolerability issues at the standard abemaciclib dose [150 mg twice daily (b.i.d.)], potentially leading to early treatment discontinuation, particularly within the initial weeks of therapy. TRADE is a prospective, single-arm, phase II study evaluating whether dose escalation of adjuvant abemaciclib improves drug tolerability. PATIENTS AND METHODS: Eligible patients had node-positive HR-positive/HER2-negative BC and were candidates for adjuvant abemaciclib with ET. Participants initiated abemaciclib at 50 mg b.i.d. for 2 weeks, then escalated to 100 mg b.i.d. for 2 weeks, then escalated to the final dose level (150 mg b.i.d.). Dose escalation required the absence of ongoing grade 3-4 or persistent grade 2 toxicity. The primary endpoint, measured at 12 weeks, was a composite rate of abemaciclib discontinuation for any reason or inability to reach or maintain the target dose. RESULTS: In 89 evaluable patients, the initial dose escalation strategy significantly reduced the composite rate at 12 weeks versus a historical value of 40% from monarchE. In total, 26/89 participants (29.2%, 90% confidence interval 21.3% to 38.2%, P = 0.023) met the endpoint: 6 (6.7%) for early discontinuation, 8 (9.0%) for inability to reach 150 mg, and 12 (13.5%) for dose reduction from 150 mg. The majority (70.8%) reached and maintained 150 mg b.i.d. dosing. CONCLUSION: Use of an adjuvant abemaciclib dose escalation strategy allowed more patients to reach and maintain target dosing at 12 weeks than observed in monarchE. Early discontinuation was infrequent, and 93.3% of patients were continuing therapy at 12 weeks. This dosing strategy could be considered when initiating adjuvant abemaciclib.
Galsky MD, Gschwend JE, Milowsky MI
… +18 more, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Agerbaek M, Jha G, Stenner F, Ye D, Giudici F, Connors J, Gupta S, Chhibber A, Zhang J, Bajorin DF, Witjes JA
BACKGROUND: Despite surgery, recurrence rates remain high in muscle-invasive urothelial carcinoma (MIUC). The phase III randomized, double-blind, multicenter CheckMate 274 trial comparing adjuvant nivolumab versus placeb...BACKGROUND: Despite surgery, recurrence rates remain high in muscle-invasive urothelial carcinoma (MIUC). The phase III randomized, double-blind, multicenter CheckMate 274 trial comparing adjuvant nivolumab versus placebo in patients with high-risk MIUC after radical surgery demonstrated that adjuvant nivolumab improved disease-free survival (DFS) versus placebo. We report results with 5-year minimum follow-up including exploratory analyses of circulating tumor DNA (ctDNA). PATIENTS AND METHODS: Eligible patients had radical surgery (R0, with negative surgical margins) within 120 days before being randomized, with or without neoadjuvant cisplatin-based chemotherapy. Overall, 709 patients with MIUC at high risk of recurrence after surgery were randomly assigned 1:1 to nivolumab 240 mg or placebo every 2 weeks for ≤1 year. The primary endpoint was DFS. Overall survival (OS) was a key secondary endpoint. In a post hoc exploratory analysis, baseline ctDNA was measured using the Signatera assay. RESULTS: Median DFS was 21.9 months [95% confidence interval (CI) 18.8-36.9 months] with nivolumab versus 11.0 months (95% CI 8.3-16.6 months) with placebo in all randomized patients [hazard ratio (HR) 0.74, 95% CI 0.61-0.90], and 55.5 months (95% CI 25.8-66.5 months) versus 8.4 months (95% CI 5.6-20.0 months) in patients with tumor programmed death-ligand 1 expression ≥1% (HR 0.58, 95% CI 0.42-0.79). In all randomized patients, median OS was 75.0 months (95% CI 56.7 months-not estimable) with nivolumab versus 50.1 months (95% CI 38.0-72.1 months) with placebo (HR 0.83, 95% CI 0.67-1.02). Baseline ctDNA after radical surgery was detected in 54 (40.6%) of 133 assessable patients. Median DFS was 52.1 months (95% CI 19.4 months-not estimable) versus 5.0 months (95% CI 2.8-6.5 months) in patients with undetectable versus detectable ctDNA at baseline (HR 0.30, 95% CI 0.18-0.48). In patients included in the ctDNA analysis who had detectable ctDNA, the median DFS HR for nivolumab-treated patients versus placebo-treated patients was 0.35 (95% CI 0.18-0.66), while in patients with undetectable ctDNA, the HR for nivolumab-treated patients versus placebo-treated patients was 0.99 (95% CI 0.51-1.93). There were no new safety signals. CONCLUSIONS: Five-year results confirm durable DFS benefit and consistent safety profile for adjuvant nivolumab in high-risk MIUC. Post hoc exploratory ctDNA assessment identified patients at highest risk of recurrence and may inform tailored adjuvant therapy strategies, pending further validation.
