The work of our team at ESMO 2023

The ESMO Congress is a highly influential oncology platform for clinicians, researchers, patient advocates, journalists and healthcare industry representatives from all over the world. https://www.esmo.org/

Several projects in which we collaborated are presented this year:

The two oral communications will focus on results concerning:

• Impact of a minimal versus CT-scan-based follow-up on patient-reported outcomes for completely resected non-small cell lung cancer (NSCLC) in phase III IFCT-0302 trial. Presented by G EBERST¹
• OMITting frontline chemotherapy in head and neck cancer (HNSCC) patients with 1-3 oligometastases using stereotactic ablative radiotherapy (SABR), the GORTEC 2014-04 “OMET” randomized phase II trial. Presented by J THARIAT²

Four posters will relate the results concerning:

• DCF versus doublet chemotherapy as first-line treatment of advanced squamous anal cell carcinoma: A multicenter propensity score matching study. Presented by C BORG³
• Pain response and health-related quality of life (HRQL) analysis in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel every 2 weeks (16 mg/m2) versus every 3 weeks (25 mg/m2) in the CABASTY phase III trial. Presented by S OUDARD⁴
• Management of biliary tract cancers in early onset patients: A French multicenter real-life study from the ACABI-PRONOBIL cohort. Presented by A LEBEAUD⁵
• Genomic profiling of small bowel adenocarcinoma: A pooled analysis. Presented by T APARICIO⁶

1 IFCT-0302

G. Eberst, J. Henriques, M. Monchatre, E. Giroux-Leprieur, E. Kelkel, A. BizieuxThaminy, P. Ravier, P. Thomas, S. Bayle, C. Audigier Valette, H. Berard, F. Desliers, A. Lagrange, P. Bonnefoy, A. Langlais, D. Vernerey, A. Anota, F. Morin, V. Westeel

Background: The IFCT-0302 trial was a randomized multicenter trial, which found no benefit in overall survival in adding chest CT-scan and fiberoptic bronchoscopy (optional for adenocarcinomas) to a follow-up based on physical examination and chest x-ray in resected NSCLC. We present the results of patient-reported outcomes (PROs), a secondary endpoint of the IFCT-0302 trial.

Methods: PROs consisted of Health-Related Quality of Life (HRQoL), assessed using the Short Form-12 (SF-12) questionnaire, and a penibility visual analogue scale (between 0 and 10), at randomization, every 6 months during 2 years and annually until 5 years or until disease progression or second primary cancer or death if they occurred before 5 years. Time to deterioration, used to analyze longitudinal HRQoL data, was defined as the interval between randomization and the occurrence of the first clinically relevant deterioration (5 points) compared to the HRQoL score at baseline.

Results: Between January 2005 and November 2012, 1775 patients were randomized in the IFCT-0302 trial. At baseline, 756 of the 888 patients (85.1%) in the minimal follow-up group had at least one HRQoL score available, and 747 of 887 (84.2%) in the CT-based follow-up group. 80.8% and 75.6% of patients completed questionnaires up to one year, respectively. There was no difference between groups in time to deterioration for the 2 dimensions of the SF-12 questionnaire: mental dimension [HR (the minimal follow-up group vs. the CT-based follow-up group): 0.92; 95%CI (0.80; 1.15); p=0.64] and physical dimension [HR: 0.87; 95%CI (0.71 ; 1.06) ; p=0.19]. Penibility was statistically greater in the CT-based follow-up group (p<0.0001), and was related to fiberoptic bronchoscopy.

Conclusions: Analysis of PROs in the IFCT-0302 trial demonstrated that adding thoracic CT-scan in the follow-up after resection of NSCLC did not influence HRQoL but penibility was increased, due to fiberoptic bronchoscopy.

Clinical trial identification NCT00198341. Legal entity responsible for the study IFCT. Funding French Health Ministry (PHRC-K), IFCT.

2 OMET

J. Thariat, M. Bosset, A. Falcoz, D. Vernerey, Y. Pointreau, S. Racadot, J.C. Faivre, J. Castelli, S. Guihard, F. Huguet, S. Chapet, Y. Tao, J. Bourhis, X.S. Sun

Background: Most trials in metastatic HNSCC compare systemic therapies; HNSCC were underrepresented in the few multihistology SABR trials; none has assessed SABR-alone vs chemo-SABR in often frail/heavily-pretreated HNSCC patients. The GORTEC 2014-04 phase IIR study assesses impact on survival without definitive quality of life (1yOS-QoL) deterioration of omitting frontline chemotherapy in oligometastatic HNSCC patients (pts) by using SABR alone.

Methods: SABR-alone (experimental arm) or chemo (SOC Extreme)-SABR to 1-3 metastases (mets) was evaluated using survival, PFS, definitive QoL deterioration (global, 10 points), toxicities (highest-grade/patient), QoL dimensions. Salvage treatments were left to physician’s appreciation (repeat SABR allowed).

