ESMO 20264Sight

CLARITY-Gastric 01 (CG-01): A Phase 3 Study of Sonesitatug Vedotin (Sone-Ve) in Second or Later-Line (2L+) Advanced or Metastatic Claudin 18.2 (CLDN18.2)-Positive Gastroesophageal Carcinoma (GEC)

Phase 3 (n=532): sonesitatug vedotin (CLDN18.2-targeted ADC) vs investigator’s choice in 2L+ CLDN18.2-positive (≥25%) advanced GEC. Dual primary endpoints: OS in 3L+ and PFS in ITT.

• 3L+ OS: 10.0 vs 5.0 mo; HR 0.47 (0.36–0.62)
• ITT OS: 10.6 vs 6.4 mo; HR 0.58 (0.47–0.73); PFS HR 0.77, not significant
• Grade ≥3 TRAEs 36.4% vs 44.8%
• Significant OS benefit in 3L+ and ITT with a manageable safety profile, supporting Sone-Ve as a potential 2L+ treatment.

Rui-Hua Xu

Yelena Janjigian · Ming-Huang Chen

Osimertinib + Savolitinib vs Platinum–Pemetrexed in EGFRm MET-Overexpressed and/or -Amplified Advanced NSCLC Post-Osimertinib: SAFFRON Phase 3 Primary Results

Phase 3 (n=338): osimertinib + savolitinib vs platinum–pemetrexed in EGFRm, MET-overexpressed and/or amplified advanced NSCLC after osimertinib. Primary endpoint: PFS by BICR.

• Median PFS 7.6 vs 5.4 mo; HR 0.55 (0.42–0.72); p<0.001
• Median OS 17.8 vs 12.9 mo; HR 0.68 (0.50–0.91); p=0.010
• Grade ≥3 TRAEs 40% vs 52%; serious TEAEs 41% vs 28%
• Significant PFS and OS improvement with a manageable safety profile, establishing a new global standard of care.

Shun Lu

Nicolas Girard · Yusuke Okuma

Krascendo 1: Efficacy and Safety of Divarasib vs Sotorasib or Adagrasib in Previously Treated Locally Advanced or Metastatic KRAS G12C-Mutated NSCLC

Phase 3 (n=338): divarasib vs investigator’s choice of sotorasib or adagrasib in previously treated advanced KRAS G12C-mutated NSCLC. Primary endpoint: PFS by BICR; median follow-up 14.3 mo.

• Median PFS 9.8 vs 5.7 mo; HR 0.58 (0.44–0.76)
• Median OS 17.7 vs 12.0 mo; HR 0.56 (0.41–0.78)
• ORR 58.4% vs 32.3%; grade 3–4 TRAEs 24.6% vs 34.5%
• Significant PFS and OS improvement with a manageable safety profile, establishing divarasib as a new standard of care in this setting.

Ferdinandos Skoulidis

Myung-Ju Ahn · Shirish Gadgeel

Darolutamide With Androgen Deprivation Therapy (ADT) and Definitive or Salvage Locoregional Radiation Therapy (RT) for Localised, Very High-Risk Prostate Cancer: Interim Analysis of an International, Placebo-Controlled, Randomised Phase 3 Trial (DASL-HiCaP; ANZUP1801)

Phase 3 (n=1106): darolutamide vs placebo added to 96 weeks of ADT plus prostate/pelvic RT in very high-risk localized or post-prostatectomy persistent/recurrent prostate cancer. Interim analysis; median follow-up 3.8 years.

• 4-yr MFS 95% vs 88%; HR 0.42 (0.27–0.66); p=0.0001
• PSA-PFS HR 0.47 (0.33–0.67); OS HR 0.88 (0.49–1.59)
• Grade ≥3 AEs 43% vs 36%
• Darolutamide significantly improved MFS-CI; follow-up is ongoing to confirm MFS-CI surrogacy for OS.

