Oggi in Oncologia
Biomarker Data from the Phase III KATHERINE Study of Adjuvant T-DM1 versus Trastuzumab for Residual Invasive Disease after Neoadjuvant Therapy for HER2-Positive Breast Cancer
Purpose: In KATHERINE, adjuvant T-DM1 reduced risk of disease recurrence or death by 50% compared with trastuzumab in patients with residual invasive breast cancer after neoadjuvant therapy (NAT) comprised of HER2-targeted therapy and chemotherapy. This analysis aimed to identify biomarkers of response and differences in biomarker expression before and after NAT … (leggi tutto)
Nello studio di Denkert et Al si sono confrontati i dati di sopravvivenza libera da malattia (IDFS), in relazione a vari biomarcatori, nel contesto dello studio di fase III KATHERINE, che ha confrontato trastuzumab emtansine (T-DM1) versus trastuzumab in pazienti con residuo di malattia dopo terapia neoadiuvante per tumore della mammella HER2+ (cT1–4, N0–3,M0 esclusi T1aN0 e T1bN0). Lo studio ha riportato la netta superiorità del T-DM1 in termini di IDFS.
L’analisi dei biomarcatori si è focalizzata sulla proteina HER2, la sua amplificazione ed espressione genica, lo stato della mutazione PIK3CA, l’espressione del gene PD-L1, del gene CD8, insieme a diverse signatures geniche immunitarie inerenti le cellule T-effettrici, valutandone il loro potenziale valore prognostico e predittivo.
Le metodiche utilizzate per l’analisi di questi biomarcatori hanno compreso il sequenziamento del DNA e dell’RNA, analisi dell’intero trascrittoma cellulare e immunoistochimica (IHC). Tramite IHC e ibridazione in situ sono state analizzate le differenze nell’espressione genica tra i tessuti pre- e post-terapia neoadiuvante (NAT) e loro potenziali implicazioni.
Il beneficio del trattamento con T-DM1 è risultato indipendente dai livelli di espressione di HER2, con una percentuale di IDFS a 3 anni dell’89% nel sottogruppo IHC 3+ e dell’85% nel sottogruppo IHC 2+. Il vantaggio con T-DM1 è stato osservato sia nei tumori con espressione HER2 omogenea (≥80%) che eterogenea (30%–79%). La maggiore efficacia del trattamento con T-DM1, tuttavia, non è stata osservata nei tumori con espressione focale di HER2 (<30%) a testimonianza di una minore espressione di HER2 e una maggiore eterogeneità biologica pre-NAT.
I benefici superiori del T-DM1 sono stati confermati nelle pazienti con e senza mutazione di PIK3CA (HR 0.54 e di 0.48, rispettivamente), risultato che non conferisce al gene PIK3CA un ruolo predittivo, ma neanche prognostico negativo.
Riguardo le differenze di espressione degli mRNA di HER2, non si è riscontrata un’influenza significativa sulla IDFS garantita dal T-DM1, benché l’analisi approfondita mediante sequenziamento dell’RNA si sia potuta eseguire per un numero congruo di campioni soltanto post-NAT. Discorso analogo per i livelli di espressione degli mRNA relativi ad altri biomarcatori, quali PD-L1, CD8 e le signatures immunologiche valutate post-NAT. Per quest’ultime, tuttavia, sono state registrate differenze evidenti nei confronti dei campioni disponibili pre-NAT, con una maggiore attivazione del microambiente immunitario successiva alla NAT.
Un’elevata espressione del gene HER2 è stata associata ad incremento del rischio di recidiva o morte nel braccio di trattamento con trastuzumab, ma non con T-DM1, coerentemente con la capacità di T-DM1 di superare la resistenza a HER2.
L’analisi di Denkert et al. fornisce i primi risultati completi sulla relazione tra l’espressione dei biomarcatori e la ricaduta di malattia nel tumore residuo dopo terapia target HER2+.
