PMID- 37774508
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231109
IS  - 2059-7029 (Electronic)
IS  - 2059-7029 (Linking)
VI  - 8
IP  - 5
DP  - 2023 Oct
TI  - Phase II study of capecitabine-based concomitant chemoradiation followed by 
      durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the 
      PANDORA trial.
PG  - 101824
LID - S2059-7029(23)01059-1 [pii]
LID - 10.1016/j.esmoop.2023.101824 [doi]
LID - 101824
AB  - BACKGROUND: This study investigated the efficacy of chemoradiotherapy (CRT) 
      followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer. 
      PATIENTS AND METHODS: The PANDORA trial is a prospective, phase II, open-label, 
      single-arm, multicenter study aimed at evaluating the efficacy and safety of 
      preoperative treatment with durvalumab (1500 mg every 4 weeks for three 
      administrations) following long-course radiotherapy (RT) plus concomitant 
      capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine 
      administered at 825 mg/m(2) twice daily). The primary endpoint was the 
      pathological complete response (pCR) rate; secondary endpoints were the 
      proportion of clinical complete remissions and safety. The sample size was 
      estimated assuming a null pCR proportion of 0.15 and an alternative pCR 
      proportion of 0.30 (alpha = 0.05, power = 0.80). The proposed treatment could be 
      considered promising if >/=13 pCRs were observed in 55 patients (EudraCT: 
      2018-004758-39; NCT04083365). RESULTS: Between November 2019 and August 2021, 60 
      patients were accrued, of which 55 were assessable for the study's objectives. 
      Two patients experienced disease progression during treatment. Nineteen out of 55 
      eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). 
      Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred 
      in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase 
      increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients 
      (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were 
      endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and 
      gastrointestinal toxicity (transaminase increase, nausea, diarrhea, 
      constipation). CONCLUSION: This study met its primary endpoint showing that CRT 
      followed by durvalumab could increase pCR with a safe toxicity profile. This 
      combination is a promising, feasible strategy worthy of further investigation.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Grassi, E
AU  - Grassi E
AD  - Medical Oncology Unit, "Degli Infermi" Hospital, AUSL della Romagna, Faenza.
FAU - Zingaretti, C
AU  - Zingaretti C
AD  - Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio 
      dei Tumori (IRST) "Dino Amadori", Meldola.
FAU - Petracci, E
AU  - Petracci E
AD  - Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio 
      dei Tumori (IRST) "Dino Amadori", Meldola.
FAU - Corbelli, J
AU  - Corbelli J
AD  - Medical Oncology Unit, "Degli Infermi" Hospital, AUSL della Romagna, Faenza.
FAU - Papiani, G
AU  - Papiani G
AD  - Medical Oncology Unit, "Santa Maria delle Croci" Hospital, AUSL della Romagna, 
      Ravenna.
FAU - Banchelli, I
AU  - Banchelli I
AD  - Pathology Unit, "Santa Maria delle Croci" Hospital, AUSL della Romagna, Ravenna.
FAU - Valli, I
AU  - Valli I
AD  - Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio 
      dei Tumori (IRST) "Dino Amadori", Meldola.
FAU - Frassineti, G L
AU  - Frassineti GL
AD  - Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori 
      (IRST) "Dino Amadori", Meldola.
FAU - Passardi, A
AU  - Passardi A
AD  - Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori 
      (IRST) "Dino Amadori", Meldola.
FAU - Di Bartolomeo, M
AU  - Di Bartolomeo M
AD  - Gastroenterological Medical Oncology, Fondazione IRCCS Istituto Nazionale dei 
      Tumori, Milan.
FAU - Pietrantonio, F
AU  - Pietrantonio F
AD  - Gastroenterological Medical Oncology, Fondazione IRCCS Istituto Nazionale dei 
      Tumori, Milan.
FAU - Gelsomino, F
AU  - Gelsomino F
AD  - Department of Oncology and Hematology, Division of Oncology, University Hospital 
      of Modena, Modena.
FAU - Carandina, I
AU  - Carandina I
AD  - Department of Medical Oncology, "Sant'Anna" University Hospital of Ferrara, 
      Ferrara.
FAU - Banzi, M
AU  - Banzi M
AD  - Medical Oncology Unit, "Santa Maria Nuova" Hospital, AUSL-IRCCS di Reggio Emilia, 
      Reggio Emilia.
FAU - Martella, L
AU  - Martella L
AD  - Department of Medical Oncology, "Sant'Anna" University Hospital of Ferrara, 
      Ferrara.
FAU - Bonetti, A V
AU  - Bonetti AV
AD  - Department of Medical Oncology, "Mater Salutis" Hospital, Legnago.
FAU - Boccaccino, A
AU  - Boccaccino A
AD  - Medical Oncology Unit, "Santa Maria delle Croci" Hospital, AUSL della Romagna, 
      Ravenna.
FAU - Molinari, C
AU  - Molinari C
AD  - Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 
      "Dino Amadori", Meldola.
FAU - Marisi, G
AU  - Marisi G
AD  - Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 
      "Dino Amadori", Meldola.
FAU - Ugolini, G
AU  - Ugolini G
AD  - General Surgery Unit, "Santa Maria delle Croci" Hospital, AUSL della Romagna, 
      Ravenna, Italy.
FAU - Nanni, O
AU  - Nanni O
AD  - Unit of Biostatistics and Clinical Trials, IRCCS Istituto Romagnolo per lo Studio 
      dei Tumori (IRST) "Dino Amadori", Meldola.
FAU - Tamberi, S
AU  - Tamberi S
AD  - Medical Oncology Unit, "Degli Infermi" Hospital, AUSL della Romagna, Faenza; 
      Medical Oncology Unit, "Santa Maria delle Croci" Hospital, AUSL della Romagna, 
      Ravenna. Electronic address: stefano.tamberi@auslromagna.it.
LA  - eng
SI  - ClinicalTrials.gov/NCT04083365
SI  - EudraCT/2018-004758-39
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20230927
PL  - England
TA  - ESMO Open
JT  - ESMO open
JID - 101690685
RN  - 6804DJ8Z9U (Capecitabine)
RN  - 28X28X9OKV (durvalumab)
RN  - EC 2.6.1.- (Transaminases)
SB  - IM
MH  - Humans
MH  - Capecitabine/pharmacology/therapeutic use
MH  - *Neoadjuvant Therapy
MH  - Prospective Studies
MH  - *Rectal Neoplasms/drug therapy/pathology
MH  - Chemoradiotherapy/adverse effects
MH  - Diarrhea/chemically induced
MH  - Transaminases/therapeutic use
PMC - PMC10594026
OTO - NOTNLM
OT  - durvalumab
OT  - immunotherapy
OT  - locally advanced rectal cancer
OT  - neoadjuvant strategy
EDAT- 2023/09/30 09:42
MHDA- 2023/10/30 06:46
PMCR- 2023/09/27
CRDT- 2023/09/29 18:04
PHST- 2023/05/16 00:00 [received]
PHST- 2023/08/17 00:00 [revised]
PHST- 2023/08/19 00:00 [accepted]
PHST- 2023/10/30 06:46 [medline]
PHST- 2023/09/30 09:42 [pubmed]
PHST- 2023/09/29 18:04 [entrez]
PHST- 2023/09/27 00:00 [pmc-release]
AID - S2059-7029(23)01059-1 [pii]
AID - 101824 [pii]
AID - 10.1016/j.esmoop.2023.101824 [doi]
PST - ppublish
SO  - ESMO Open. 2023 Oct;8(5):101824. doi: 10.1016/j.esmoop.2023.101824. Epub 2023 Sep 
      27.