ICHNO-ECHNO 2022 - Abstract Book

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ICHNO-ECHNO 2022

Conclusion We confirm that unequivocal rENE has high inter-rater reliability and is prognostically important in NPC in a diverse Western cohort. We propose classifying any unequivocal rENE as cN3. The inclusion of rENE in the cN classification appears to improve risk stratification to facilitate segregation into patient’s sub-groups who may benefit from different treatment approaches or clinical trial entry in this non-endemic population.

Symposium: The role of IO in the curative setting

SP-0030 IO prior to local treatment Lotje Zuur The Netherlands

Abstract not availanle

SP-0031 Why combining radiotherapy and IO is challenging

K. Harrington 1

1 The Institute of Cancer Research/Royal Marsden Hospital, Division of Radiotherapy and Imaging, LONDON, United Kingdom

Abstract Text Until recently, radiation therapy (RT) was viewed almost exclusively through the lens of tumour cell-autonomous events, such that successful therapy was seen to depend on inflicting sufficient breaks in nuclear DNA above an unspecified threshold that exceeded the cell’s capacity for repair. Rapidly evolving understanding of the importance of non-tumour cell-autonomous, immunological effects of RT-induced cell death in the context of a complex tumour microenvironment has modified this view. We now appreciate that responses to RT depend not only on direct tumour cell killing, but also on the immune system: loco-regional RT can trigger abscopal, immune-mediated responses at neighbouring and/or distant unirradiated sites, while patients who are pathologically or iatrogenically immunosuppressed may derive less benefit from RT. In the last decade, successes with immune checkpoint inhibition (ICPI) have revolutionised the palliative management of many relapsed/metastatic cancers in the first- and second-line settings. Consequently, there has been a drive to evaluate ICPI in combination with radiation/chemo-radiation (C-RT) in the curative setting (and in patients with relapsed/(oligo/poly)metastatic disease). In the context of head and neck cancer (HNC), there have been a number of randomised studies of combined approaches with RT/C-RT plus ICPI that have recently reported negative results and these should cause us to re-evaluate assumptions relating to the RT-immunotherapy paradigm. Javelin Head and Neck-100 study was a randomised, double-blind, placebo-controlled, multi-centre phase 3 study of avelumab versus placebo in patients with histologically confirmed, previously untreated locally-advanced HNC. The primary endpoint of prolonging progression-free survival (PFS) with avelumab + CRT followed by avelumab maintenance was not met. Similarly, the REACH study [NCT02999087] in which the experimental arm was combined radiotherapy/avelumab/cetuximab versus standard-of-care C-RT (in platin-eligible patients) and bioradiotherapy (in platin- inelegible patients) failed to demonstrate improvement in PFS. The Pembro-Rad study (GORTEC 2015-01) randomised patients with HNC who were unfit to receive platin-based C-RT to RT plus either pembrolizumab or cetuximab. The primary endpoint of loco-regional control at 15 months was not significantly different between study arms (59% cetux-RT versus 60% pembro-RT). On a brighter note, in an approach not based on ICPI, GORTEC also evaluated the SMAC mimetic (Debio- 1143, Xevinapant) in a placebo-controlled trial [NCT02022098] in patients receiving C-RT. The phase II trial showed a marked improvement in median PFS in favour of the Xevinapant plus C-RT arm (not reached versus 16.9 months). This study has proceeded to the phase III Trilynx study [NCT04459715]. Other approaches, including comparison of C-RT with either pembrolizumab or placebo (KEYNOTE-412/NCT03040999) or adjuvant atezolizumab following definitive CRT (ImVOKE- 10/NCT03452137) are also being tested. The clinical studies outlined above highlight a number of challenging, unresolved issues relating to the use of RT- immunotherapy combinations. These include: radiation dose-fractionation; volume of irradiated tissues; schedule of immunotherapy relative to RT/C-RT; and optimal choice of immunotherapy agent(s). These matters will be discussed in detail during the presentation.

SP-0032 The role of IO in the adjuvant setting Lisa Licitra Italy

Abstract not available