Oggi in Oncologia
Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator’s Choice in Chemorefractory KRAS G12C Colorectal Cancer
In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator’s choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator’s choice … (leggi tutto)
L’adenocarcinoma colo-rettale (CCR) è tuttora uno dei tumori più diffusi e a più elevata mortalità.
Il trial CodeBreaK 300 ha già dimostrato come la combinazione di sotorasib e panitumumab aumenti il tasso di risposta e raddoppi la PFS rispetto alla terapia scelta dallo sperimentatore (trifluridina/tipiracil o regorafenib) in pazienti pretrattati con CCR metastatico KRAS G12C mutato.
L’analisi secondaria dello studio in oggetto recentemente pubblicata, riporta i dati aggiornati in OS (endpoint secondario) sebbene non vi sia la potenza statistica adeguata per un’analisi definitiva di questo endpoint. L’analisi di OS è stata prespecificata nel piano statistico al raggiungimento del 50% di eventi, ossia dopo 80 decessi.
Sono stati inoltre pubblicati i dati aggiornati relativi a ORR ad un follow up più maturo.
Ad un follow-up mediano di 13.6 mesi, gli eventi morte registrati nei tre bracci di trattamento sono stati 24 (braccio con sotorasib 960 mg-panitumumab), 28 (braccio con sotorasib 240 mg-panitumumab), e 30 (braccio di terapia standard).
Il vantaggio in OS non è risultato statisticamente significativo nei due bracci sperimentali, sebbene il trend fosse favorevole: HR 0.70 (95% CI, 0.41-1.18; P =0.20) con sotorasib 960 mg-panitumumab vs terapia standard e HR 0.83 (95% CI, 0.49-1.39; P= 0.50) con sotorasib 240 mg-panitumumab vs terapia standard.
Questo risultato potrebbe in parte essere correlato al crossover. L’esposizione a inibitori di KRAS era permessa dopo l’analisi primaria (PFS), ma non è stata effettuata “on protocol”. Quindici dei 33 pazienti assegnati al braccio standard e poi, successivamente, trattati con altri farmaci, hanno ricevuto un inibitore di KRAS G12C con EGFRi off-label o partecipando ad altre sperimentazioni.
L’ORR aggiornato è stato pari a 30.2% (95%CI, 18.3- 44.3) per sotorasib ad alta dose- panitumumab, 7.5% (95%CI, 2.1-18.2) per sotorasib a bassa dose- panitumumab e 2% per la terapia standard (95%CI, 0-9.9).
AEs correlati al trattamento di grado ≥3 nel 45.3%, 34.0% e 45.1% dei pazienti trattati rispettivamente con sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab e terapia a scelta dello sperimentatore; gli eventi avversi più comuni sono stati: dermatite acneiforme, ipomagnesemia ed eruzione cutanea con sotorasib 960 mg-panitumumab; ipomagnesemia e diarrea con sotorasib 240 mg-panitumumab; neutropenia, anemia e ipertensione con la terapia a scelta dello sperimentatore.
Nonostante il mancato raggiungimento del vantaggio in OS in ragione della non adeguata potenza statistica del trial relativamente a tale endpoint, i risultati positivi raggiunti in termini di PFS e tollerabilità sono a supporto del trattamento con sotorasib 960 mg-panitumumab come standard di cura nei pazienti con mCRC KRAS G12C chemiorefrattario, in un contesto relativamente povero di valide alternative terapeutiche.
A phase II study of monalizumab and durvalumab in patients with recurrent/metastatic squamous cell carcinoma of the head and neck: results of the I2 cohort of the EORTC-HNCG-1559 trial (UPSTREAM)
M + D has limited activity in advanced SCCHN pretreated with anti-PD(L)1.
Although the trial was negative, two patients presented with a response.
Investigating new drugs and translational research in advanced SCCHN is challenging. … (leggi tutto)
Il carcinoma a cellule squamose della testa e del collo (SCCHN) si presenta, nella maggior parte dei casi, come malattia localmente avanzata e, nonostante il trattamento multimodale con chirurgia e/o (chemio)radioterapia, più del 50% dei pazienti andrà incontro a ricaduta. Nei pazienti con SCCHN ricorrente/metastatico (R/M), la terapia di I linea con pembrolizumab in monoterapia se PD-L1 (CPS)≥1 o pembrolizumab associato a chemioterapia con platino, indipendentemente dai livelli di espressione di PD-L1, ha dimostrato un aumento in termini di OS. Ad oggi non esiste uno standard di cura per i pazienti che progrediscano dopo trattamento con platino e anti-PD-L1.
