AiomNews N. 1039, 3 Marzo 2026

Oggi in Oncologia

Palbociclib for Hormone-Receptor-Positive, HER2-Positive Advanced Breast Cancer

Background: Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies … (leggi tutto)

Il trial PATINA affronta una delle domande biologicamente più coerenti ma finora non definitivamente risolte nel carcinoma mammario HER2+/HR+: il blocco simultaneo di HER2, recettore estrogenico e asse CDK4/6 può prolungare significativamente il controllo di malattia nella fase di mantenimento?
In questo studio di fase III, l’aggiunta di palbociclib alla terapia di mantenimento con anti-HER2 ed endocrina ha determinato un prolungamento significativo della PFS (44,3 vs 29,1 mesi; HR 0,75; p=0,02), con un follow-up mediano superiore a 4 anni. Si tratta di una delle mediane di PFS più lunghe mai riportate in questo setting.
Il razionale è solido: l’interazione tra pathway HER2 e segnale estrogenico, insieme al ruolo centrale dell’asse ciclina D–CDK4/6 nella resistenza, giustifica un approccio triplice. PATINA dimostra che tale strategia non è solo teoricamente valida, ma clinicamente efficace.
Il prezzo è rappresentato dalla tossicità ematologica: eventi avversi di grado 3–4 significativamente più frequenti nel braccio palbociclib (neutropenia predominante).Tuttavia, il profilo di sicurezza è coerente con quanto noto per palbociclib e appare gestibile con monitoraggio adeguato.
Rimangono interrogativi importanti: l’impatto su overall survival (analisi ancora in corso), la selezione delle pazienti che maggiormente beneficiano (biomarcatori?), e l’integrazione con le nuove opzioni come T-DXd e tucatinib. Inoltre, la complessità terapeutica e i costi richiederanno valutazioni di sostenibilità.
PATINA potrebbe tuttavia segnare un cambio di paradigma nel sottogruppo HER2+/HR+, sottolineando che non tutte le malattie HER2-positive sono biologicamente sovrapponibili. La personalizzazione all’interno del fenotipo HER2+ diventa sempre più necessaria.

Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC

Triple-negative breast cancer (TNBC) is frequently associated with metastatic relapse, even at an early stage¹. Here we assessed an individualized neoantigen mRNA vaccine in 14 patients with TNBC following surgery and after neoadjuvant or adjuvant therapy. In peripheral blood of nearly all patients, high-magnitude, vaccine-induced, mostly de novo T cell responses to multiple neoantigens were detected that remained … (leggi tutto)

Il carcinoma mammario triplo negativo (TNBC) rappresenta ancora oggi una delle sfide più complesse dell’oncologia mammaria. Nonostante i progressi ottenuti con chemioterapia, immunoterapia e più recentemente con gli anticorpi farmaco-coniugati, il rischio di recidiva rimane significativo, in particolare nei primi tre anni dalla diagnosi. La necessità di strategie capaci di consolidare la risposta ottenuta con i trattamenti standard in fase precoce è quindi evidente.
In questo contesto si inserisce il recente studio pubblicato su Nature che ha valutato la fattibilità e l’immunogenicità di un vaccino personalizzato a mRNA diretto contro neoantigeni tumorali in pazienti con TNBC in setting adiuvante.
Un approccio realmente “su misura”.
Il principio è quello della medicina ultra-personalizzata: attraverso il sequenziamento del tumore di ciascuna paziente vengono identificare mutazioni somatiche in grado di generare neoantigeni, cioè nuove sequenze proteiche riconoscibili dal sistema immunitario. Le mutazioni selezionate vengono poi codificate in un vaccino a mRNA, formulato in nanoparticelle lipidiche, somministrato per via endovenosa.
Nel trial TNBC-MERIT, 14 pazienti trattate con intento curativo (dopo chirurgia e terapia standard neo/adiuvante) hanno ricevuto un vaccino contenente fino a 20 neoantigeni individuali. L’obiettivo primario non era dimostrare efficacia clinica, bensì verificare sicurezza, fattibilità produttiva e capacità di indurre risposte immunitarie specifiche.

