Braña, I. (Irene)

Filtering

20202

Settings

Author search.filters.isAuthorOfPublication.a257b7ae-346d-4f94-82b3-36089083b43c

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer
    (Elsevier, 2020) Jabbour, S. (Salma); Mathias, M. (Melissa); Feng, M. (Minjie); Naing, A. (Aung); Yoo, S.Y. (Suk-Young); Baranda, J. (Joaquina); Lowy, I. (Israel); Falchook, G.S. (Gerald S.); Rischin, D. (Danny); Stankevich, E. (Elizabeth); Gil-Martin, M. (Marta); Hou, J.Y. (June Y.); Yama-Dang, N.A. (N. Alice); González-Martín, A. (Antonio); Papadopoulos, K.P. (Kyriakos P.); Moore, K. (Kathleen); Fury, M.G. (Matthew G.); Cho, D. (Daniel); Fury, W. (Wen); Braña, I. (Irene); Formenti, S.C. (Silvia C.); Li, J. (Jingjin)
    Objectives: To characterize the safety, tolerability, and anti-tumor activity of cemiplimab as monotherapy or in combination with hypofractionated radiation therapy (hfRT) in patients with recurrent or metastatic cervical cancer. To determine the association between histology and programmed death-ligand 1 (PD-L1) expression. Methods: In non-randomized phase I expansion cohorts, patients (squamous or non-squamous histology) received cemiplimab 3 mg/kg intravenously every 2 weeks for 48 weeks, either alone (monotherapy cohort) or with hfRT during week 2 (combination cohort). Due to insufficient tissue material, PD-L1 protein expression was evaluated in commercially purchased samples and mRNA expression levels were analyzed from The Cancer Genome Atlas (TCGA). Results: Twenty patients enrolled in both cohorts in total; 10 had squamous histology. The most common adverse events of any grade were diarrhea, fatigue, and hypokalemia, occurring in 35%, 25%, and 25%, respectively. Objective response rate was 10% in each cohort; responders had squamous histology. Duration of response was 11.2 months and 6.4 months for the responder in the monotherapy and combination cohort, respectively. Irradiated lesions were not included in the response assessments. In separate archived specimens (N = 155), PD-L1 protein expression in tumor and immune cells was negative (<1%) more commonly in adenocarcinoma than in squamous tumors. PD-L1 mRNA levels were lower in adenocarcinoma than squamous cell tumors (1.2 vs 5.0 mean transcripts per million, respectively) in TCGA. Conclusions: Cemiplimab has activity in cervical squamous cell carcinoma. The phase I results, combined with results from other anti-PD-1 trials in cervical cancer and our biomarker analyses have informed the design of the ongoing phase III trial, with the primary overall survival hierarchical analyses being done first in patients with squamous histology.
  • Thumbnail Image
    Capturing Hyperprogressive Disease with Immune-Checkpoint Inhibitors Using RECIST 1.1 Criteria
    (AACR Journals, 2020) Matos, I. (Ignacio); Martin-Liberal, J. (Juan); García-Ruiz, A. (Alonso); Hierro, C. (C.); Ochoa-de-Olza, M. (María); Viaplana, C. (Cristina); Azaro, A. (Analia); Braña, I. (Irene); Mur, G. (Gemma); Ros, J. (Javier); Mateos, J. (José); Villacampa, G. (Guillermo); Berché, R. (Roger); Oliveira, M. (Mafalda); Alsina, M. (María); Elez, E. (Elena); Oaknin, A. (Ana); Muñoz-Couselo, E. (Eva); Carles, J. (Joan); Felip, E. (Enriqueta); Rodon, J. (Jordi); Tabernero, J. (Josep); Dienstmann, R. (Rodrigo); Pérez-López, R. (Raquel); Garralda, E. (Elena)
    Purpose: Most hyperprogression disease (HPD) definitions are based on tumor growth rate (TGR). However, there is still no consensus on how to evaluate this phenomenon. Patients and methods: We investigated two independent cohorts of patients with advanced solid tumors treated in phase I trials with (i) programmed cell death 1 (PD-1)/PD-L1 antibodies in monotherapy or combination and (ii) targeted agents (TA) in unapproved indications. A Response Evaluation Criteria in Solid Tumors (RECIST) 1.1-based definition of hyperprogression was developed. The primary endpoint was the assessment of the rate of HPD in patients treated with ICIs or TAs using both criteria (RECIST and TGR) and the impact on overall survival (OS) in patients who achieved PD as best response. Results: Among 270 evaluable patients treated with PD-1/PD-L1 inhibitors, 29 PD-1/PD-L1-treated patients (10.7%) had HPD by RECIST definition. This group had a significantly lower OS (median of 5.23 months; 95% CI, 3.97-6.45) when compared with the non-HPD progressor group (median, 7.33 months; 95% CI, 4.53-10.12; HR = 1.73, 95% CI, 1.05-2.85; P = 0.04). In a subset of 221 evaluable patients, 14 (6.3%) were categorized as HPD using TGR criteria, differences in median OS (mOS) between this group (mOS 4.2 months; 95% IC, 2.07-6.33) and non-HPD progressors (n = 44) by TGR criteria (mOS 6.27 months; 95% CI, 3.88-8.67) were not statistically significant (HR 1.4, 95% IC, 0.70-2.77; P = 0.346). Among 239 evaluable patients treated with TAs, 26 (10.9%) were classified as having HPD by RECIST and 14 using TGR criteria in a subset of patients. No differences in OS were observed between HPD and non-HPD progressors treated with TAs. Conclusions: HPD measured by TGR or by RECIST was observed in both cohorts of patients; however, in our series, there was an impact on survival only in the immune-checkpoint inhibitor cohort when evaluated by RECIST. We propose a new way to capture HPD using RECIST criteria that is intuitive and easy to use in daily clinical practice.