Lo studio UPSTREAM (EORTC-HNCG-1559), è un umbrella trial che ha arruolato oltre 400 pazienti con SCCHN R/M in progressione dopo terapia a base di platino. I pazienti sono stati assegnati a 5 coorti diverse sulla base di potenziali biomarcatori identificati in una nuova biopsia tumorale eseguita ai fini dello studio, con lo scopo di valutare l’efficacia di diverse terapie targeted. Pazienti già pretrattati con inibitori di PD-(L)1, non eleggibili per una delle 5 coorti per mancanza di un biomarker specifico, sono stati assegnati alla coorte I2, un sottostudio di fase II, randomizzato, non comparativo, in aperto e multicentrico, con lo scopo di valutare l’efficacia della combinazione immunoterapica durvalumab (PD-L1i) + monalizumab (NKG2Ai) rispetto alla terapia di controllo scelta dallo sperimentatore.
Sono stati arruolati 60 pazienti, randomizzati secondo rapporto 2:1: 42 pazienti hanno ricevuto la combinazione D + M e 18 pazienti sono stati trattati secondo la terapia prescritta dallo sperimentatore (metotrexato, paclitaxel, docetaxel, 5-fluorouracile, carboplatino, bleomicina, gemcitabina, mitomicina o migliore terapia di supporto). Il trattamento è stato proseguito fino a progressione di malattia o a tossicità inaccettabile.
L’endpoint primario era il tasso di risposta obiettiva (ORR) nelle prime 16 settimane di trattamento, definito come la percentuale di pazienti che avrebbero soddisfatto i criteri di risposta completa o parziale (PR) secondo RECIST 1.1. Nel braccio D + M, la migliore risposta osservata è stata una risposta parziale (PR) in un paziente [2.4%, (CI)95%= 0.1% – 12.6%]. Lo studio non ha pertanto raggiunto il suo endpoint primario. La migliore risposta è stata SD in 11 pazienti (26%, CI95% dal 12.9% al 39.5%), mentre c’è stata PD in 19 pazienti (45%, CI95% dal 29.9% al 61.3%). Nel braccio di controllo, sono state riportate 1 PR (5.6%, IC95% 0.1%-27.3%), 8 SD (44%, IC95% 21.5%-69-2%) e 6 PD (33%, IC95% 11.6%-55.1%). La durata mediana della stabilità di malattia è stata di 1.6 mesi (IC95%= 0.1-1.8 mesi) e 1.9 mesi (0.0-6.8 mesi), rispettivamente nel braccio D+M e nel braccio di controllo.
Per quanto riguarda gli endpoint secondari, la PFS mediana è stata di 2.0 mesi (IC95% 1.8-2.4 mesi) e 3.1 mesi (IC95% 1.9-3.9 mesi), rispettivamente nel braccio D + M vs braccio di controllo. La OS mediana è stata di 4.3 mesi (IC95% 3.3-8.9 mesi) e 8.0 mesi (IC95% 3.1-14.9 mesi), rispettivamente nel braccio D + M e nel braccio di controllo. Nel braccio D + M ci sono stati 7 decessi precoci per progressione di malattia alla prima rivalutazione.
TRAE di grado ≥3 (G3) sono stati segnalati in 4 (9%) pazienti nel braccio D + M (dispnea, polmonite, nefrite immuno-correlata e iperglicemia, ciascuna segnalata in 1 paziente) e nel 26% dei pazienti del braccio di controllo (anemia, neutropenia, sepsi, neuropatia periferica, mucosite).
La coorte I2 dello studio UPSTREAM non è riuscita a dimostrare l’efficacia della combinazione di D+M in una popolazione di pazienti con SCCHN ampiamente pretrattati e precedentemente esposti a terapia anti-PD(L)1. Nonostante l’esito negativo dello studio, due pazienti hanno mostrato una risposta di malattia: in particolare, un paziente ha ottenuto risposta completa di malattia per circa 3 anni. Ciò sottolinea l’importanza della ricerca traslazionale nell’identificazione di potenziali biomarcatori di risposta in contesti precoci, come, ad esempio, nel setting neoadiuvante.
