Comitato scientifico editoriale: Giuseppe Aprile, Consuelo Buttigliero, Paolo Carlini, Maria Vittoria Dieci, Massimo Di Maio, Raffaele Giusti, Domenica Lorusso, Cristina Masini, Laura Noto, Silvia Novello, Giuseppe Procopio, Daniele Santini Editore: Intermedia – Direttore Responsabile: Mauro Boldrini
Oggi in Oncologia
Pembrolizumab After Completion of Locally Ablative Therapy for Oligometastatic Non–Small Cell Lung Cancer A Phase 2 Trial
Patients with oligometastatic non–small cell lung cancer (NSCLC) may benefit from locally ablative therapy (LAT) such as surgery or stereotactic radiotherapy. Prior studies were conducted before the advent of immunotherapy, and a strong biological rationale for the use of immunotherapy exists in a minimal residual disease state. To evaluate whether the addition of pembrolizumab after LAT improves outcomes for patients with oligometastatic NSCLC … (leggi tutto)
Si tratta di uno studio monocentrico di fase II in cui la somministrazione di pembrolizumab dopo trattamento ablativo (terapia locale) si associa ad un vantaggio in outcomes in pazienti con NSCLC oligometastatico. Vengono valutati 45 casi con 4 o meno siti metastatici trattati da febbraio 2015 a settembre 2017 presso l’Abramson Cancer Center con pembrolizumab 200 mg ogni 21 gg per un totale di 8 cicli. Il trattamento poteva proseguire fino ad un totale di 16 cicli (in assenza di progressione e/o effetti collaterali di rilievo). La terapia con pembrolizumab iniziava fra la quarta e la dodicesima settimana dopo la fine della terapia ablativa su tutti i siti di malattia. L’obiettivo primario era la sopravvivenza libera da progressione (PFS) dall’inizio della terapia ablativa e la PFS dall’inizio della terapia con pembrolizumab. Lo studio è stato calibrato per un confronto storico con la PFS dall’inizio della terapia locale. Era prevista anche una valutazione della qualità di vita (QoL) mediante Functional Assessment of Cancer Therapy-Lung (FACT-L). Dopo un follow-up mediano di 23,2 mesi nei pazienti sopravvissuti, la PFS mediana dall’inizio della terapia era pari a 19,1 mesi (significativamente superiore ad uno storico 6,6 mesi; p = 0,005). La PFS mediana dall’inizio di pembrolizumab risultava pari a 18,7 mesi. Il 40% dei pazienti ha eseguito 16 cicli con una sopravvivenza globale (OS) stimata a 12 mesi del 90,2% e 77,5% a 24 mesi. Non venivano evidenziate correlazioni fra il dato di PFS e l’espressione di PD-L1 o infiltrato cellulare. Tra gli effetti collaterali (ogni grado) correlati a pembrolizumab i più frequenti sono stati: dolore (42%), fatigue (36%) e rash (22%). I più frequenti di grado 3 o 4: polmonite (6%), essendo le polmoniti di ogni grado presenti in 5 pazienti (11%); coliti di grado 3 in 2 pazienti e due pazienti con insufficienza surrenalica (una di grado 2 e una di grado 3). Nessun cambiamento significativo in termini di QoL fra il basale e il ciclo 8 né fra ciclo 8 e 16. Pur con le sue limitazioni, questo studio dà indicazioni rilevanti, soprattutto in un contesto in cui spesso si agisce al di fuori e/o in assenza di precise linee guida.
ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer
Enzalutamide, a potent androgen-receptor inhibitor, has demonstratedsignificant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide inmetastatic hormone-sensitive prostate cancer (mHSPC). ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, where in 1,150 men with mHSPC wererandomly assigned 1:1 to enzalutamide (160 mg/day) or … (leggi tutto)
Nello studio di fase III ARCHES, 1.150 pazienti affetti da carcinoma della prostata metastatico ormonosensibile sono stati randomizzati a ricevere enzalutamide versus placebo in associazione a terapia di deprivazione androgenica con l’obiettivo di definire l’efficacia di enzalutamide in fase di ormonosensibilità in termini di sopravvivenza libera da progressione radiologica. I pazienti sono stati stratificati per precedente trattamento con docetaxel e per carico di malattia (high vs low volume secondo i criteri stabiliti dallo studio Charteed). Lo studio ha raggiunto l’endpoint primario dimostrando come l’associazione di enzalutamide e terapia di deprivazione androgenica riduca il rischio di progressione radiologica o morte del 61% rispetto alla sola terapia di deprivazione androgenica (n = 1.150; HR = 0,39 [IC 95%: 0,30-0,50]; p < 0,0001). Tale vantaggio si è mantenuto indipendentemente dalla precedente esposizione a docetaxel e dal volume di malattia (high vs low). Il trattamento con enzalutamide nella malattia ormonosensibile ha determinato inoltre un vantaggio in termini di progressione sierologica, di tempo all’inizio di una linea terapeutica, tempo alla comparsa del primo evento scheletrico, tempo alla comparsa di resistenza alla castrazione e di progressione clinica (comparsa di dolore). Il tasso di pazienti che ha ottenuto un azzeramento del PSA ed una risposta obiettiva radiologica è stato superiore nel braccio di trattamento con enzalutamide (p < 0,001). Eventi avversi di grado 3 o superiore sono stati riportati nel 24,3% dei pazienti trattati con enzalutamide in associazione a terapia di deprivazione androgenica rispetto al 25,6% di quelli trattati con sola terapia di deprivazione androgenica. Lo studio ARCHES pertanto ha dimostrato l’efficacia di enzalutamide nel ritardare la progressione di malattia nel carcinoma prostatico metastatico ormonosensibile, andando ad arricchire il bagaglio terapeutico in questo setting di malattia. La peculiarità di questo studio rispetto agli studi analoghi con docetaxel ed abiraterone risiede nell’aver incluso pazienti trattati con chemioterapia ed averne dimostrato l’efficacia indipendentemente dal volume di malattia.
The association between metformin and ovarian cancer survival: a systematic review and meta-analysis of cohort studies
A number of observational studies examined the association between metformin therapy and ovarian cancer survival outcomes, but the results are inconsistent. To investigate the effect of metformin on survival for ovarian cancer patients. PubMed, Embase and Web of Science databases were searched for relevant studies from the inception to June11, 2019. The strength of the relationship was assessed using summary hazard ratios (HRs) with corresponding 95% confidence intervals … (leggi tutto)
Questa metanalisi, condotta su 6 studi retrospettivi e 2.638 pazienti con tumore ovarico che hanno associato in vario modo e con varie schedule la metformina, ipoglicemizzante orale con proprietà antitumorali descritte in altri tumori, alla chemioterapia non ha dimostrato alcun effetto benefico della metformina nelle pazienti con tumore ovarico né in termini di sopravvivenza libera da progressione (HR 0,49; p = 0,0106), né in termini di sopravvivenza globale (HR 0,78; p = 0,175). Questi dati, ancorché preliminari e con un livello di evidenza basso/moderato perché proveniente da metanalisi di studi retrospettivi, non sembrano dimostrare un beneficio della metformina nel carcinoma ovarico. Sono in corso studi prospettici e randomizzati che risponderanno con un livello di evidenza 1 al quesito.
In Europa
EMA/FDA analysis shows high degree of alignment in marketing application decisions between EU and US
Aug 16, 2019 – EMA and the US Food and Drug Administration (FDA) are aligned in more than 90% of marketing authorisation decisions for new medicines. This is one of the findings of a joint EMA/FDA analysis comparing decisions on 107 new medicine applications at the two agencies between 2014 and 2016. The study also looked at applications for which the agencies had differing outcomes in terms of type of approval and indication. The most common reason for … (leggi tutto)
Ibrutinib EU Indications Expanded in CLL and Waldenstrom Macroglobulinemia
Aug 13, 2019 – The European Commission has expanded the approval of ibrutinib to include use in combination with obinutuzumab for adult patients with previously untreated chronic lymphocytic leukemia (CLL), and also in combination with rituximab for the treatment of adult patients with Waldenström macroglobulinemia (WM). The expanded indications stem from a positive recommendation from the European Medicines Agency’s Committee for Medicinal … (leggi tutto)
NICE Approves Frontline Pembrolizumab Regimen for Squamous NSCLC