La natura esplorativa delle analisi dei biomarcatori si dimostra fondamentale per una migliore comprensione dell’evoluzione clinica della patologia in relazione ai trattamenti, con potenziale grande impatto sulla ricerca dei fattori predittivi di risposta alle terapie oncologiche.
In Europa
Adding Pembrolizumab to Chemotherapy with or without Bevacizumab Improves Overall Survival Across Subgroups of Patients with Persistent, Recurrent, or Metastatic Cervical Cancer
Jan 09, 2024 – In KEYNOTE-826 study conducted in 617 patients with cervical cancer, subgroup analyses indicate the benefit of adding pembrolizumab to chemotherapy with or without bevacizumab was generally sustained across a broad selection of patient subgroups defined by bevacizumab use, platinum use, prior chemoradiotherapy (CRT) exposure, and histologic type ... (leggi tutto)
Mosunetuzumab Plus Polatuzumab Vedotin Shows Promise for Patients with Aggressive Relapsed or Refractory Aggressive Large B Cell Lymphoma
Dec 21, 2023 – A phase Ib/II study demonstrated that mosunetuzumab with polatuzumab vedotin, a combination regimen targeting two biologically relevant B cell targets using a T-cell-engaging bispecific antibody and an antibody–drug conjugate, induced durable responses in patients with relapsed or refractory large B cell lymphoma, including patients with poor clinical and pathologic prognostic features, such as relapse after CAR-T cell therapy ... (leggi tutto)
Oligoprogression in Metastatic NSCLC Could Be Effectively Treated with SBRT Plus Standard-of-Care, Leading to Increase in PFS Compared with Standard-of-Care Only
Dec 21, 2023 – The results of first phase II, open-label, randomised controlled study of stereotactic body radiotherapy (SBRT) targeting oligoprogressive sites in patients with metastatic breast cancer or non-small cell lung cancer (NSCLC) after having received at least first-line systemic therapy, with oligoprogression defined as 5 or less progressive lesions on PET/CT or CT show increase in progression-free survival (PFS) in the SBRT plus standard-of-care … (leggi tutto)
Divarasib in Combination with Cetuximab Demonstrates a Manageable Safety Profile and Promising Activity in Patients with KRAS G12C-positive CRC
Dec 20, 2023 – The KRAS G12C mutation is associated with worse overall survival in patients with colorectal cancer (CRC). Current first-line standard of care for KRAS G12C-positive advanced CRC includes 5-FU-based chemotherapy with irinotecan, oxaliplatin and/or capecitabine, but is limited by low tumour-specific selectivity and systemic toxicity. Several KRAS G12C inhibitors, including sotorasib, adagrasib, and divarasib are currently being investigated as a single agent … (leggi tutto)
Midterm report on 2025 network strategy highlights good progress during critical period of the pandemic
Dec 20, 2023 – The European medicines regulatory network is on track to meet its strategic goals and objectives covering availability and accessibility of medicines; data analytics, digital tools, and digital transformation; innovation; antimicrobial resistance and other emerging health threats; supply-chain challenges; sustainability of the network and operational excellence, according to the midterm report of the network strategy ... (leggi tutto)
Dall’FDA
FDA Grants Priority Review to Tisotumab Vedotin sBLA for Recurrent or Metastatic Cervical Cancer
Jan 09, 2024 – The FDA has granted priority review to a supplemental biologics license application (sBLA) seeking to convert the accelerated approval of tisotumab vedotin-tftv (Tivdak) to a full approval for the treatment of patients with recurrent or metastatic cervical cancer whose disease progresses on or following frontline therapy. … (leggi tutto)
FDA Issues CRL to Zolbetuximab for Advanced HER2–, CLDN18.2+ Gastric/GEJ Cancer
Jan 09, 2024 – The FDA has issued a complete response letter (CRL) regarding the biologics license application (BLA) seeking the approval of zolbetuximab for the treatment of patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are Claudin18.2 (CLDN18.2) positive … (leggi tutto)
FDA Grants Fast Track Status to Rinatabart Sesutecan for FRα-Expressing Ovarian Cancer