Tamim Niazi
Sean McBride · Scott Williams · Ian Davis · Martin Stockler · Andrew Martin · Karen Bracken · Felicia Roncolato · Lisa Horvath · Shomik Sengupta · Jarad Martin · Tee Lim · Simon Hughes · Raymond McDermott · James Catto · Paul Kelly · Wendy Parulekar · Scott Morgan · Ricardo Rendon · Christopher Sweeney

Tarlatamab Plus Durvalumab vs Durvalumab as First-Line Maintenance Therapy Following Durvalumab, Platinum, and Etoposide in Extensive-Stage Small Cell Lung Cancer (ES-SCLC): Primary Analysis of the Phase 3 DeLLphi-305 Trial

Phase 3 (n=563): tarlatamab + durvalumab vs durvalumab as first-line maintenance after durvalumab + platinum–etoposide in ES-SCLC. Primary endpoint: OS.

• Median OS 21.1 vs 12.7 mo; HR 0.42 (0.32–0.54); P<0.001
• Median PFS 7.4 vs 1.9 mo; HR 0.34 (0.28–0.42); ORR 26.4% vs 4.1%
• Grade ≥3 TEAEs 46.8% vs 40.6%; CRS 49.6% (grade ≥3: 0.4%)
• Significant OS, PFS and ORR improvement, establishing tarlatamab + durvalumab as a new standard of care first-line maintenance therapy for ES-SCLC.

Jacob Sands

Perioperative Durvalumab With or Without Tremelimumab Plus Neoadjuvant Enfortumab Vedotin in Muscle-Invasive Bladder Cancer: Results From the Phase 3 VOLGA Trial

Phase 3 (n=695): perioperative durvalumab ± tremelimumab + neoadjuvant enfortumab vedotin vs control (RC, then observation or approved adjuvant therapy) in cisplatin-ineligible MIBC. Interim analysis; median EFS follow-up 22.9 mo.

• D+EV: EFS HR 0.51 (0.38–0.67); OS HR 0.58 (0.40–0.83)
• D+T+EV: EFS HR 0.61 (0.47–0.80); OS did not meet significance
• pCR 45% (D+EV) vs 10% (control); grade 3/4 TRAEs 30% and 42%
• Both EFS primary endpoints met; perioperative durvalumab plus 3 cycles of neoadjuvant EV also significantly improved OS.

Thomas Powles
Alexandra Drakaki · Jeremy Teoh · Enrique Grande · Mario Fontes-Sousa · Camillo Porta · Esther Wu · Erik Goluboff · Svetlana Ho · Stephan Hois · Ashok Gupta · James Catto

INTerpath-001: Phase 3 Study of the mRNA-Based Individualized Neoantigen Therapy Intismeran Autogene Plus Pembrolizumab vs Pembrolizumab Alone for Adjuvant Treatment of Resected Stage IIB–IV Melanoma

Double-blind phase 3 (n=1137, 2:1): mRNA individualized neoantigen therapy intismeran + pembrolizumab vs placebo + pembrolizumab, adjuvant, in resected stage IIB–IV melanoma. Median follow-up 24.6 mo.

• 24-mo RFS 82.2% vs 70.0%; HR 0.58 (0.45–0.75); P<0.001
• 24-mo DMFS 88.5% vs 80.2%; HR 0.62 (0.45–0.85); P=0.002
• Grade ≥3 AEs 23.6% vs 20.3%; pyrexia 52.2% vs 8.2%
• Significantly improved RFS and DMFS, generally well tolerated; the findings set a new benchmark for adjuvant melanoma.

Georgina Long
Jeffrey Weber · Jason Luke · Matteo Carlino · Adnan Khattak · Robert Meehan · Michelle Brown · Jinchun Zhang · Clemens Krepler · Paul Duic

FLAURA2: Analysis of On-Treatment Plasma EGFRm Dynamics and Associated Clinical Outcomes in Patients With EGFRm Advanced NSCLC Treated With First-Line Osimertinib ± Platinum–Pemetrexed

Exploratory ctDNA analysis of phase III FLAURA2: plasma EGFRm clearance (ddPCR) at Weeks 1, 2, 3 and 6 with first-line osimertinib ± platinum–pemetrexed in EGFRm advanced NSCLC.