Risposte T robuste e durature
Il dato più rilevante è che tutte le pazienti hanno sviluppato una risposta immunitaria T-specifica contro uno o più neoantigeni vaccinali. In oltre l’85% dei casi le risposte sono state di elevata intensità, spesso policlonali e dirette contro molteplici target mutazionali.
Ancora più interessante è la durabilità: le cellule T neoantigene-specifiche sono rimaste rilevabili nel sangue periferico per anni, in alcuni casi fino a sei anni dopo la vaccinazione. L’analisi fenotipica ha documentato la coesistenza di due sottopopolazioni chiave:
• cellule effettrici citotossiche “pronte all’azione”;
• cellule con fenotipo memory stem-like (TCF-1+, IL7R+), potenzialmente in grado di auto-rinnovarsi e sostenere nel tempo la risposta immunitaria.
Questo aspetto è particolarmente rilevante in un setting adiuvante, dove l’obiettivo è prevenire la ricrescita di micrometastasi residue.

Segnali clinici e meccanismi di escape
Con un follow-up mediano di circa 5 anni, la maggior parte delle pazienti è rimasta libera da recidiva. Tuttavia, lo studio non era randomizzato né comparativo, quindi non consente conclusioni sull’efficacia clinica.
I casi di recidiva hanno fornito però spunti biologici interessanti. In una paziente la risposta immunitaria era stata debole; in un’altra si è osservata una perdita di espressione di MHC di classe I nel tumore recidivato, suggerendo un meccanismo di escape immunologico. In un terzo caso, la recidiva derivava da un secondo tumore primitivo geneticamente distinto, non rappresentato nel disegno vaccinale.

Questi dati confermano che, se da un lato la risposta immunitaria può essere potente e persistente, dall’altro la pressione selettiva può favorire meccanismi di evasione, aprendo la strada a strategie combinate (es. checkpoint inhibitors o approcci capaci di ripristinare la presentazione antigenica).
Quale spazio nella pratica clinica?
Siamo ancora in una fase esplorativa. Le principali limitazioni dello studio sono il numero ridotto di pazienti e l’assenza di un braccio di controllo. Tuttavia, il messaggio è chiaro: la tecnologia è fattibile in tempi compatibili con la pratica clinica, è sicura e soprattutto è in grado di indurre una risposta immunitaria policlonale, robusta e duratura anche in un tumore a carico mutazionale medio-basso come il TNBC.
Nel panorama attuale, in cui l’immunoterapia è già parte integrante del trattamento del TNBC precoce ad alto rischio, l’integrazione di un vaccino personalizzato potrebbe rappresentare un passo ulteriore verso un’immunoterapia realmente “curativa”, mirata a eradicare la malattia minima residua.
La sfida dei prossimi anni sarà dimostrare, in studi randomizzati, che questa potente risposta immunologica si traduca in un reale beneficio in termini di sopravvivenza libera da malattia e, soprattutto, di guarigione.

In Europe

No OS Improvement with CDK4/6 Inhibitors Used in First- Compared with Second-Line Treatment in Patients with HR-positive, HER2-negative ABC

Mar 03, 2026 – In an open-label, investigator-initiated randomised phase III SONIA study, conducted in 74 Dutch hospitals, that compared the sequence of an aromatase inhibitor (AI) plus CDK4/6 inhibitor as first-line treatment followed by fulvestrant as second-line treatment (CDK4/6 inhibitor first-line group) versus the sequence of an AI as first-line treatment followed by fulvestrant plus CDK4/6 inhibitor as second-line treatment ... (leggi tutto)

Antitumour Activity of Rezatapopt Provides Proof of Concept for p53 Reactivation in Patients with TP53 Y220C-mutated Solid Tumours