In Europe
Nivolumab Plus Ipilimumab Shows a Significant OS Benefit Versus Lenvatinib or Sorafenib in Patients with Previously Untreated Unresectable HCC
May 20, 2025 – In an open-label, randomised, phase III CheckMate 9DW study, a combination of nivolumab plus ipilimumab showed a significant overall survival (OS) benefit over lenvatinib or sorafenib in patients with unresectable hepatocellular carcinoma (HCC) who had not received previous systemic treatment for advanced disease. This benefit was generally consistent across clinically relevant subgroups, including those based on disease aetiology … (leggi tutto)
huCART19-IL18 Shows Promising Efficacy at Low Cell Doses in Patients with Lymphoma After the Failure of Previous anti-CD19 CAR T-cell Therapy
May 19, 2025 – In a phase I study conducted at the University of Pennsylvania, the researchers found that autologous interleukin-18 (IL18) armoured chimeric antigen receptor (CAR) T cells had promising clinical activity in patients with relapsed or refractory CD19-positive lymphomas after the failure of previous anti-CD19 CAR T-cell therapy. The treatment was associated mainly with side effects of grade 1 or 2, with no unexpected or delayed effects observed … (leggi tutto)
ETF recommends updating COVID-19 vaccines to target new LP.8.1 variant
May 16, 2025 – EMA’s Emergency Task Force (ETF) has recommended updating COVID-19 vaccines to target the new SARS-CoV-2 variant LP.8.1 for the 2025/2026 vaccination campaign.
LP.8.1 differs from the JN.1 family targeted by previous updated vaccines and has now surpassed the JN.1 variant to become the most widely circulating variant worldwide.
In making its recommendation, the ETF consulted with the World Health Organization (WHO) … (leggi tutto)
FDA Approves Nivolumab with Ipilimumab for Unresectable or Metastatic Hepatocellular Carcinoma
May 16, 2025 – On 11 April 2025, the US Food and Drug Administration (FDA) approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). Efficacy was evaluated in CHECKMATE-9DW (NCT04039607), a randomised (1:1), open-label study … (leggi tutto)
EMA Recommends Extension of Therapeutic Indications for Nivolumab to Neoadjuvant and Adjuvant Treatment of NSCLC
May 15, 2025 – On 27 March 2025, 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 nivolumab (Opdivo).
The marketing authorisation holder for this medicinal product … (leggi tutto)
Interaction Between CMV Infection, Metastatic Melanoma Development, ICI Outcomes and Delayed Onset of irAEs
May 14, 2025 – Analysis of multiple cohorts of patients with melanoma for whom cytomegalovirus (CMV) serology could be determined in the Oxford Cancer Immunotherapy Toxicity and Efficacy (OxCITE) cohort study demonstrated a positive association between CMV serostatus and overall survival (OS) in patients treated with monotherapy, but not with a combination of immune checkpoint inhibitors (ICIs) … (leggi tutto)
Neoadjuvant PD1 Blockade Leads to Organ Preservation in a High Proportion of Patients with Early-Stage dMMR Solid Tumours Amenable to Curative-Intent Surgery
May 13, 2025 – Data from a phase II study, which were obtained from a small group of patients with stage I, II, or III mismatch repair-deficient (dMMR) solid tumours, show that neoadjuvant PD1 blockade enabled a non-operative management strategy in a high proportion of patients. As seen in the context of metastatic disease, the efficacy of immune checkpoint blockade appeared to be relatively tumour-agnostic, driven primarily by the dMMR phenotype rather than the … (leggi tutto)
Zongertinib Shows Clinical Benefit in Patients with Previously Treated HER2-mutated NSCLC
May 12, 2025 – A phase Ib study involving patients with previously treated HER2-mutated non-squamous advanced or metastatic non-small cell lung cancer (NSCLC) shows the antitumour activity of zongertinib at a dose of 120 mg. Responses with zongertinib were durable. Zongertinib had a manageable safety profile, and resulted in notably low levels of grade 3 or higher drug-related adverse events, including those associated with EGFR inhibitors … (leggi tutto)
FDA Approves Nivolumab with Ipilimumab for Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer
May 09, 2025 – On 8 April 2025, the US Food and Drug Administration (FDA) approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for adult and paediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single agent … (leggi tutto)
Dall’FDA
FDA ODAC Votes Against the Applicability of STARGLO Data for Glofitamab Plus Chemo for U.S. Patients With R/R DLBCL
May 20, 2025 – The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 1 against the applicability of the patient population and results from the phase 3 STARGLO trial (NCT04408638) to the United States (US) population of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) ... (leggi tutto)
FDA Awards RMAT Designation to BCB-276 CAR T-Cell Therapy for Diffuse Intrinsic Pontine Glioma
May 19, 2025 – TLX101 demonstrated a favorable safety profile and early clinical activity in recurrent high-grade glioma patients, with no serious adverse effects reported.