• Week 6 clearance: 88% vs 89%
• Week 6 cleared: PFS HR 0.52 (0.36–0.76); not cleared: PFS HR 0.40 (0.16–0.97)
• Week 6 OS HR 0.73 (cleared) and 0.50 (not cleared)
• Clearance was prognostic but not predictive; osimertinib + platinum–pemetrexed was superior to osimertinib regardless of clearance status.

David Planchard

Pasi Jänne · Ying Cheng · James Yang · Noriko Yanagitani · Sang-We Kim · Shunichi Sugawara · Yan Yu · Yun Fan · Sarayut Geater · Konstantin Laktionov · Chee Lee · Natalia Valdiviezo · Samreen Ahmed · Jean-Marc Maurel · Igor Andrasina · Jonathan Goldman · Dana Ghiorghiu · Yuri Rukazenkov · Alex Todd · Kunihiko Kobayashi

A Randomized Trial of Paclitaxel ± Tovecimig in Previously Treated Patients With Advanced Biliary Tract Cancer

Randomized phase 2/3 (n=168, 2:1): tovecimig (DLL4 × VEGF-A bispecific) + paclitaxel vs paclitaxel in previously treated advanced BTC. Primary endpoint: BICR ORR.

ORR 17.1% vs 5.3% (p=0.031); median PFS 4.7 vs 2.6 mo, HR 0.44 (p<0.0001)
OS HR 1.05 (p=0.78); 54% crossed over to tovecimig + paclitaxel
Related grade ≥3 hypertension 44%; TEAEs leading to discontinuation 40% vs 15%
Significant ORR and PFS advantage; OS analysis confounded by high crossover, precluding a meaningful comparison.

Nilofer Azad

Zishuo Hu · Ilyas Sahin · Renuka Iyer · Olivia Aranha · Howard Hochster · Priyadarshini Pathak · Scott Paulson · Aparna Kalyan · Chih-Yi Liao · Nguyen Tran · Robin Kelley · Gregory Heestand · David Cosgrove · Anthony El-Khoueiry · Mitesh Borad · Nashat Gabrail · Umair Majeed · Lingling Du · Suneel Kamath · Nathan Shumway · Rachna Shroff · Lipika Goyal · Minori Rosales · Milind Javle

Results From a Phase 3 Trial of Neoadjuvant Chemotherapy Alone vs in Combination With Nivolumab Followed by Postsurgical Adjuvant Nivolumab in Patients With Muscle-Invasive Bladder Cancer (MIBC)

Phase 3 (n=653): neoadjuvant nivolumab + gemcitabine/cisplatin then adjuvant nivolumab vs neoadjuvant GC in MIBC. Primary endpoints: EFS and pCR.

EFS HR 0.94 (95.74% CI 0.71–1.25); P=0.67
pCR 39.1% vs 29.6%; OR 1.54 (99.91% CI 0.88–2.69)
OS immature: HR 0.88 (0.64–1.21); grade ≥3 TRAEs 45.9% vs 49.5%
No statistically significant differences in EFS or pCR; safety of nivolumab + GC consistent with the individual agents.

Andrea Necchi

Paired-Biopsy Multi-Omic Analysis Reveals Target-Independent Mechanisms of Antibody–Drug Conjugate (ADC) Resistance in Metastatic Breast Cancer (MBC)

Paired-biopsy multi-omic study (n=26): pre-treatment vs post-progression MBC biopsies after T-DXd, sacituzumab govitecan, or both.

T-DXd: HER2 decreased in 57%, but none became HER2-null
SG: no consistent TROP2 downregulation (5/14 up, 3/14 down)
>50% had increased efflux transporters (ABCB1, ABCC1); functional validation showed reduced payload accumulation and ADC sensitivity
ADC resistance appears driven by complex adaptations beyond target modulation, highlighting drug efflux, trafficking and cellular stress responses.

Paolo Tarantino

Final Analysis of Adjuvant Pembrolizumab in Resected Early-Stage Non–Small-Cell Lung Cancer (NSCLC): Phase 3 PEARLS/KEYNOTE-091 Study

Phase 3 (n=1177): adjuvant pembrolizumab vs placebo in resected stage IB–IIIA NSCLC. Final analysis; median follow-up 87.7 mo.