Mar 02, 2026 – Rezatapopt is an investigational, first-in-class, oral, selective small molecule p53 reactivator that binds specifically to Y220C-mutated p53. In a phase I, single-group, multicentre, dose-escalation and dose-optimisation PYNNACLE study, rezatapopt activity was assessed in heavily pretreated patients with locally advanced or metastatic solid tumours harbouring a TP53 Y220C mutation ... (leggi tutto)

First combined COVID-19 and influenza vaccine for people 50 years and older

Feb 27, 2026 – EMA has recommended granting a marketing authorisation in the European Union (EU) for mCombriax, a messenger RNA vaccine for protecting people aged 50 years and older against COVID-19 and seasonal influenza (flu).
COVID-19 and influenza are infectious illnesses that mainly affect the respiratory system, causing symptoms such as cough and nasal congestion, as well as systemic symptoms like fever and chills ... (leggi tutto)

EMA Recommends Extension of Therapeutic Indications for Ponatinib

Feb 27, 2026 – On 29 January 2026, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product ponatinib (Iclusig).
The marketing authorisation holder for this medicinal product is Incyte Biosciences Distribution B.V.
The CHMP adopted a new indication as follows ... (leggi tutto)

Screening Programme by Primary Colonoscopy or Two Rounds of Two-Stool FIT Detects More Lower-Stage CRCs than Usual Care

Feb 26, 2026 – In assessment of the diagnostic phase of the randomised controlled Screening of Swedish Colons (SCREESCO) study, there was an increase of stage I-II colorectal cancer (CRC) incidence in the intervention arms compared to usual care, particularly during the first year after randomisation when most of the screening colonoscopies were performed. More stage I-II and fewer stage III-IV CRCs were diagnosed in the intervention arms (primary colonoscopy screening arm and two rounds of a two-stool faecal immunochemical testing ... (leggi tutto)

FDA Approves Pembrolizumab with Paclitaxel for Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma

Feb 25, 2026 – On 10 February 2026, the US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda, Merck) as well as pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex, Merck) in combination with paclitaxel, with or without bevacizumab, for adult patients with platinum-resistant epithelial ovarian, Fallopian tube, or primary peritoneal carcinoma whose tumours express PD-L1 combined positive score (CPS) ≥1 as determined by an FDA-authorised test, and who have received one or two prior systemic treatment regimens ... (leggi tutto)

Nivolumab Plus Chemotherapy Continues to Demonstrate Long-Term Survival Benefits in Patients with Gastric, GEJ and Oesophageal Adenocarcinoma

Feb 24, 2026 – CheckMate 649 is the first clinical trial to report 5-year follow-up data of a PD1 inhibitor in combination with chemotherapy as a first-line treatment for patients with advanced gastric, gastro-oesophageal junction (GEJ), and oesophageal adenocarcinoma. Long-term efficacy with nivolumab plus chemotherapy versus chemotherapy was maintained with 5 years of follow-up, including clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS) ... (leggi tutto)

Mar 01, 2026 – Zongertinib received February 2026 FDA accelerated first-line approval for HER2 TKD–mutated NSCLC, showing a 76% response rate and manageable tolerability. Beamion LUNG-02 is the confirmatory trial and currently enrolling.
LITESPARK-022 demonstrated adjuvant belzutifan plus pembrolizumab improved DFS in post-nephrectomy ccRCC (HR, 0.72), with median DFS unreached and higher but acceptable toxicity and low discontinuations ... (leggi tutto)

Feb 28, 2026 – Accelerated approval covers unresectable/metastatic nonsquamous NSCLC with HER2 (ERBB2) TKD activating mutations, contingent on detection by an FDA-authorized companion diagnostic.
Commissioner’s National Priority Review Voucher pilot participation enabled expedited review pathways for therapies positioned to address defined national priorities ... (leggi tutto)

FDA Grants Accelerated Approval to Zongertinib for Unresectable or Metastatic, Nonsquamous NSCLC With HER2 TKD Mutations

Feb 26, 2026 – Accelerated approval covers unresectable/metastatic nonsquamous NSCLC with HER2 (ERBB2) TKD activating mutations, contingent on detection by an FDA-authorized companion diagnostic.
Commissioner’s National Priority Review Voucher pilot participation enabled expedited review pathways for therapies positioned to address defined national priorities ... (leggi tutto)

