abstracts Annals of Oncology

885P Different patterns of treatment failure between p16+ and 886P Retrospective multicentric survival analysis of patients
p16- patients affected by oropharyngeal carcinoma (OPC) receiving TPEx regimen (docetaxel, platinum and
undergoing (chemo)radiation cetuximab) as first line treatment of recurrent or metastatic
squamous cell carcinoma of the head and neck
R. Gili1, P. Bossi2, L. Lalli3, L.F.L. Licitra4, M. Maddalo5,
J. Cacicedo Fernandez de Bobadilla6, N. facchinetti7, A. Garcia Castano8, L. Libert1, C. Abdeddaim2, K. Saleh3, C. Even4, S. Duplomb5, J. Dubreuil6,
R. Mesia Nin9, P. Bonomo10, G. Sanguineti11, P. Franco12, A. Argiris13, A. Psyrri14, A. Rambeau7, E. Guiard8, Y. Pointreau9, N. Olympios10, C. Moldovan10, E. Lévêque11,
E. Orlandi15 F. Clatot12
1
Oncology Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 2Med- 1
Centre Henri Becquerel, Rouen, France; 2Medical Oncology, Centre Oscar Lambret,
ical Oncology Department, IRCCS Humanitas Research Hospital, Milan, Italy; Lille, France; 3Medical Oncology, Gustave Roussy - Cancer Campus, Villejuif, France;
3 4
Oncology Department, Fondazione IRCCS - Istituto Nazionale dei Tumori, Milan, Italy; Head and Neck Oncology Department, Institut Gustave Roussy, Villejuif, France;
4 5
Head and Neck Medical Oncology Unit, Fondazione IRCCS - Istituto Nazionale dei Medical Oncology, Hôpital de la Croix-Rousse, Lyon, France; 6Medical oncology,
Tumori, Milan, Italy; 5Radiotherapy, ASST Spedali Civili di Brescia, Brescia, Italy; Hospices Civiles de Lyon - HCL - Lyon University Hospital Center, Lyon, France; 7Medical
6
Radiotherapy, Universidad del País Vasco (UPV/EHU), Leioa, Spain; 7Radiotherapy, oncology, Centre Francois Baclesse, Caen, France; 8Oncology Department, Centre
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 8Oncology Department, Francois Baclesse, Caen, France; 9Radiation Oncology, Centre Jean Bernard, Le Mans,
HUMV - Hospital Universitario Marques de Valdecilla, Santander, Spain; 9Medical France; 10Medical Oncology, Centre Henri Becquerel, Rouen, France; 11Biostatistics,
Oncology Department, ICO - Institut Català d’Oncologia - Hospital Duran i Reynals, Centre Henri Becquerel, Rouen, France; 12Medical Oncology Department, Centre Henri
Hospitalet De Llobregat, Spain; 10Radiation Oncology, Azienda Ospedaliero-Uni- Becquerel, Rouen, France
versitaria Careggi, Florence, Italy; 11Radiotherapy, IRCCS - Regina Elena National
Cancer Institute, Rome, Italy; 12Dipartimento di Oncologia, University of Turin, Turin, Background: TPEx regimen is a first line treatment option for recurrent or metastatic
Italy; 13Medical Oncology Department, Hygeia Hospital, Marousi, Greece; 14Internal head and neck squamous cell carcinoma (R/M HNSCC) if PD-L1 status is negative, or in
Medicine/Medical Oncology, Attikon University Hospital, Haidari, Greece; 15Clinical cases of high tumor burden. We sought to evaluate the survival rates of patients (pts)
Department, Centro Nazionale di Adroterapia Oncologica - CNAO, Pavia, Italy receiving TPEx as first line treatment for R/M HNSCC, particularly since the advent of
immunotherapy (IO) as second line therapy.
Background: The available data regarding different patterns of recurrence (DPR)
Methods: This multicentric retrospective study included pts who received between
between p16+ and p16- OPC patients (pts) are conflicting, and the present study aims
2018 and June 2023 at least the first day of a first cycle of TPEx (docetaxel 75 mg/m2;
at clarifying it.
cisplatin 75 or carboplatin AUC5; cetuximab 400 induction/250 weekly), with a per-
Methods: We retrospectively collected data on anyT, anyN, M0 OPCs treated with formance status of 0 or 1. The primary endpoint was overall survival (OS), i.e, the time
definitive IMRT (66-72 Gy)  systemic therapy in 14 South-European Centres from from start of treatment to death from any cause. Secondary end-points were: pro-
2007 to 2019 evaluating DPR (incidence of distant (DR) and/or locoregional recur- gression free survival under TPEx (PFS1), rate of patients exposed to IO after TPEx, PFS
rence (LR)) between p16+ and p16- pts and among p16+ subgroups. of pts receiving IO after TPEx (PFS2), OS and PFS according to CPS (<1 or  1) when