DFS HR 0.85 (0.73–0.98); median 58.7 vs 43.3 mo
OS HR 0.98 (0.81–1.18); 6-y OS 68.5% vs 66.4%
LCSS HR 0.81 (0.63–1.03); grade ≥3 AEs 34.0% vs 25.6%
Consistent DFS benefit with a favorable trend in LCSS and manageable safety; OS was not significantly improved, and the study was not powered for OS.

Mary O’Brien

Luis Paz-Ares · Sandrine Marreaud · Urania Dafni · Kersti Oselin · Libor Havel · Emilio Esteban · Dolores Isla · Alex Martinez-Marti · Martin Faehling · Masahiro Tsuboi · Jong-Seok Lee · Kazuhiko Nakagawa · Jing Yang · Ayman Samkari · Steven Keller · Murielle Mauer · Nitish Jha · Rolf Stahel · Benjamin Besse · Solange Peters

FOLFIRI Plus Ramucirumab Versus Paclitaxel Plus Ramucirumab as Second-Line Therapy for Taxane-Pretreated Patients With Advanced or Metastatic Gastroesophageal

Adenocarcinoma: Final Results of the Phase III IKFs602/AIO RAMIRIS Study

Phase III (n=317): FOLFIRI + ramucirumab vs paclitaxel + ramucirumab, second-line, in taxane-pretreated advanced GEA. Co-primary endpoints: OS and ORR.
Median OS 8.7 vs 7.5 mo; HR 0.95; p=.33
ORR 25.3% vs 22.6% (p=.29); median PFS 5.5 vs 3.7 mo, HR 0.7 (p=.003)
Grade 3–5 AEs 70% vs 68%
Co-primary endpoints were not met; PFS was clearly improved, supporting personalized treatment decisions in taxane-pretreated advanced GEA.

Magdalena Scheck

Final Protocol-Prespecified Analysis of the Phase 3 KEYNOTE-564 Trial of Adjuvant Pembrolizumab Versus Placebo in Clear Cell Renal Cell Carcinoma (ccRCC)

Phase 3 (n=994): adjuvant pembrolizumab vs placebo after nephrectomy in ccRCC at high risk of recurrence. Final prespecified analysis; median follow-up 85.9 mo.

DFS HR 0.68 (0.56–0.82); 7-yr DFS 57.2% vs 44.6%
OS HR 0.70 (0.53–0.92); 7-yr OS 82.3% vs 76.6%
No new serious treatment-related AEs
DFS and OS benefits remained consistent with earlier reports, supporting adjuvant pembrolizumab as standard treatment for ccRCC at increased risk of recurrence.

Toni Choueiri

Naomi Haas · Thomas Powles · Piotr Tomczak · Se Hoon Park · Balaji Venugopal · Stefan Symeonides · Thomas Ferguson · Yen-Hwa Chang · Jae-Lyun Lee · Piotr Sawrycki · Naveed Sarwar · Howard Gurney · Marine Gross-Goupil · John Burke · Gurjyot Doshi · Jerry Cornell · Joseph Burgents · Rodolfo Perini

OncoAlert 4Sight, #ESMO2026

Retrospective Exploratory Biomarker Analyses From evERA Breast Cancer: A Phase III Trial of Giredestrant + Everolimus in Patients With Oestrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer in the Post-CDK4/6 Inhibitor Setting

Exploratory biomarker analysis of phase III evERA (365 ctDNA-evaluable): giredestrant + everolimus vs SOC endocrine therapy + everolimus in post-CDK4/6i ER+, HER2– aBC.
PFS HR 0.52 (0.39–0.70) with cTF ≥1%; 0.61 (0.40–0.94) with cTF <1%
ESR1m: PFS HR 0.58 (D538) and 0.35 (Y537)
TP53m PFS HR 0.65 (0.45–0.93); PIK3CAm 0.55 (0.36–0.83)
Giredestrant + everolimus maintained greater PFS benefit regardless of cTF status, with benefit across all ESR1 variants and poor prognostic subgroups.