FDA Grants Full Approval to Encorafenib Plus Cetuximab/Chemotherapy for BRAF V600E+ mCRC

Feb 24, 2026 – Traditional approval covers encorafenib plus cetuximab with fluorouracil-based chemotherapy for adult BRAF V600E–mutant mCRC, requiring mutation detection via an FDA-approved companion diagnostic test.
BREAKWATER arm B achieved ORR 61% versus 40% with chemotherapy ± bevacizumab (P = .0008), supporting superior antitumor activity with the targeted doublet plus mFOLFOX6 ... (leggi tutto)

LITESPARK-022 Results Show DFS Benefit, Support the Addition of Belzutifan to Adjuvant Pembrolizumab in High-Risk ccRCC

Feb 28, 2026 – LITESPARK-022 is a randomized phase 3 trial comparing 1 year of pembrolizumab plus belzutifan versus pembrolizumab alone in patients with clear cell renal cell carcinoma (ccRCC) at increased risk for recurrence after nephrectomy.
Adding belzutifan to pembrolizumab yielded a 28% reduction in the risk of disease recurrence or death, making it the first adjuvant phase 3 trial in RCC to show a significant benefit for a combination therapy versus an active immunotherapy comparator … (leggi tutto)

SWOG S-1602 Analysis Suggests Tokyo-172 Strain of BCG Is Noninferior to TICE Strain in the Treatment of NMIBC

Feb 27, 2026 – A comparison of efficacy outcomes from 2 Bacillus Calmette-Guérin (BCG) strains for the treatment of non–muscle-invasive bladder cancer (NMIBC) found that the Tokyo-172 strain is noninferior to the standard-of-care TICE strain, according to data from the phase 3 SWOG S-1602 trial.
Notably, the 5-year high-grade recurrence-free survival (HG RFS) for the Tokyo-172 strain was 64% versus 58% for the TICE strain, and the 5-year progression-free survival (PFS) was 79% versus 79%, respectively … (leggi tutto)

Perioperative Enfortumab Vedotin + Pembrolizumab Improves Clinical Outcomes, DFS Compared With Surgery Alone in MIBC

Feb 27, 2026 – A follow-up study to the KEYNOTE-905/EV-303 trial found that patients who received enfortumab vedotin plus pembrolizumab in addition to radical cystectomy with pelvic lymph node dissection had better pathologic outcomes and longer disease-free survival (DFS) than patients who received surgery alone … (leggi tutto)

KEYNOTE-B15: Enfortumab Vedotin Plus Pembrolizumab Improves OS, EFS, pCR Rates Over Chemotherapy in MIBC

Feb 27, 2026 – According to results of the phase 3 KEYNOTE-B15 study, the combination of enfortumab vedotin (EV) plus pembrolizumab before and after radical cystectomy yields significantly improved outcomes over gemcitabine plus cisplatin followed by cystectomy in patients with muscle-invasive bladder cancer (MIBC).
The primary endpoint of event-free survival (EFS) by blinded independent central review favored the EV plus pembrolizumab group. The median EFS was not … (leggi tutto)

Cancer Diagnoses During COVID-19 Pandemic: Impact on 1-Year Cause-Specific Survival

Feb 26, 2026 – In a study reported in JAMA Oncology, Burus et al found that patients diagnosed with invasive cancer during 2020 and 2021—the first 2 years of the COVID-19 pandemic—had poorer 1-year cause-specific survival (CSS) rates vs patients diagnosed in the prepandemic years of 2015 to 2019 … (leggi tutto)

New First-Line Targeted Therapy Recommendations Among Updated ASCO Guidance on Gastroesophageal Cancer Management