Aug 8, 2019 – The UK’s National Institute for Health and Care Excellence has authorized the use of pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel for the treatment of patients with metastatic squamous non–small cell lung cancer (NSCLC). The pembrolizumab combination is now available through the Cancer Drugs Fund to National Health Service patients in England. “The committee heard from the patient experts that … (leggi tutto)
Supporting medicine developers in generating quality data packages in early access approaches (PRIME and breakthrough therapies): workshop report published
July 31, 2019 – EMA and the US Food and Drug Administration (FDA) have published today a report on their joint workshop with stakeholders held on 26 November 2018. The aim of this workshop was to discuss scientific and regulatory approaches to address quality and manufacturing challenges encountered during the development of medicines under early access programmes, such as the PRIority MEdicines scheme (PRIME) in the European Union and the … (leggi tutto)
Names of liposomal medicines to be changed to avoid medication errors
July 31, 2019 – All marketing authorisation holders of medicines containing liposomal drug delivery systems are requested to submit to EU regulators a variation to change the names of these medicines as soon as possible before the end of September 2019. This recommendation was made jointly by EMA’s human medicines committee (CHMP) and the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) at their July meetings … (leggi tutto)
Frontline Atezolizumab Plus Carboplatin/Nab-Paclitaxel Nears EU Approval in Nonsquamous NSCLC
July 29, 2019 – The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has granted a positive opinion to the triplet regimen of atezolizumab, carboplatin, and nab-paclitaxel for the first-line treatment of patients with advanced, nonsquamous non–small cell lung cancer (NSCLC) who do not have EGFR or ALK molecular aberrations. The recommendation is based on interim data from the phase III IMpower130 study, which showed that the … (leggi tutto)
EU Panel Backs Pembrolizumab Plus Axitinib for Frontline RCC
July 29, 2019 – The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of pembrolizumab in combination with axitinib for the frontline treatment of patients with advanced renal cell carcinoma (RCC). The CHMP based its positive opinion on findings from the phase III KEYNOTE-426 trial, which demonstrated that frontline pembrolizumab/axitinib led to a 47% (HR, 0.53; 95% CI, 0.38-0.74; P <.0001) reduction … (leggi tutto)
Atezolizumab Plus Chemo Poised for EU Approval in Small Cell Lung Cancer
July 29, 2019 – The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of atezolizumab in combination with carboplatin and etoposide for the frontline treatment of patients with extensive-stage small cell lung cancer (SCLC). The positive opinion is based on findings from the phase III IMpower133 trial, in which the combination regimen significantly improved progression-free and overall survival (OS) compared with … (leggi tutto)
Elotuzumab Triplet Approaches EU Approval for Multiple Myeloma
July 29, 2019 – The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approving elotuzumab for use in combination with pomalidomide and low-dose dexamethasone (EPd) for the treatment of patients with relapsed/refractory multiple myeloma following 2 or more prior therapies, including lenalidomide and a proteasome inhibitor (PI). The CHMP based its positive opinion on findings from the phase II ELOQUENT-3 … (leggi tutto)
Dall’FDA
FDA Grants Zanubrutinib Priority Review for Relapsed/Refractory Mantle Cell Lymphoma
Aug 21, 2019 – The FDA has granted a priority review designation to a new drug application (NDA) for zanubrutinib (BGB-3111) for the treatment of patients with mantle cell lymphoma (MCL) who have received ≥1 prior therapy. The application is based on data from an international phase I/II trial (NCT02343120) in patients with B-cell lymphomas, a group of patients with relapsed/refractory MCL in China in a phase II trial (NCT03206970), pooled safety data from 5 clinical … (leggi tutto)
FDA Grants Enzalutamide Priority Review for Metastatic Hormone-Sensitive Prostate Cancer
Aug 21, 2019 – The FDA has granted a priority review designation to a supplemental new drug application for enzalutamide for the treatment of men with metastatic hormone-sensitive prostate cancer (mHSPC), according to Astellas Pharma Inc. and Pfizer Inc., the codevelopers of the androgen receptor inhibitor. The designation, which will expedite the development and review of enzalutamide in this setting, is based on data from the phase III ARCHES and ENZAMET … (leggi tutto)
Statement on new results demonstrating continued success of the agency’s youth smoking prevention efforts and significant public health cost savings
Aug 20, 2019 – As someone who has dedicated his life to reducing the public health burden and suffering caused by cancer, it is all too clear that we must do everything we can to prevent kids from starting down a path of a lifelong addiction to tobacco and its associated harms. At the U.S. Food and Drug Administration, a critical component of our work to protect kids and significantly reduce tobacco-related disease and death has been to deploy highly successful … (leggi tutto)
FDA OCE and Syapse Announce Research Collaboration Focused on Regulatory Use of Real-World Evidence