Sara Tolaney

OncoAlert 4Sight, #ESMO2026

Tarlatamab in Previously Treated SCLC: Extended Follow-Up of Overall Survival From the Phase 3 DeLLphi-304 Trial

Phase 3 (n=509): tarlatamab vs chemotherapy (topotecan, lurbinectedin or amrubicin) in SCLC after first-line platinum-based chemotherapy. Primary endpoint: OS; median follow-up 23 mo.
Median OS 13.6 vs 8.4 mo; HR 0.62 (0.51–0.76); 18-mo OS 42% vs 24%
Baseline brain metastases subgroup: OS HR 0.52 (0.38–0.70)
Grade ≥3 TRAEs 28% vs 63%
Durable survival benefit with a manageable safety profile and no new safety signals, reinforcing tarlatamab as standard of care after first-line platinum-based chemotherapy.

Charles Rudin

Giannis Mountzios · Longhua Sun · Byoung Chul Cho · Umut Demirci · Sofia Baka · Mahmut Gümüş · Antonio Lugini · Bo Zhu · Yan Yu · Ippokratis Korantzis · Ji-Youn Han · Tudor-Eliade Ciuleanu · Myung-Ju Ahn · Pedro Rocha · Julien Mazières · Sally Lau · Martin Schuler · Fiona Blackhall · Tatsuya Yoshida · Taofeek Owonikoko · Luis Paz-Ares · Tony Jiang · Ali Hamidi · Diana Gauto · Gonzalo Recondo

OncoAlert 4Sight, #ESMO2026

Phase 3 LEAP-012 Study of Lenvatinib + Pembrolizumab vs Dual Placebo With Transarterial Chemoembolization (TACE) for Unresectable Non-Metastatic Hepatocellular Carcinoma: Long-Term OS Results

Phase 3 (n=480): lenvatinib + pembrolizumab + TACE vs dual placebo + TACE in unresectable, non-metastatic HCC. Dual primary endpoints: PFS and OS. Long-term OS (IA3).
Median OS 40.4 vs 40.8 mo; HR 0.98 (0.76–1.26)
Median PFS 14.6 vs 10.2 mo; HR 0.70 (0.56–0.89)
Grade ≥3 TRAEs 72.2% vs 32.0%
LEAP-012 met its primary endpoint for PFS but did not show OS benefit; a median OS of ~40 mo sets a new benchmark for trial design.

Josep Llovet

Masatoshi Kudo · Zhenggang Ren · Yabing Guo · Guohong Han · Hailan Lin · Jinfang Zheng · Sadahisa Ogasawara · Ji Hoon Kim · Haitao Zhao · Chuan Li · David Madoff · Mark Ghobrial · Tomokazu Kawaoka · René Gerolami · Masafumi Ikeda · Hiromitsu Kumada · Anthony El-Khoueiry · Arndt Vogel · Xiang Peng · Kalgi Mody · Corina Dutcus · Leonid Dubrovsky · Abby Siegel · Richard Finn

OncoAlert 4Sight, #ESMO2026

Long-Term Overall Survival With Abiraterone Acetate Plus Prednisone in the PEACE-1 Phase 3 Trial for De Novo Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Phase 3, 2×2 factorial (n=1173): abiraterone and/or prostate RT added to SOC (ADT ± docetaxel) in de novo mCSPC. Median follow-up 7.7 y.
Abiraterone: OS HR 0.75 (0.65–0.87); p=0.0001
ADT + docetaxel ± abiraterone: median OS 4.4 vs 6.2 y; 8-year OS 27.1% vs 40.3%
High-volume: 8-year OS 20% vs 38%; interaction by metastatic extent p=0.56
Major OS benefit of adding abiraterone to SOC, irrespective of metastatic extent; triplet associated with almost twice as many long-term survivors in some subgroups.