Feb 26, 2026 – ASCO has released a guideline update addressing advances in the use of immunotherapy and targeted therapy for the treatment of advanced gastroesophageal cancer, particularly in the first-line setting.
One notable new recommendation involves the early use of predictive biomarker testing in patients with gastroesophageal adenocarcinoma, including testing for PD-L1 expression, deficient mismatch repair/microsatellite instability–high, HER2, and claudin 18.2 (CLDN18.2) … (leggi tutto)

Combination Enzalutamide and Radium-223 Extends OS in Bone-Dominant mCRPC in Phase 3 Trial

Feb 26, 2026 – The combination of enzalutamide and up to 6 cycles of radium-223 yielded a significant overall survival (OS) benefit (HR 0.76) over enzalutamide alone in a phase 3 trial of 466 patients with metastatic castration-resistant prostate cancer (mCRPC), at a median of 38.2 versus 32.6 months.
Improvement in radiographic progression-free survival (rPFS) with the combination was confirmed in 2025 and again in final results (median 19.2 vs 16.4 months) … (leggi tutto)

Adding Hormone Therapy to Postoperative Radiotherapy Confers a Survival Benefit in Patients With Prostate Cancer and High PSA

Feb 26, 2026 – The POSEIDON study, a meta-analysis of individual patient data from 6 phase 3 randomized trials, examined whether patients with prostate cancer benefit from the addition of hormone therapy to post-operative radiotherapy (PORT) after radical prostatectomy.
The addition of hormone therapy did not improve survival in the overall patient population, the study found. However, there was an improvement in overall survival (OS) for patients with a prostate-specific antigen (PSA) level above 0.5 ng/mL at the time of radiation therapy … (leggi tutto)

A Decade of Research Leads to New Guidance on Using Colony-Stimulating Factors in Anticancer Treatment

Feb 25, 2026 – ASCO has published an updated guideline to apprise oncologists of the latest evidence on the use of hematopoietic colony-stimulating factors (CSFs) to support anticancer treatment, namely chemotherapy and stem cell transplantation.
A strong research base has emerged from more than a decade of randomized controlled trials and systematic reviews on CSFs, including investigations into 2 novel drugs (eflapegrastim and efbemalenograstim) and additional data on filgrastim and pegfilgrastim biosimilars.? … (leggi tutto)

Weighing Cost and Clinical Outcomes in Treatment Decision-Making: Analysis Offers Insights Into Cabazitaxel Versus Lu-PSMA in mCRPC

Feb 25, 2026 – A cost-consequent analysis of a 100-patient cohort with metastatic castration-resistant prostate cancer (mCRPC) who were covered by Medicare and previously treated with docetaxel and an androgen receptor pathway inhibitor (ARPI) found that cabazitaxel costs approximately one-third as much the prostate-specific membrane antigen Lutetium-177 vipivotide tetraxetan (Lu-PSMA), yielding a per-patient cost difference of approximately $194,000 at 18 months … (leggi tutto)

Staining of Oncogenic Biomarkers in Cervical Cells Improves Cervical Cancer Risk Triage for Women Testing Positive for HPV

Feb 25, 2026 – Among women testing positive for HPV, positive staining of biomarkers p16 and Ki-67 on cervical cells (also known as dual-stain) had a 9.4% baseline risk of grade 3 or higher cervical intraepithelial neoplasia (CIN3+) compared with 0.8% for women with negative testing.
Over 5 years, risk of CIN3+ was consistently higher with dual-stain positivity (14.0%) and lower with negativity (2.3%) compared with positive and negative findings on cytology only at 9.7% and 5.5%, respectively … (leggi tutto)

Pillole dall’AIFA
2 marzo 2026 – Aggiornamento degli elenchi dei farmaci innovativi e degli agenti antinfettivi al 31/01/2026
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27 febbraio 2026 – Aggiornamento “Diario di bordo sulla Trasparenza”
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27 febbraio 2026 – AIFA sostiene la giornata delle malattie rare 2026
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26 febbraio 2026 – Duchenne e mieloma multiplo: il SSN rimborsa due terapie innovative
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24 febbraio 2026 – Tabelle farmaci di classe A e H al 30/09/2025
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