Aug 19, 2019 – Syapse and the U.S. Food and Drug Administration (FDA) Oncology Center of Excellence (OCE) have signed a multiyear research collaboration agreement focused on the use of real-world evidence to support regulatory decision-making. Syapse and the OCE will work with stakeholders across the FDA to address key regulatory questions about testing and treatment patterns, dosing and safety, and outcomes in oncology with a focus on precision … (leggi tutto)
FDA Approves Fedratinib for Myelofibrosis
Aug 16, 2019 – The FDA has approved fedratinib for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis. The approval is based on findings from the phase III JAKARTA2 study, which evaluated fedratinib in patients with primary or secondary myelofibrosis; results demonstrated a significant reduction in splenomegaly and symptom burden in patients … (leggi tutto)
FDA Review Finds No Increased Risk of Prostate Cancer With Parkinson’s Disease Treatments Containing Entacapone
Aug 15, 2019 – A U.S. Food and Drug Administration (FDA) review of additional data found no increased risk of prostate cancer with the use of entacapone to treat Parkinson’s disease. The FDA conducted this review after an earlier trial – the Stalevo Reduction in Dyskinesia Evaluation–Parkinson’s Disease (STRIDE-PD) trial – suggested this possible risk. As a result, the FDA’s recommendations for using entacapone and the combination of entacapone, carbidopa … (leggi tutto)
FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor
Aug 15, 2019 – The U.S. Food and Drug Administration today granted accelerated approval to entrectinib, a treatment for adult and adolescent patients whose cancers have the specific genetic defect, NTRK (neurotrophic tyrosine receptor kinase) gene fusion and for whom there are no effective treatments. “We are in an exciting era of innovation in cancer treatment as we continue to see development in tissue agnostic therapies, which have the potential to transform cancer … (leggi tutto)
FDA proposes new required health warnings with color images for cigarette packages and advertisements to promote greater public understanding of negative health consequences of smoking
Aug 15, 2019 – Today, the U.S. Food and Drug Administration issued a proposed rule to require new health warnings on cigarette packages and in advertisements to promote greater public understanding of the negative health consequences of smoking. The proposed warnings, which feature photo-realistic color images depicting some of the lesser-known, but serious health risks of cigarette smoking, stand to represent the most significant change to cigarette labels in more than … (leggi tutto)
FDA Grants Acalabrutinib Breakthrough Designation for CLL
Aug 14, 2019 – The FDA has granted a breakthrough therapy designation to acalabrutinib for the treatment of patients with chronic lymphocytic leukemia (CLL). The designation is based on findings from the interim analyses of the phase III ELEVATE-TN and ASCEND (ACE-CL-309) studies, which showed that acalabrutinib either as a single agent or in combination significantly reduced the risk of disease progression or death compared with standard regimens. Regarding safety, the … (leggi tutto)
FDA Grants Priority Review to Avapritinib for GIST
Aug 7, 2019 – The FDA has granted a priority review designation to a new drug application (NDA) for avapritinib for the treatment of adult patients with PDGFRA exon 18–mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, as well as for patients with GIST in the fourth-line setting. Under the Prescription Drug User Fee Act, the FDA must make a decision on the NDA by February 14, 2020. “Patients with PDGFRA exon 18 mutant GIST and fourth-line … (leggi tutto)
FDA approves first therapy for rare joint tumor
Aug 2, 2019 – Today, the U.S. Food and Drug Administration granted approval to pexidartinib capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery. “TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause … (leggi tutto)
FDA Grants Bempegaldesleukin Plus Nivolumab Breakthrough Designation in Melanoma
Aug 1, 2019 – The FDA granted a breakthrough therapy designation to the combination of bempegaldesleukin (NKTR-214) and nivolumab for the treatment of patients with previously untreated unresectable or metastatic melanoma. The designation is based on results from a cohort of the ongoing phase I/II PIVOT-02 trial, in which the combination of bempegaldesleukin and nivolumab led to an overall response rate (ORR) of 53% by independent radiology review … (leggi tutto)
FDA Approves Pembrolizumab for PD-L1+ Esophageal Cancer
July 31, 2019 – The FDA has approved pembrolizumab for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (combined positive score [CPS] ≥10) as determined by an FDA-approved test, with disease progression after ≥1 prior line of systemic therapy. The approval is based on findings from the phase III KEYNOTE-181 and phase II KEYNOTE-180 trials, in which pembrolizumab led to … (leggi tutto)
FDA Approves Darolutamide for Nonmetastatic CRPC
July 31, 2019 – The FDA has approved darolutamide for the treatment of patients with nonmetastatic castration-resistant prostate cancer. The approval of the androgen receptor inhibitor is based on data from the phase III ARAMIS trial, in which darolutamide in combination with androgen deprivation therapy (ADT) led to a 59% reduction in the risk of metastases or death compared with placebo/ADT in this patient population (HR, 0.41; 95% CI, 0.34-0.50; 2-sided, P <.0001) … (leggi tutto)