BACKGROUND: ALEX, a global, randomized, phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). This final analysis provides mature overall surviva...BACKGROUND: ALEX, a global, randomized, phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). This final analysis provides mature overall survival (OS), duration of response (DOR) and long-term safety data. PATIENTS AND METHODS: Treatment-naïve patients with stage III/IV ALK-positive NSCLC were randomly assigned to receive alectinib [600 mg twice daily (b.i.d.)] or crizotinib (250 mg b.i.d.) until disease progression, unacceptable toxicity, withdrawal, or death. Primary endpoint was investigator-assessed progression-free survival (previously reported). Key secondary endpoints included OS, DOR and safety. RESULTS: A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled. At the updated data cut-off (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence interval (CI) 62.3 months-not estimable] versus 54.2 (95% CI 34.6-75.6 months) months, respectively [hazard ratio (HR) 0.78; 95% CI 0.56-1.08]. Improvement in median OS was observed with alectinib in patients with and without central nervous system (CNS) metastases at baseline [with CNS metastases: 63.4 (n = 59) versus 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); without CNS metastases: 94.0 (n = 93) versus 69.8 (n = 98) months (HR 0.87; 95% CI 0.58-1.32)]. Median DOR in confirmed responders was longer with alectinib (42.3 months, 95% CI 31.3-51.3 months) versus crizotinib [11.1 months, 95% CI 7.9-13.0 months (HR 0.41; 95% CI 0.30-0.56)]. Long-term safety (median duration of alectinib treatment, 28.1 months) remained consistent with earlier reports, with no new or unexpected safety concerns identified. CONCLUSIONS: These final OS data show the sustained long-term systemic and intracranial efficacy of alectinib in the first-line treatment of ALK-positive NSCLC and confirm alectinib as a standard of care in this setting.
BACKGROUND: Standard treatment of high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor is intravesical instillation with Bacillus Calmette-Guérin (BCG) (induction and mainte...BACKGROUND: Standard treatment of high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor is intravesical instillation with Bacillus Calmette-Guérin (BCG) (induction and maintenance regimens); however, BCG therapy still fails in 30%-40% of patients. Prior studies suggest that programmed death-ligand 1 (PD-L1) expression and alterations in immune infiltration might be associated with BCG failure. PATIENTS AND METHODS: The ALBAN trial is an international, 1 : 1 randomized, open-label phase III trial comparing the combination of atezolizumab (an anti-PD-L1 antibody) and BCG (arm B) versus BCG alone (arm A) for BCG-naive patients with high-risk NMIBC. The primary endpoint was investigator-assessed event-free survival (EFS). Key secondary endpoints included high-grade recurrence-free survival, complete response rate, and duration of response in patients with carcinoma in situ disease, as well as overall survival. RESULTS: In total, 255 patients were randomly assigned to arm A and 262 to arm B. The trial did not meet its primary endpoint; there was no significant difference in EFS between arms, with a hazard ratio of 0.98 (95% confidence interval 0.71-1.36, P = 0.9106). EFS results were consistent across all prespecified subgroups. The safety profile of the treatment combination was consistent with that of the individual agents but showed higher rates of treatment-related adverse events (TRAEs) and grade ≥3 TRAEs than BCG alone. CONCLUSION: This phase III trial in BCG-naive patients with high-risk NMIBC did not demonstrate an EFS benefit from the addition of atezolizumab to 1-year BCG therapy, in contrast to positive EFS results reported with another PD-(L)1 agent, suggesting that any benefit from checkpoint-BCG therapy may be context- and agent-specific rather than a class effect. Future research should focus on biomarker-driven patient selection and optimization of the timing, duration, and route of checkpoint delivery relative to BCG.