Karim Fizazi

Stéphanie Foulon · Joan Carles · Guilhem Roubaud · Ray McDermott · Aude Fléchon · Bertrand Tombal · Stéphane Supiot · Dominik Berthold · Philippe Ronchin · Gabriel Kacso · Gwenaëlle Gravis · Fabio Calabro · Jean-François Berdah · Ali Hasbini · Marlon Silva · Antoine Thiery-Vuillemin · Igor Latorzeff · Loïc Mourey · Brigitte Laguerre · Sophie Abadie-Lacourtoisie · Etienne Martin · Claude El Kouri · Anne Escande · Alvar Rosello · Nicolas Magne · Friederike Schlurmann · Frank Priou · Marie-Eve Chand-Fouche · Salvador Villà Freixa · Muhammad Jamaluddin · Isabelle Rieger · Alberto Bossi

OncoAlert 4Sight, #ESMO2026

BRIDGET: A Phase II Trial of Tucatinib Added to Trastuzumab/Pertuzumab or Ado-Trastuzumab Emtansine After Isolated Intracranial Progression in Patients With Advanced HER2-Positive Breast Cancer

Single-arm phase II (47 evaluable): tucatinib added to ongoing HP or T-DM1 after SRS for isolated intracranial progression in HER2+ MBC. Primary endpoint: iPFS (RANO-BM).
Median iPFS not reached; p<0.0001 vs historical median of 5 mo
iPFS 91% at 6 mo, 64% at 12 mo, 59% at 18 mo
Grade ≥3 AEs 15%; extracranial progression 4.3%
Adding tucatinib to HP after radiation met the primary endpoint, with more than half of patients free of intracranial progression at 18 months.

Sarah Sammons

Amanda Van Swearingen · Laura Noteware · Nusayba Bagegni · Kelly Moulton · Stevie Threatt · Denise Jaggers · Shannon Shea · Eric Lipp · Erin Riley · Sin-Ho Jung · Gloria Broadwater · Masey Ross · Kimberly Strickland · Sasha Beyer · Alison Conlin · Aki Morikawa · Rashmi Murthy · Carey Anders

OncoAlert 4Sight, #ESMO2026

Primary Results of SARON: A Randomised-Controlled Trial of Consolidation Radiotherapy for Synchronous Oligometastatic Non-Small Cell Lung Cancer

Randomized phase II (n=140): first-line SACT ± consolidation radiotherapy in synchronous oligometastatic AGA-negative NSCLC. Endpoints: OS and PFS.
Median OS 31.0 vs 28.0 mo; HR 0.99 (0.63–1.55); p=0.95
Median PFS 13.9 vs 8.9 mo; HR 0.64 (0.43–0.95); p=0.03
12-month local failure 13.0% vs 39.5% (p<0.01); grade ≥3 AEs 28.6% in both arms
SACT + RT achieved better local disease control and longer PFS with acceptable side effects, but this did not translate into survival benefit.

Fiona McDonald

Watch-and-Wait Strategy for Dostarlimab in Localized dMMR/MSI-H Gastroesophageal Adenocarcinoma: Results From the First Interim Analysis of the GERCOR-GONO DEWI Phase II Study

Phase II, first interim analysis (24 evaluable patients): dostarlimab with a watch-and-wait strategy in localized dMMR/MSI-H gastroesophageal adenocarcinoma. Primary endpoint: 1-year cCR without surgery.

1-year cCR: 62.5% (15/24)
No relapse or death in patients with 1-year cCR (median follow-up 16.20 mo)
Grade 3–4 dostarlimab-related AEs: 21%; 9/24 underwent surgery, all R0
Dostarlimab led to a 62.5% 1-year cCR at the first interim analysis, enabling organ preservation.

Thierry André
Christelle de la Fouchardière

OncoAlert 4Sight, #ESMO2026

Perioperative Pembrolizumab or Placebo + Neoadjuvant Cisplatin and Gemcitabine in Muscle-Invasive Bladder Cancer: The Double-Blind, Phase 3 KEYNOTE-866 Study

Phase 3, double-blind (n=907): perioperative pembrolizumab or placebo + neoadjuvant gemcitabine-cisplatin and RC + PLND in cisplatin-eligible MIBC. Primary endpoint: EFS.
Median EFS 74.1 mo vs NR; HR 0.88 (0.71–1.10); P=.1366
pCR 44.4% vs 35.8%; OS HR 1.00 (0.79–1.27); neither formally tested
Grade 3–5 TEAEs 80.2% vs 75.1%
Perioperative pembrolizumab did not confer a statistically significant EFS benefit; safety profile manageable and consistent with prior reports.