Dall’ASCO
USPSTF Recommendation on Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer
Aug 22, 2019 – As reported in JAMA, the U.S. Preventive Services Task Force (USPSTF) recommended risk assessment and, if indicated, genetic counseling and testing for potentially harmful BRCA1/2 mutations in women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have ancestry associated with BRCA1/2 mutations. The recommendation is an update to the USPSTF 2013 recommendation. To inform the updated recommendation … (leggi tutto)
NCORP Expands to More Sites
Aug 20, 2019 – The National Cancer Institute (NCI) has awarded 53 grants to researchers in the NCI Community Oncology Research Program (NCORP) to conduct multisite cancer clinical trials and cancer care delivery studies in their communities. In addition to seven research hubs, these NCI grants went to 32 community sites and 14 minority/underserved community sites, which have assembled more than 1,000 affiliates across the country to carry out cancer research … (leggi tutto)
NCI Designations Propel Innovation at Two Prestigious Cancer Institutions
Aug 17, 2019 – Residents of Indiana now have a National Cancer Institute (NCI)-designated Comprehensive Cancer Center in their state, and Floridians have another designated Cancer Center in theirs. Both institutions, the Indiana University Melvin and Bren Simon Cancer Center (IU Simon Cancer Center) in Indianapolis and the University of Miami Sylvester Comprehensive Cancer Center (UM Sylvester), are OncLive® Strategic Alliance Partners. The NCI designations are … (leggi tutto)
ASCO Announces CancerLinQ Discovery® Research Support Grant Recipients
Aug 15, 2019 – The American Society of Clinical Oncology (ASCO) announced today the three recipients of its CancerLinQ Discovery® Research Support Grant. The awardees will undertake research projects using data from CancerLinQ Discovery®, an offering of ASCO’s CancerLinQ® initiative that provides de-identified data from cancer patients to academic researchers, government agencies, and others in the oncology community to generate practical knowledge that will … (leggi tutto)
USPSTF Recommendation on Screening for Pancreatic Cancer in Asymptomatic Adults
Aug 13, 2019 – As reported in JAMA, the U.S. Preventive Services Task Force (USPSTF), in a reaffirmation of its 2004 recommendation, has recommended against screening for pancreatic cancer in asymptomatic adults (a grade D recommendation). In developing the current recommendation, the USPSTF reviewed evidence on benefits and harms of screening, diagnostic accuracy of screening tests, and benefits and harms of treatment of screen- … (leggi tutto)
CAR T-Cell Therapy Coverage Decision Improves Medicare Beneficiary Access to Cancer Care
Aug 8, 2019 – “ASCO applauds the Centers for Medicare & Medicaid Services (CMS) for releasing a national coverage determination (NCD) on CAR T-cell therapy that provides increased access to an innovative cancer treatment to Medicare beneficiaries nationwide. The determination is largely consistent with ASCO’s principles for CAR T-cell therapy coverage, which support coverage for all Food and Drug Administration (FDA)-approved indications of this treatment … (leggi tutto)
NCCN Guidelines Set New Pace for Pediatric ALL
Aug 4, 2019 – With the recent publication of an inaugural set of guidelines for treatment of pediatric acute lymphoblastic leukemia (ALL), the National Comprehensive Cancer Network (NCCN) seeks to introduce standards to a branch of care long dominated by clinical trial protocols. These new standards are intended for managing different age groups and risk levels, youths with Philadelphia chromosome (Ph)-positive ALL, and toxicities, with an eye toward current and … (leggi tutto)
WHO Releases Report on the Global Tobacco Epidemic
Jul 30, 2019 – Many governments are making progress in the fight against tobacco, with 5 billion people today living in countries that have introduced smoking bans, warnings on packaging, and other effective tobacco control measures – four times more people than a decade ago. However, a new World Health Organization (WHO) report shows many countries are still not adequately implementing antitobacco policies that can save lives. The WHO Report on the Global Tobacco … (leggi tutto)
Dal mondo
TAS-102 Nabs Japanese Approval for Gastric Cancer
Aug 23, 2019 – The Japanese Ministry of Health, Labour and Welfare has approved TAS-102 (trifluridine/tipiracil) for the treatment of patients with unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy, according to Taiho Pharmaceutical Co., Ltd., the manufacturer of the oral agent. The approval was based on the phase III TAGS trial, in which TAS-102 reduced the risk of death by 31% compared with placebo in patients with … (leggi tutto)
Daratumumab/VMP Combo Approved in Japan for Frontline Myeloma
Aug 22, 2019 – The Japanese Ministry of Health, Labor and Welfare has approved daratumumab for use in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. The approval was based on the pivotal, open-label phase III ALCYONE study, in which daratumumab plus VMP demonstrated a 50% reduction in the risk of progression or death … (leggi tutto)
Pillole dall’Aifa
22 agosto 2019 – Aggiornamento sulla carenza del farmaco Mitomycin-C (Kyowa Kirin)
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