ESTRO 2023

Session Item

Saturday

May 13

10:30 - 11:30

Plenary Hall

Upper GI

Chair: Marianne Nordsmark, Denmark;

Co-Chair: , The Netherlands

Session Code: 1215

Session Type: Proffered Papers

Track: Clinical

11:10 - 11:20

SCOPE2 PET: continuing CisCap v switch to CarPac in PET non-responders on dCRT for esophageal cancer

Somnath Mukherjee, United Kingdom

Presentation Number: OC-0103

Abstract

Abstract Title:

SCOPE2 PET: continuing CisCap v switch to CarPac in PET non-responders on dCRT for esophageal cancer

Authors:

Somnath Mukherjee¹, Chris Hurt², Sarah Gwynne³, Lisette Nixon², Sarah Bridges², Richard Adams², Ganesh Radhakrishna⁴, Tim Maughan⁵, Marie-Clare Hunter², Rashmi Kumar², Rajarshi Roy⁶, Christopher Jones⁷, Christopher Marshall⁸, Kevin Bradley⁸, Debbie Callaghan⁶, Simon Gollins⁹, Hamid Sheikh⁴, Andrew Bateman¹⁰, Stephen Falk¹¹, Bethan Tranter¹², Geraint John Lewis¹³, Emiliano Spezi¹⁴, Maria Hawkins¹⁵, Tom Crosby¹⁶

¹Oxford University Hospital NHS Foundation Trust, Oncology, Oxford, United Kingdom; ²Cardiff University, Centre For Trials Research, Cardiff, United Kingdom; ³Swansea Bay University Health Board, Oncology, Swansea, United Kingdom; ⁴The Christie NHS Foundation Trust, Oncology, Manchester, United Kingdom; ⁵University of Oxford, Oncology, Oxford, United Kingdom; ⁶Hull University Teaching Hospitals NHS Trust, Oncology, Hull, United Kingdom; ⁷University of Cambridge, Oncology, Cambridge, United Kingdom; ⁸Cardiff University, Wales Research and Diagnostic PET Imaging Centre, Cardiff, United Kingdom; ⁹Betsi Cadwaladr University Health Board, Oncology, Rhyl, United Kingdom; ¹⁰University Hospital Southampton NHS Foundation Trust, Oncology, Southampton, United Kingdom; ¹¹University Hospitals Bristol NHS Foundation Trust, Oncology, Bristol, United Kingdom; ¹²Velindre University NHS Trust, Pharmacy, Cardiff, United Kingdom; ¹³Velindre University NHS Trust, Medical Physics, Cardiff, United Kingdom; ¹⁴Cardiff University, School of Engineering, Cardiff, United Kingdom; ¹⁵University College London, Oncology, London, United Kingdom; ¹⁶Velindre University NHS Trust, Oncology, Cardiff, United Kingdom

Show Affiliations

Purpose or Objective

The randomised phase II/III SCOPE2 is investigating two questions in patients with oesophageal squamous carcinoma (SCC) and adenocarcinoma (ACA) receiving definitive chemoradiation (dCRT): 1) does high dose RT (60Gy/25#) improve OS compared to standard dose (50Gy/25#) and 2) In PET non-responders (based on FDG-PET-CT on day 14 of cycle 1 induction chemotherapy) does switching chemotherapy from Cisplatin-Capecitabine (CisCap) to Carboplatin-Paclitaxel (CarPac) after 1 cycle improve treatment failure-free survival (TFFS) at 24 weeks. The dose escalation component (randomised phase III) is still ongoing; here, we report results of the PET substudy

Material and Methods

Design: The PET substudy is a randomised Phase II component of a multicentre, open label, parallel, 2x2 (four arm) factorial study.

Key Eligibility: Histologically confirmed cancer oesophagus/GOJ with <2cm extension into the stomach; selected for dCRT by a designated Multidisciplinary Team Meeting; age>=18; WHO PS 0-1; T1-4 and N+/-; total disease length ≤13cm. Baseline FDG-PET SUVmax ≥ 5 (performed within 5 weeks prior to start of treatment).

Procedures: Repeat PET performed on Day 14 of 1st cycle of induction CisCap. Non-responders (drop in SUVmax<35%) were randomized to continue CisCap or switch to CarPac for cycle 2 followed by concurrent CRT with same chemotherapy. All patients were also randomized between 50Gy and 60Gy arms.

Statistical Consideration: PET substudy was powered separately in SCC and ACA. For SCC 86 non-responders were required to detect a 20% improvement in 24wk TFFS (55% to 75% with CarPac; chi square, 87% power, 0.2 one sided alpha). For ACA, 27 patients would detect an improvement in 24 week TFFS from 55% with to 85% with CarPac (chi square, 80% power, 0.20 one sided alpha).

RT Quality Assurance: An associated RTQA program ensured high quality RT was delivered.

Funding: Cancer Research UK (A17606) and

Trial Sponsor: Velindre University NHS Trust.

Results

IDMC stopped PET substudy in Aug 2021 on the grounds of futility and possible harm. 63/103 (61%) participants were non-responders (SCC=52/83; ACA=11/20) of whom 32 were randomised to continue CisCap and 31 switched to CarPac. The 24 week TFFS in the SCC cohort was no better in responders (who continued CisCap) than non-responders who stayed on CisCap or switched to CarPac (78.6% v 92.6% v 68%). In non-responders (SCC cohort) both 24-week TFFS [25/27(92.6%) vs 17/25(68%) p=0.028] and OS (42.5 mo v 20.4mo, adjusted HR 0.36, p=0.018) favoured CisCap over CarPac. PFS favoured CisCap but was non-significant (34.6 mo v 19.4mo, HR 0.58, p=0.15). Similar trend was seen in ACA (p=NS). Grade 3 /4 toxicity rate was comparable between arms [CarPac 22/31 (71.0%) vs CisCap 21/31 (67.7%)].

Conclusion

Early PET response based on proposed SUVmax cut-off was not prognostic and did not predict treatment failure. Chemo-switch based on early PET response using proposed cut-off cannot be recommended in this setting. A better discriminator for early treatment failure is required.