Jens Bedke

Arlene Siefker-Radtke · Gary Steinberg · Hiroyuki Nishiyama · Xiao Fang · Ritesh Kataria · Blanca Homet Moreno · Christopher Hoimes

OncoAlert 4Sight, #ESMO2026

Efficacy and Safety of Atirmociclib + Fulvestrant in Patients With HR+/HER2– Advanced/Metastatic Breast Cancer Who Progressed on Prior CDK4/6 Inhibitor in a Randomized Phase 2 Study (FOURLIGHT-1)

Randomized phase 2 (n=263): atirmociclib + fulvestrant vs investigator’s choice (fulvestrant or everolimus + exemestane) in HR+/HER2– mBC after prior CDK4/6i. Primary: investigator-assessed PFS.

Median PFS 9.4 vs 6.6 mo; HR 0.60 (0.440–0.825); 1-sided p=0.0007
ORR in patients with measurable disease: 19.3% vs 11.3%; CBR: 61.9% vs 46.0%
Atirmociclib discontinuation due to TRAEs: 4.0%; most common TRAE neutropenia (46.4%)
First next-generation CDKi to show significant and clinically meaningful PFS improvement after prior CDK4/6i, with a manageable safety profile.

Antonio Giordano

OncoAlert 4Sight, #ESMO2026

Pembrolizumab With or Without Platinum-Based Chemotherapy as First-Line Treatment in Advanced NSCLC With PD-L1 ≥50%: PERSEE Phase 3 Trial (GFPC 01-2020)

Phase 3, open-label (n=321): pembrolizumab + platinum-based chemotherapy vs pembrolizumab alone, first-line advanced NSCLC with PD-L1 ≥50%. Primary endpoint: PFS by blinded central review.

Median PFS 16.1 vs 6.9 mo; HR 0.56 (0.43–0.74); p<0.001
Median OS 50.2 vs 29.9 mo; HR 0.77 (0.57–1.05); ORR 77.5% vs 50.3%
Grade ≥3 TRAEs 53.8% vs 19.3%
Pembrolizumab-chemotherapy significantly improved PFS vs pembrolizumab monotherapy and may help refine treatment selection.

Chantal Decroisette

Renaud Descourt · Christos Chouaid · Maurice Pérol · Benjamin Besse · Laurent Greillier · Olivier Bylicki · Charles Ricordel · Florian Guisier · Radj Gervais · Roland Schott · Jean-Bernard Auliac · Gilles Robinet

OncoAlert 4Sight, #ESMO2026

First-Line Pembrolizumab + Lenvatinib + Belzutifan or MK-1308A + Lenvatinib in Advanced RCC: The Randomized Open-Label Phase 3 LITESPARK-012 Study

Phase 3 (n=1688), untreated advanced ccRCC: pembrolizumab + lenvatinib + belzutifan (Arm A) or MK-1308A + lenvatinib (Arm B) vs pembrolizumab + lenvatinib. Dual primary: PFS by BICR and OS.

Arm A: PFS HR 1.08 (0.93–1.26); OS HR 1.04 (0.87–1.25)
Arm B: PFS HR 1.07 (0.92–1.25); OS HR 1.12 (0.94–1.35)
Discontinuation due to AEs: 51.6% (A), 51.4% (B), 36.2% (control)
Neither belzutifan nor CTLA-4 blockade added to pembrolizumab + lenvatinib improved efficacy; pembrolizumab + lenvatinib remains a 1L SOC.