The median overall survival from TLX101 initiation was 12.4 months, supporting efficacy signals from previous studies ... (leggi tutto)
FDA Grants Fast Track Designation to DLL3-Targeted ADC ZL-1310 in ES-SCLC
May 19, 2025 – ZL-1310, a DLL3-targeted ADC, received FDA fast track designation for ES-SCLC, highlighting its potential as a novel therapeutic option.
Interim phase 1 trial data revealed a 74% overall response rate, with significant activity in patients with brain metastases.... (leggi tutto)
Five Under 5: Top Oncology Videos for the Week of 5/11
May 18, 2025 – Larotrectinib demonstrates durable, tumor-agnostic efficacy for NTRK fusion-positive tumors with a favorable toxicity profile, confirmed by pooled trial data. Mirvetuximab soravtansine shows promise for platinum-resistant ovarian cancer, with ongoing evaluation in the maintenance setting reflecting a shift toward personalized therapies. ... (leggi tutto)
The OncFive: Top Oncology Articles for the Week of 5/11
May 17, 2025 – Telisotuzumab vedotin received FDA approval for NSCLC with high c-MET overexpression, showing a 35% ORR in the LUMINOSITY trial.
Retifanlimab approved for advanced anal cancer, improving progression-free and overall survival in the POD1UM-303/InterAACT2 trial.
Belzutifan approved for pheochromocytoma and paraganglioma, with a 26% ORR and significant reduction in antihypertensive medication use ... (leggi tutto)
FDA Approves Retifanlimab for Advanced Anal Cancer
May 15, 2025 – Retifanlimab-dlwr (Zynyz) is approved with carboplatin and paclitaxel for first-line treatment of inoperable or metastatic SCAC.
Retifanlimab monotherapy is approved for SCAC patients with progression on or intolerance to platinum-based chemotherapy.
Approvals are based on phase 3 POD1UM-303/InterAACT2 and phase 2 POD1UM-202 trial results ... (leggi tutto)
FDA Green Lights Companion Diagnostic for Telisotuzumab Vedotin in NSCLC
May 15, 2025 – The VENTANA MET (SP44) RxDx Assay identifies NSCLC patients with high c-MET overexpression for telisotuzumab vedotin treatment.
The phase 2 LUMINOSITY trial showed a 35% overall response rate in patients with high c-MET expression treated with telisotuzumab vedotin.
Common adverse effects of telisotuzumab vedotin include peripheral neuropathy, fatigue, and decreased appetite, with some grade 3/4 laboratory abnormalities ... (leggi tutto)
FDA Approval of Penpulimab Expands Treatment Options in Recurrent/Metastatic Non-Keratinizing NPC
May 15, 2025 – The FDA approval of penpulimab-kcqx in combination with chemotherapy represents a significant advancement in the first-line treatment landscape for patients with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC), a rare malignancy with historically limited therapeutic options in the United States, according to Aditya Shreenivas, MD ... (leggi tutto)
FDA Grants Accelerated Approval to Telisotuzumab Vedotin In Pretreated Advanced NSCLC With c-MET Overexpression
May 14, 2025 – Telisotuzumab vedotin-tllv (Emrelis) received FDA accelerated approval for NSCLC with high c-MET protein overexpression after prior systemic therapy.
The phase 2 LUMINOSITY trial showed a 35% overall response rate and a median duration of response of 7.2 months for patients treated with telisotuzumab vedotin.