Jan 08, 2024 – The FDA has granted fast track designation to the novel folate receptor alpha (FRα)–targeted antibody-drug conjugate (ADC) rinatabart sesutecan (Rina-S; PRO1184) for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer. Rina-S consists of an FRα-directed antibody linked to sesutecan, a novel, cleavable hydrophilic linker developed by ProfoundBio … (leggi tutto)
FDA Roundup: January 5, 2024
Jan 05, 2024 – Today, the U.S. Food and Drug Administration is providing an at-a-glance summary of news from around the agency: On Wednesday, the FDA issued a safety communication to inform health care providers not to use the Total Hip System, including resurfacing implants, manufactured by Synovo Production, Inc. (Synovo) and to inform patients who may … (leggi tutto)
FDA Grants Breakthrough Therapy Designation to TAR-200 for BCG-Unresponsive High-Risk NMIBC
Jan 05, 2024 – The FDA has granted breakthrough therapy designation to TAR-200 for use in the treatment of patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-risk non–muscle invasive bladder cancer who are not candidates for or opted not to receive radical cystectomy. The designation is supported by findings from the phase 2b SunRISe-1 trial (NCT04640623) in which TAR-200 elicited durable responses in this population. … (leggi tutto)
BLA Submitted to FDA for PET Imaging Agent TLX250-CDx in RCC
Jan 04, 2024 – A biologics license application (BLA) seeking the approval of the investigational positron emission tomography (PET) imaging agent 89Zr-DFO-girentuximab (TLX250-CDx; Zircaix) in clear cell renal cell carcinoma (ccRCC) has been submitted to the FDA. The submission is based on data from the global phase 3 ZIRCON trial (NCT03849118) in which the investigational imaging agent proved more effective than traditional PET/CT … (leggi tutto)
FDA Grants Fast Track, Breakthrough Therapy Designations to Cretostimogene Grenadenorepvec for NMIBC
Jan 03, 2024 – The FDA has granted fast track and breakthrough therapy designations to cretostimogene grenadenorepvec (CG0070) for use as a potential therapeutic option in patients with high-risk Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without Ta or T1 tumors.The decision is supported by findings from ongoing clinical trials, including the phase 3 BOND-003 trial (NCT04452591) … (leggi tutto)
FDA Issues Complete Response Letter to Sotorasib for KRAS G12C–Mutated NSCLC
Jan 02, 2024 – The FDA has issued a complete response letter (CRL) to the supplemental new drug application seeking the full approval of sotorasib (Lumakras) for patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC).1 The FDA also issued a new postmarketing requirement (PMR) for an additional confirmatory trial to support full approval of sotorasib for this patient population. This trial will be completed by February 2028 at the latest … (leggi tutto)
FDA Approves Kidney Cancer Therapy After Dana-Farber-Led Research Shows Improved Outcomes for Patients with Advanced Disease
Dec 31, 2023 – Belzutifan, a HIF-2α inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with advanced kidney cancer previously treated with immune checkpoint inhibitors and anti-angiogenic therapies. The FDA approval was based on the results of the phase 3 LITESPARK-005 trial, a study led by Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Cancer at Dana-Farber Cancer Institute … (leggi tutto)
OncLive December Recap: FDA Approval Highlights
Dec 30, 2023 – In case you missed it, below are some of the drugs that were approved by the FDA in the month of December: Enfortumab Vedotin Combo Snags Approval in Urothelial Cancer Most recently, on December 15, 2023, the FDA granted full approval to enfortumab vedotin-ejfv (Padcev) paired with pembrolizumab (Keytruda) … (leggi tutto)
FDA Approves Delivery System of Biosimiliar Pegfilgrastim-cbqv for Febrile Neutropenia
Dec 26, 2023 – The FDA has approved an on-body injector (OBI) presentation of the biosimilar pegfilgrastim-cbqv biosimilar (Udencya), known as Udencya Onbody, which is administered to patients with cancer the day after chemotherapy in order to decrease infection incidence from febrile neutropenia. The FDA has approved an on-body injector (OBI) presentation of the biosimilar pegfilgrastim-cbqv biosimilar (Udencya) … (leggi tutto)