Malorni L, Tyekucheva S, Gombos A
… +20 more, Hasler-Strub U, Zamagni C, Chakiba-Brugère C, Colleoni M, Mueller A, Minisini AM, Taylor D, Salmon JP, Gallerani E, Cariello A, Fontana A, Roschitzki-Voser H, Kammler R, Ruepp B, Loi S, Viale G, Regan MM, Brain E, Biganzoli L, International Breast Cancer Study Group (a division of ETOP IBCSG Partners Foundation) and the TOUCH Trial (IBCSG 55-17) Investigators
BACKGROUND: Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a heterogeneous disease with low pathological complete response (pCR) to standard neoadjuvant trea...BACKGROUND: Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a heterogeneous disease with low pathological complete response (pCR) to standard neoadjuvant treatment. Cyclin-dependent kinase 4 and 6 inhibitors with endocrine and anti-HER2 therapy have shown a potential for chemotherapy omission in this context. PATIENTS AND METHODS: TOUCH is an international, open-label, phase II trial for postmenopausal patients with cT >1 cm, cN0 or cN1, HR-positive/HER2-positive BC, randomly assigned to 16 weeks of neoadjuvant weekly paclitaxel or palbociclib and letrozole, both with trastuzumab + pertuzumab (HP). The primary objective investigated the interaction between a gene signature of E2F pathway activity (RBsig) and pCR (ypT0N0 or ypTisN0), hypothesizing higher pCR for RBsig-high tumors in the paclitaxel + HP group and for RBsig-low tumors in the palbociclib + letrozole + HP group. RBsig was assessed by RNA-sequencing from pre-treatment biopsies; intrinsic subtypes were estimated by absolute intrinsic molecular subtyping Treatment-by-biomarker interaction was estimated using logistic regression in 115 assessable patients. RESULTS: A total of 147 patients were randomly assigned (74 paclitaxel + HP, 73 palbociclib + letrozole + HP) and 145 constituted the treated population, with a median age of 69 years (interquartile range 63-73 years). More patients completed palbociclib versus paclitaxel (94.4% versus 79.5%). The most frequent grade 3-4 adverse events were neutropenia and diarrhea (6.9% versus 43.1% and 11% versus 8.3% in the paclitaxel + HP versus the palbociclib + letrozole + HP groups, respectively). The pCR rate was 32.9% [95% confidence interval (CI) 22.3% to 44.9%] in the paclitaxel + HP group and 33.3% (95% CI 22.7% to 45.4%) in the palbociclib + letrozole + HP group. No significant treatment-by-RBsig interaction was observed (P = 0.18): pCR in RBsig high versus low was 31.3% (95% CI 16.1% to 50.0%) versus 42.3% (95% CI 23.4% to 63.1%) in the paclitaxel + HP group, and 38.5% (95% CI 20.2% to 59.4%) versus 25.8% (95% CI 11.9% to 44.6%) in the palbociclib group. pCR was higher in non-luminal versus luminal subtypes (45.5% versus 18.4%), with no interaction with treatment. CONCLUSIONS: Although the primary hypothesis was not supported, TOUCH shows that dual anti-HER2 blockade with a chemotherapy-free backbone of palbociclib + letrozole yields pCR rates similar to paclitaxel, representing an attractive alternative treatment strategy.
Bompas E, Le Cesne A, Tresch-Bruneel E
… +13 more, Lebellec L, Laurence V, Collard O, Saada-Bouzid E, Isambert N, Blay JY, Amela EY, Salas S, Chevreau C, Bertucci F, Italiano A, Clisant S, Penel N
Goetz MP, Toi M, Huober J
… +19 more, Sohn J, Trédan O, Park IH, Campone M, Chen SC, Manso LM, Paluch-Shimon S, Freedman OC, O'Shaughnessy J, Pivot X, Tolaney SM, Hurvitz SA, Llombart-Cussac A, André V, Saha A, van Hal G, Shahir A, Iwata H, Johnston SRD
Burstein HJ, Curigliano G, Gnant M
… +10 more, Loibl S, Regan MM, Loi S, Denkert C, Poortmans P, Cameron D, Thurlimann B, Weber WP, Panelists of the St. Gallen International Breast Cancer Consensus 2025. Electronic address: https://twitter.com/SG_BCC, Panelists of the St. Gallen International Breast Cancer Consensus 2025
BACKGROUND: Breast cancer is a global disease affecting millions of individuals. Ongoing advancements in multidisciplinary management of breast cancer patients warrant discussion and integration into standard treatment p...BACKGROUND: Breast cancer is a global disease affecting millions of individuals. Ongoing advancements in multidisciplinary management of breast cancer patients warrant discussion and integration into standard treatment plans. DESIGN: The St Gallen Breast Cancer Consensus conference is an international, biennial meeting where experts make treatment recommendations for state-of-the-art care of early stage breast cancer. RESULTS: Important innovations in the 2025 St Gallen recommendations include updated guidance on genetic testing; endorsement of hypofractionated, and ultra-hypofractionated, radiation therapy schedules for larger numbers of patients; recommendation for platinum-based chemotherapy in triple-negative breast cancer, and use of biological risk markers to consider anthracyclines in other breast cancer subtypes; avoidance of sentinel lymph node surgery in many patients with low-risk, estrogen receptor (ER)-positive cancers; use of immunotherapy in triple-negative and certain ER low-positive tumors; guidance for re-irradiation and systemic therapy in the setting of local-regional recurrence; criteria to guide treatment of oligometastatic breast cancer; and important recommendations for improving survivorship by minimizing neuropathy symptoms and addressing sexual health concerns of breast cancer patients. CONCLUSIONS: International, multidisciplinary guidance for early breast cancer is evolving and offers patients better outcomes, improved treatment choices, and greater concern for patient preferences and survivorship needs.