... (leggi tutto)
FDA Approves Belzutifan for Advanced Pheochromocytoma and Paraganglioma
May 14, 2025 – Belzutifan is approved for advanced pheochromocytoma or paraganglioma in patients 12 and older, based on LITESPARK-015 trial results.
The LITESPARK-015 trial showed a 26% overall response rate and a median duration of response of 20.4 months.
Belzutifan was previously approved for von Hippel-Lindau disease-associated tumors and advanced renal cell carcinoma. ... (leggi tutto)
Dall’ASCO
ASCO/ESMO Joint Session at ASCO25 Will Highlight Key Issues in Biomarker-Driven Therapeutics
May 15, 2025 – The ASCO/European Society for Medical Oncology (ESMO) Joint Session at the ASCO Annual Meeting will discuss international guidelines and perspectives on how to responsibly integrate molecular diagnostics into clinical care.
Experts will discuss how to leverage digital technologies to advance cancer research … (leggi tutto)
ctDNA Testing in CRC Management: Is It Ready for Primetime?
May 15, 2025 – An Education Session at the 2025 ASCO Annual Meeting will explore the role of circulating tumor DNA (ctDNA) testing in the management of colorectal cancer (CRC).
Emerging evidence suggests that liquid biopsy using ctDNA testing has the potential to guide treatment of CRC in the early-stage and metastatic settings.
Although many questions remain about the role of ctDNA testing, recent and ongoing trials should help elucidate its role in clinical practice … (leggi tutto)
Is Radiation Therapy Needed as Neoadjuvant Therapy for E/EGJ Tumors?
May 14, 2025 – For patients with resectable esophageal or esophagogastric junction (E/EGJ) adenocarcinoma, the current preferred standard of care is perioperative 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT).
For patients with squamous cell carcinoma (SCC), or those with adenocarcinoma considered not suitable for FLOT, the best evidence remains with trimodality therapy with neoadjuvant chemoradiation and surgery, followed by adjuvant immunotherapy if residual disease is present … (leggi tutto)
Electronic Patient-Reporting System Enables Remote Monitoring of Symptoms Following Major Urologic Cancer Surgery
May 14, 2025 – An electronic patient-reported symptom assessment tool delivered via a patient portal was found to be feasible and effective in patients discharged after major urologic cancer surgery.
Each day for the 10 days following surgery, patients received a message through a patient portal prompting them to complete a survey of symptoms, and the tool included an automated flagging system to alert clinicians if a patient reported a symptom requiring urgent attention … (leggi tutto)
Diagnostic and Therapeutic Advances Reshape Treatment Paradigms in Genitourinary Cancers
May 14, 2025 – An Education Session will take a deep dive into recent updates to standards of care and new drug approvals in the management of renal cell carcinoma (RCC) and urothelial carcinomas.
Faculty will address recent advances in imaging including new radiotracers, recent drug updates such as HIF2α inhibitor belzutifan for advanced RCC and the expanded use of antibody-drug conjugates (ADCs), and ongoing questions and challenges in the field … (leggi tutto)
Perioperative Therapy in Bladder Cancer: Moving Toward Personalization
May 14, 2025 – An Education Session will examine the evolving paradigm for the perioperative management of muscle-invasive bladder cancer (MIBC).
The session will explore the NIAGARA trial which led to the growing use of immunotherapy before and after surgery, regardless of pathologic response; however, the trial design left questions open regarding the relative contributions of preoperative and postoperative durvalumab to the improved outcomes … (leggi tutto)
Pillole dall’AIFA
20 maggio 2025 – Attivazione web e pubblicazione schede di monitoraggio – Registro ELREFXIO
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16 maggio 2025 – Attivazione web e pubblicazione schede di monitoraggio – Registro ALECENSA ADIUVANTE (NSCLC)
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16 maggio 2025 – Ordine del giorno riunione Commissione Scientifica e Economica del Farmaco (CSE)
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16 maggio 2025 – Aggiornamento “Diario di bordo sulla Trasparenza”
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16 maggio 2025 – Eugenia Cogliandro eletta presidente della Commissione della Farmacopea europea
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15 maggio 2025 – AIFA aggiorna le Liste di Trasparenza
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14 maggio 2025 – Il CdA AIFA approva la rimborsabilità di 11 farmaci
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