Capivasertib/Fulvestrant Approval Expands Options in PIK3CA/AKT1/PTEN-Altered HR+/HER2– Breast Cancer
Dec 22, 2023 – Capivasertib (Truqap) plus fulvestrant (Faslodex) provides another effective and safe treatment option for patients with hormone receptor (HR)–positive, HER2-negative, locally advanced or metastatic breast cancer after CDK4/6 inhibition. However, genomic information and a deeper understanding of toxicity management are necessary to navigate this expanding armamentarium, according to Sara M. Tolaney, MD, MPH … (leggi tutto)
Patritumab Deruxtecan BLA Receives Priority Review in NSCLC
Dec 22, 2023 – The FDA has accepted and granted priority review to the biologics license application (BLA) seeking the approval of the HER3-directed antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who previously received at least 2 systemic therapies … (leggi tutto)
FDA Approves Label Updates to Include New Data for Axi-Cel in LBCL, Zanubrutinib in CLL
Dec 22, 2023 – The FDA has approved label updates for zanubrutinib (Brukinsa) to include positive progression-free survival (PFS) data from the phase 3 ALPINE trial (NCT03734016) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), and axicabtagene ciloleucel (axi-cel; Yescarta) to include findings from the primary overall survival (OS) analysis of the phase 3 ZUMA-7 trial (NCT03391466) in patients with relapsed/refractory large B-cell lymphoma (LBCL) … (leggi tutto)
FDA Grants Breakthrough Therapy Designation to BNT323/DB-1303 in Endometrial Cancer
Dec 21, 2023 – The FDA has granted breakthrough therapy designation to the HER2-targeted antibody-drug conjugate (ADC) BNT323/DB-1303 for use as a potential therapeutic option in patients with advanced endometrial cancer who have progressed on or after treatment with immune checkpoint inhibitors. This decision was supported by topline data from a phase 1/2 trial (NCT05150691), in which BNT323/DB-1303 elicited an unconfirmed overall … (leggi tutto)
sBLA and NDA Submitted to FDA for Amivantamab and Lazertinib in EGFR-Mutant NSCLC
Dec 21, 2023 – A supplemental biologics license application and new drug application seeking the approval of amivantamab-vmjw (Rybrevant) plus lazertinib as frontline therapy for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test, have been submitted to the FDA … (leggi tutto)
Dall’ASCO
ASCO and SSO Publish New Guideline on Germline Testing in Breast Cancer
Jan 05, 2024 – ASCO in partnership with the Society of Surgical Oncology (SSO) has released a new guideline addressing recommendations in germline testing in patients with breast cancer. The guideline provides oncologists with a framework for how to approach germline testing and recommendations for who should be tested and what genes should be tested to support risk assessment and treatment decision-making. … (leggi tutto)
Personalizing Adjuvant Treatment Using ctDNA in Colon Cancer
Jan 04, 2024 – Circulating tumor DNA (ctDNA) is considered to be a surrogate marker for minimal residual disease (MRD) and a predictive marker to determine the risk of colon cancer recurrence. Patients with colon cancer with detectable ctDNA post–curative-intent therapy (MRD-positive) are at a remarkable risk of recurrence (95% to 100%) if not offered systemic therapy, which suggests that MRD positivity is not just a high-risk marker for recurrence but also a measure of persistent … (leggi tutto)
Selecting Patients for Frontline CDK4/6 Inhibitors in Metastatic Breast Cancer
Jan 04, 2024 – The current standard of care in the United States for first-line metastatic hormone-sensitive breast cancer remains adding a CDK4 inhibitor to endocrine therapy treatment in most patients, given the survival benefit noted with ribociclib and abemaciclib. The SONIA trial showed that endocrine therapy alone should be considered as first-line treatment in patients with hormone-sensitive de novo metastatic breast cancer … (leggi tutto)
Is Pathologic Complete Response the Best Surrogate Endpoint for Survival in Esophagogastric Cancer?
