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Clinical Trial
. 2023 Oct;8(5):101824.
doi: 10.1016/j.esmoop.2023.101824. Epub 2023 Sep 27.

Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial

E Grassi  1 , C Zingaretti  2 , E Petracci  2 , J Corbelli  1 , G Papiani  3 , I Banchelli  4 , I Valli  2 , G L Frassineti  5 , A Passardi  5 , M Di Bartolomeo  6 , F Pietrantonio  6 , F Gelsomino  7 , I Carandina  8 , M Banzi  9 , L Martella  8 , A V Bonetti  10 , A Boccaccino  3 , C Molinari  11 , G Marisi  11 , G Ugolini  12 , O Nanni  2 , S Tamberi  13
Affiliations
Clinical Trial

Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial

E Grassi et al. ESMO Open. 2023 Oct.

Abstract

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/m2 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 (α = 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.

Keywords: durvalumab; immunotherapy; locally advanced rectal cancer; neoadjuvant strategy.

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Figures

Figure 1
Figure 1
Study scheme. CRT, chemoradiotherapy; CT, computed tomography; MRI, magnetic resonance imaging; RT, radiotherapy; wk, week. aDuration of standard CRT: 5-5.5 weeks according to RT fractions.
Figure 2
Figure 2
Study flow diagram. COVID-19, coronavirus disease 2019.
See this image and copyright information in PMC

References

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