Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial.

BACKGROUND: Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Durvalumab versus placebo with chemoradiotherapy for locally advanced cervical cancer (CALLA): a randomised, double-blind, phase 3 trial.

BACKGROUND: Concurrent chemoradiotherapy has been the standard of care for locally advanced cervical cancer for over 20 years; however, 30-40% of treated patients have recurrence or progression within 5 years. Immune checkpoint inhibition has improved outcomes for patients with PD-L1 positive metastatic or recurrent cervical cancer. We assessed the benefit of adding durvalumab, a PD-L1 antibody, with and following chemoradiotherapy for locally advanced cervical cancer. METHODS: The CALLA randomised, double-blind, phase 3 trial included 105 hospitals across 15 countries. Patients aged at least 18 years with previously untreated locally advanced cervical cancer (adenocarcinoma, squamous, or adenosquamous; International Federation of Gynaecology and Obstetrics [FIGO] 2009 stage IB2-IIB lymph node positive, stage ≥III any lymph node status) and WHO or Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned (1:1) through an interactive web response system using a permuted block size of 4 to receive durvalumab (1500 mg intravenously once every 4 weeks) or placebo with and following chemoradiotherapy, for up to 24 cycles. Chemoradiotherapy included 45 Gy external beam radiotherapy at 5 fractions per week concurrent with intravenous cisplatin (40 mg/m2) or carboplatin (area under the concentration-time curve 2) once weekly for 5 weeks, followed by image-guided brachytherapy (high-dose rate, 27·5-30 Gy or low-dose/pulse-dose rate, 35-40 Gy). Randomisation was stratified by disease stage status (FIGO stage and node status) and geographical region. Chemoradiotherapy quality was continuously reviewed. The primary endpoint was progression-free survival, assessed by the investigator using Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03830866. FINDINGS: Between Feb 15, 2019, and Dec 10, 2020, 770 women were randomly assigned (385 to durvalumab and 385 to placebo; median age 49 years [IQR 41-57]). Median follow-up was 18·5 months (IQR 13·2-21·5) in the durvalumab group and 18·4 months (13·2-23·7) in the placebo group. At data cutoff, median progression-free survival had not been reached (95% CI not reached-not reached) for either group (HR 0·84; 95% CI 0·65-1·08; p=0·17); 12-month progression-free survival was 76·0% (71·3-80·0) with durvalumab and 73·3% (68·4-77·5) with placebo. The most frequently reported grade 3-4 adverse events in both groups were anaemia (76 [20%] of 385 in the durvalumab group vs 56 [15%] of 384 in the placebo group) and decreased white blood cells (39 [10%] vs 49 [13%]). Serious adverse events occurred for 106 (28%) patients who received durvalumab and 89 (23%) patients who received placebo. There were five treatment-related deaths in the durvalumab group (one case each of urinary tract infection, blood loss anaemia, and pulmonary embolism related to chemoradiotherapy only; one case of endocrine disorder related to durvalumab only; and one case of sepsis related to both durvalumab and chemoradiotherapy). There was one treatment-related death in the placebo group (pneumonia related to chemoradiotherapy). INTERPRETATION: Durvalumab concurrent with chemoradiotherapy was well tolerated in participants with locally advanced cervical cancer, however it did not significantly improve progression-free survival in a biomarker unselected, all-comers population. Concurrent durvalumab plus chemoradiotherapy warrants further exploration in patients with high tumoral PD-L1 expression. Rigorous monitoring ensured high chemoradiotherapy compliance with advanced technology and allowed patients to receive optimal care. FUNDING: AstraZeneca.

Recomendaciones clínicas para el manejo de pacientes oncológicos en el marco de la pandemia COVID-19 / Clinical Recommendations For The Management Of Cancer Patients In The Context Of The COVID-19 Pandemic

La enfermedad por la nueva cepa de Coronavirus (COVID-19) ha sido catalogada como una pandemia por la OMS. En el Perú, se decretó estado de emergencia nacional y aislamiento social obligatorio desde el 15 de marzo. Los sistemas de salud a nivel mundial han sufrido un gran impacto debido la infección por COVID-19, lo cual obligó a los sistemas de salud, sociedades y asociaciones médicas a diseñar estrategias de intervención priorizada para dar continuidad a la atención de los pacientes en áreas COVID-19 y áreas libres de COVID-19. El paciente con cáncer es catalogado como vulnerable y representa un factor de riesgo para complicaciones, como ingreso a unidad de cuidados intensivos, intubación y muerte temprana por infección por COVID-19. Es así como la Asociación de Médicos Ex-Residentes de Oncología Médica (AMEROM), ha realizado esfuerzos para poder realizar recomendaciones adaptables a nuestro sistema de salud, con la finalidad de dar continuidad a la atención priorizada de los pacientes con cáncer. Mediante la metodología modificada de consenso de expertos, bajo el sustento bibliográfico, se han generado recomendaciones en diferentes etapas de la pandemia, llegando a un consenso final con recomendaciones clínicas para el manejo de pacientes oncológicos en el marco de la pandemia COVID-19 en Perú, con el fin de brindar información útil para los profesionales de la salud. El presente artículo indica los procesos con los que se llegaron a los acuerdos para dictar las recomendaciones y generar el orden de prioridad adoptado por AMEROM.

The disease by the new coronavirus strain (COVID-19) has been classified as apandemic by the WHO. In Peru, a state of national emergency and compulsory socialisolation had been declared since 15 March. Global health systems have been greatlyimpacted by COVID-19, which forced health systems, societies and medicalassociations to design prioritized intervention strategies to provide continuity of patientcare in infected areas and COVID-19-free areas. A cancer patient is classified asvulnerable and represents a risk factor for complications due to COVID-19, such asadmission to the intensive care unit, intubation, and early death due to infection due toCOVID-19. This is how the Asociación de Médicos Ex Residentes de OncologíaMédica (AMEROM), has endeavored to give recommendations adaptable to our healthsystem, to continue with the prioritized care of cancer patients. Through the modifiedmethodology of expert consensus, based on the literature, recommendations have beengenerated at different stages of the pandemic, reaching a final consensus of clinicalrecommendations for the management of cancer patients in the framework of theCOVID-19 pandemic in Peru, to provide useful information to health professionals.This article indicates the processes by which agreements were reached to makerecommendations and generate the order of priority adopted by AMEROM.

Inmunizaciones: lo viejo, lo nuevo y lo por venir / Immunizations: the old, the new and the for coming

Sobre un tema tan apasionante y donde el avance del conocimiento se está efectuando a pasos tan agigantados, sin duda podría escribirse mucho. Esta breve síntesis sólo pretende dar una idea global acerca del problema y las principales líneas de investigación que intentan lograr mayor eficiencia, menores riesgos y solucionar el problema de controlar enfermedades que aún permanecen sin un medio eficiente para conseguirlo