Jan 03, 2024 – The gold standard for definitive treatment of patients with locally advanced esophagogastric adenocarcinoma (EGA) is perioperative FLOT, but the cure rate is only 50%; thus, new therapeutic strategies are required. Pathologic complete response (pCR) is a measure of neoadjuvant treatment efficacy that has been associated with prolonged survival in chemotherapy trials … (leggi tutto)
Emerging Biomarkers: Optimizing Melanoma Management in the Immunotherapy Era
Dec 21, 2023 – Melanoma biomarkers currently under investigation include diagnostic biomarkers such as circulating tumor DNA (ctDNA); prognostic biomarkers such as gene expression profiling (GEP); and predictive biomarkers including immune checkpoint expression and tumor mutational burden (TMB). Of emerging biomarker technologies, longitudinal monitoring of ctDNA appears most likely to enter routine use in the near future … (leggi tutto)
Pillole dall’AIFA
08 gennaio 2024 – Tabelle farmaci di classe A e H al 17/07/2023
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08 gennaio 2024 – Modifica Registri Veklury (remdesivir)
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08 gennaio 2024 – Notifica dei provvedimenti – Ufficio Ispezioni e Autorizzazioni GMP Medicinali
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05 gennaio 2024 – Aggiornamento “Diario di bordo sulla Trasparenza”
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05 gennaio 2024 – Ordine del giorno Riunione Commissione Tecnico Scientifica (CTS)
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02 gennaio 2024 – Modifica Registri Spinraza ed Evrysdi
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29 dicembre 2023 – Aggiornamento “Diario di bordo sulla Trasparenza”
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29 dicembre 2023 – Valutazione dell’impatto ambientale dei farmaci: incontro di esperti europei in AIFA
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29 dicembre 2023 – Farmaci biosimilari in Italia: report AIFA aggiornati ad agosto 2023
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29 dicembre 2023 – Ispettorato GCP – Utilizzo dei sistemi elettronici nell’ambito delle sperimentazioni cliniche dei medicinali
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22 dicembre 2023 – Aggiornamento “Diario di bordo sulla Trasparenza”
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22 dicembre 2023 – Esiti della riunione del Comitato Prezzi e Rimborso (CPR)
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22 dicembre 2023 – Monitoraggio della spesa farmaceutica (gennaio – agosto 2023)
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22 dicembre 2023 – Aggiornamento scheda Multifarmaco di monitoraggio semplificato intravitreali anti VEGF – XIMLUCI
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21 dicembre 2023 – Banidi AIFA 2023: avviso per la nomina dei componenti delle commissioni di valutazione dei protocolli di studio
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21 dicembre 2023 – Import/export del sangue e dei suoi prodotti: AIFA aggiorna istruzioni operative e modulistica
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21 dicembre 2023 – Aggiornamento procedura operativa Fondo 5% AIFA
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21 dicembre 2023 – Attivazione web e pubblicazione schede di monitoraggio – Registro ENHERTU (ca. mammario HER2-low)
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21 dicembre 2023 – Attivazione web e pubblicazione schede di monitoraggio – Registro ENHERTU (GEJ)
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21 dicembre 2023 – Attivazione web e pubblicazione schede di monitoraggio – Registro POLIVY
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21 dicembre 2023 – Chiusura del Registro di monitoraggio antivirali orali COVID-19
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21 dicembre 2023 – Attivazione web e pubblicazione schede di monitoraggio – Registro PAXLOVID
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20 dicembre 2023 – Nota Informativa Importante su Leqvio
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20 dicembre 2023 – Notifica dei provvedimenti – Ufficio Ispezioni e Autorizzazioni GMP Medicinali
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20 dicembre 2023 – AIFA e Polo Strategico Nazionale: un passo importante verso il futuro digitale del Paese
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