available.
Results: We analyzed 674 pts with a median follow-up time of 6 (5.7-6.3) years
(CI 95%). The DPR between p16+ and p16- pts are reported in the table. In the p16+ Results: 204 pts were included, mainly men (86%), previously treated for localized
group the incidence of exclusive DR or DR +/- LR was greater than the p16- cohort HNSCC (78%) and relapsing beyond 6 months after the end of localized treatment
(38.5% vs 28.4% and 51.3% vs 35.8%), while p16- OPCs experienced more exclusive LR (69%). 32% of pts had clinically threatening disease and 7% had liver metastases. CPS
or LR +/- DR (64.2% vs 48.7% and 71.6% vs 61.5%). Subgroup analyses of p16+ OPCs was available for 88 pts (43%). Pts were treated with a median of 4 cycles of TPEx,
by smoking history (>10 pack-years (PY), <10 PY, never smokers (NS)) showed that followed by cetuximab maintenance for 154 pts (75%). Overall, 148 pts (73%) were
the statistical difference in the DPR between p16+ and p16- holds true only when exposed to IO after TPEx, either as a second line treatment (68%) or third line or more
>10 PY p16+ pts were included in the analysis. Actually, the proportions of exclusive (5%). After a median follow-up of 35.8 months, median OS was 17.9 months. Median
DR (and DR +/- LR) is greater in the >10 PY p16+ group (43.5% and 58.7%) when PFS1 was 6.0 months. Median PFS2 on IO was 2.3 months, and median time from
compared with <10 PY (36.4% and 45.5%) and NS (28.6% and 38.1%) p16+ pts. progression on IO to death was 5.7 months (IQR 2.2-10.8). In multivariate analysis,
clinically threatening disease and the use of carboplatin instead of cisplatin remained
Conclusions: p16- and p16+ OPCs showed DPR after (chemo)radiation, with a higher
significantly associated with OS (HR 1.9 CI 1.2-2.8; HR 1.5 CI 1.0-2.1, respectively).
risk of LR and DR for p16- and p16+ respectively, with potential implications on both
When CPS was available, a multivariate analysis did not kept CPS as significantly
the pattern of observation after treatment and the salvageability of clinical failures.
associated with OS.
Surprisingly, the different behavior of p16+ OPCs is mostly observed in heavy smokers,
while oligo/no smokers have a pattern of recurrence more similar to p16- OPCs. Conclusions: The median OS of 17.9 months in this multicentric cohort under TPEx as
first line treatment for R/M HNSCC compares favorably with historical data. Most pts
Funding: Has not received any funding.
(73%) were exposed to IO after TPEx.
Disclosure: All authors have declared no conflicts of interest.
Legal entity responsible for the study: The authors.
https://doi.org/10.1016/j.annonc.2024.08.946 Funding: Has not received any funding.
Disclosure: C. Abdeddaim: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, Merck;
Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD; Financial Interests, Institutional,
Advisory Board: MSD; Financial Interests, Institutional, Local PI: GSK, Debio Pharm, MSD, Zentalis;
Financial Interests, Institutional, Coordinating PI: Epizyme. C. Even: Financial Interests, Personal,
Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory
Board: F Star Therapeutics, Novartis, Elevar, Bicara, PDS Biotechnology, GSK, Merus; Financial In-
terests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala,
Gilead, GSK, Beigene, Takeda, Genmab, Seagen, Nykode; Financial Interests, Institutional, Coordi-
nating PI: BMS, Novartis, Sanofi. All other authors have declared no conflicts of interest.

https://doi.org/10.1016/j.annonc.2024.08.947

Table: 885P DPR in OPCs

p16 e p16 + total p16+ NS p16+ <10 PY p16+ (NS + <10 PY) p16+ >10 PY

n pts 249 425 146 65 211 214
Recurrence 109 78 21 11 32 46
Exclusive DR 31/109 - 28.4% 30/78 - 38.5% 6/21 - 28.6% 4/11 - 36.4% 10/32 - 31.3% 20/46 - 43.5%
DR +/- LR 39/109 - 35.8% 40/78 - 51.3% 8/21 - 38.1% 5/11 - 45.5% 13/32 - 40.6% 27/46 - 58.7%
Exclusive LR 70/109 - 64.2% 38/78 - 48.7% 13/21 - 61.9% 6/11 - 54.5% 19/32 - 59.4% 19/46 - 41.3%
LR +/- DR 78/109 - 71.6% 48/78 - 61.5% 15/21 - 71.4% 7/11 - 63.6% 22/32 - 68.7% 26/46 - 56.5%

Volume 35 - Issue S2 - 2024 S631