Toni Choueiri

Thomas Powles · Martin Voss · Elizabeth Plimack · Howard Gurney · Yue Song · Rodolfo Perini · Karla Rodriguez-Lopez · Brian Rini

OncoAlert 4Sight, #ESMO2026

Final Overall Survival Analysis of postMONARCH: Abemaciclib Plus Fulvestrant After Progression on Prior CDK4/6 Inhibitor in HR+, HER2– Advanced Breast Cancer

Phase 3, double-blind trial (n=368): abemaciclib or placebo plus fulvestrant in HR+, HER2– ABC after progression on prior CDK4/6i + ET. Final OS analysis.

Median OS 32.1 vs 24.6 mo; HR 0.80 (0.60–1.06); p=0.1145, statistical significance not reached
Updated PFS HR 0.78 (0.62–0.99); nominal p=0.0390
Safety consistent with the established abemaciclib profile; no new signals
Numerically longer median OS, not statistically significant. While absolute PFS benefit was modest, overall evidence supports considering abemaciclib-based treatment after disease progression on prior CDK4/6i + ET.

Kevin Kalinsky

Giampaolo Bianchini · Erika Hamilton · Stephanie Graff · Kyong Hwa Park · Rinath Jeselsohn · Umut Demirci · Miguel Martin · Rachel Layman · Sara Hurvitz · Sarah Sammons · Peter Kaufman · Montserrat Muñoz · Jiun-I Lai · Holly Knoderer · Cynthia Sandoval · Aarti Chawla · Bastien Nguyen · Yanhong Zhou · Elizabeth Ravenberg · Lacey Litchfield · Lillian Smyth · Seth Wander

OncoAlert 4Sight, #ESMO2026

Pembrolizumab or Placebo Plus Concurrent Definitive Chemoradiotherapy in Esophageal and Gastroesophageal Junction (GEJ) Cancer: The Phase 3 Randomized KEYNOTE-975 Study

Phase 3, double-blind trial (n=703): pembrolizumab or placebo plus definitive chemoradiotherapy in untreated, unresectable esophageal/GEJ cancer. Dual primary endpoints: EFS and OS.

CPS ≥10 EFS: median 15.2 vs 14.7 mo; HR 0.97 (0.77–1.23); P=0.3994
CPS ≥10 OS: median 32.2 vs 35.0 mo; HR 1.00 (0.77–1.30); nominal P=0.5003
Grade 5 AEs 13% vs 10%; discontinuation due to AEs 34% vs 27%
Pembrolizumab + dCRT did not significantly improve EFS in PD-L1 CPS ≥10; no new safety signals observed.

Manish Shah

Jaafar Bennouna · Toshihiko Doi · Lin Shen · Ken Kato · Antoine Adenis · Harvey Mamon · Markus Moehler · Xiaolong Fu · Byoung Chul Cho · Sonal Bordia · Pooja Bhagia · Chie-Schin Shih · Anjali Desai · Peter Enzinger

OncoAlert 4Sight, #ESMO2026
Final Analysis of the GIM3 FATA Trial: Treatment Schedule and Three Aromatase Inhibitors in Postmenopausal HR+ Early Breast Cancer

Randomized trial (n=3697): 5 years of anastrozole, exemestane or letrozole, upfront or after 2 years of tamoxifen. Co-primary: DFS by schedule and by AI.

Upfront vs switch: DFS HR 0.95 (0.82–1.09); OS HR 0.88 (0.74–1.06)
10-year DFS 79.1% anastrozole, 76.6% letrozole, 74.2% exemestane (global p=0.028)
Exemestane vs anastrozole: adjusted DFS HR 1.23 (1.04–1.46). 10-year OS across AIs: no statistically significant difference (p=0.25)
No schedule superior; exemestane associated with worse DFS. Choice should be individualized by tolerability, comorbidities and cost.

Pietro De Placido

Laura Arenare · Erica Pietroluongo · Giancarlo Bisagni · Maria Sarobba · Antonio Russo · Ferdinando Riccardi · Lucia Del Mastro · Antonio Pazzola · Francesco Cognetti · Jennifer Foglietta · Stefania Gori · Francesco Nuzzo · Adriano Gravina · Michelino De Laurentiis · Roberto Bianco · Grazia Arpino · Sabino De Placido · Ciro Gallo · Francesco Perrone