Results: 69 pts treated at 11 centers in 2016-22, male 81.2%, mean age 62.7, had lung-only mets in 57 (82.6%), isolated mets in 40 (58.0%). Median baseline global QoL score was 66.7 (Q1-Q3 50.0-83.3). Of 57 pts eligible for 1yOS-QoL (QoL & follow-up missing in 10 & 2 pts/69), it was equivalent in both arms, with better Kaplan-Meier estimates of physical functioning & cough score deterioration-free survival with SABR-alone. In ITT analysis (69 pts), 1-year & median survival were 63.4 (95%CI 47.6-84.5), 47.2 with SABR-alone vs 61.7 (CI 46.2-82.4) & 42.3 months (m) with chemo-SABR. Median follow-up was 55.3m (CI 42.5-72.1) & 45.4m (CI 36.7-69.1) in the SABR-alone & chemo-SABR arms. One-year PFS rate were 38.2% with SABR-alone & 53.3% with chemo-SABR (1st CT done earlier in SABR-alone arm, p NS). Following relapse (N=58, 48 pts), 16 (10 in chemo-SABR, 6 SABR-alone arms) new out-of-field lesions and 1 in-field (in SABR-arm) mets were retreated with SABR-alone (17/58, 29.3%). Rates of all grade toxicities were 43/69 (62.3%): 10/34 (29.4%) with SABR-alone & 33/35 (94.3%) with chemo-SABR. Rates of severe G3-4 toxicities were 24/69 (34.8%): 2/34 (5.9%) with SABR-alone & 21/35 (60.0%) with chemo-SABR.

Conclusions: Omission of frontline chemotherapy in oligometastatic HNSCC pts led to lower severe toxicity rates, similar rates of survival & 1yOS without QoL deterioration. Medicoeconomic results will be provided.

Clinical trial identification NCT03070366. Legal entity responsible for the study GORTEC - Pr Bourhis. Funding GORTEC.

3 DCF

Christophe BORG, Véronique VENDRELY, Angélique SAINT, Thierry ANDRÉ, Pauline VAFLARD, Emmanuelle SAMALIN, Simon PERNOT, Oliver BOUCHÉ, Mustapha ZUBIR, Jérôme DESRAME, Christelle de la FOUCHARDIÈRE, Denis SMITH, François GHIRINGHELLI, Angélique VIENOT, Éric FRANÇOIS, Julien TAIEB, Karine Le MALICOT, Dewi VERNEREY, Aurélia MEURISSE, Stefano KIM.

Background: Triplet DCF (docetaxel, cisplatin and 5-fluorouracil) and doublet CP/CF (carboplatin and paclitaxel/cisplatin and 5-fluorouracil) regimens were prospectively evaluated in advanced squamous anal cell carcinoma (SCCA), and validated as standard treatments. Even though the high efficacy and good tolerance of DCF regimen were confirmed in 3 independent prospective trials, doublet CP regimen is still recommended in several guidelines based in its better safety profile with similar efficacy compared to CF regimen.

Methods: We performed a propensity score-adjusted method with inverse probability of treatment weighted (IPTW) and matched case control (MCC) comparison among patients with metastatic or non-resectable locally advanced recurrent SCCA, treated with chemotherapy as first-line regimen. The primary endpoint was the overall survival (OS), and the secondary endpoint was the progression-free survival (PFS).

Results: 247 patients were included for analysis. 154 patients received DCF and 93 patients received a doublet regimen. Patients’ characteristics and outcomes in both groups were comparable to published data. The median OS was 32.3 months with DCF and 18.3 months with doublet regimens (HR 0.53, 95%CI 0.38-0.74; p=0.0001), and the median PFS was 11.2 months with DCF versus 7.6 months with doublet regimens (HR 0.53, 95%CI 0.39-0.73; p<0.0001). The hazard ratios by IPTW and MCC analyses were 0.411 and 0.406 for OS, and 0.466 and 0.438 for PFS (Table).

Table: Multivariate Cox analyses for OS and PFS in propensity score matched population and with IPTW weighted method.

Conclusions: The triplet DCF regimen provides a high and significant benefit in OS and PFS over doublet regimens, and can be considered as upfront treatment for eligible patients with advanced SCCA.

Legal entity responsible for the study S. Kim. Funding Has not received any funding.

4 CABASTY

Presented by Pr. Stéphane OUDARD for Yohann Tran, Raffaele Ratta, Eric Voog, Philippe Barthelemy, Antoine Thiery-Vuillemin, Mostefa Bennamoun, Ali Hasbini, Kais Aldabbagh, Carolina Saldana, Emmanuel Sevin, Eric Amela, Gunhild Von Amsberg, Nadine Houede, Dominique Besson, Susan Feyerabend, Martin Boegemann, David Pfister, Martin Schostak, Olivier Huillard, Frederic Di Fiore, Amandine Quivy, Carsten Lange, Dewi Vernerey, Antoine Falcoz, Houda Belhouari, Salma Kotti, Carole Helissey

Background: In CABASTY trial (NCT02961257), CBZ 16 mg/m² q2w + G-CSF significantly reduced grade ≥3 neutropenia and/or neutropenic complications vs CBZ 25 mg/m² q3w + G-CSF with comparable overall survival (OS) benefit in older and heavily pretreated patients (pts) with mCRPC (Oudard et al. ESMO 2022). Here, we report changes in HRQL in both arms during therapy.

Methods: The Functional Assessment Cancer Therapy-Prostate (FACT-P) questionnaire was collected at each visit and analyzed in all pts exposed to CBZ with evaluable HRQL at baseline and post-baseline. Higher values indicated better HRQL. Changes of ≥10 points in FACT-P total score and ≥2 points in Prostate Cancer Subscale (PCS)-pain score, confirmed by 2 consecutive evaluations were judged clinically meaningful.

Results: 196 pts (median age, 74.6 yrs; ≥75 yrs, 49%; G8 <14, 20%; vulnerable or frail per SIOG guidelines, 30.1%; moderate to severe pain, 18%) previously treated with docetaxel and novel hormonal therapies (median 3 lines) were randomized to CBZ q3w (n=97) or q2w (n=99) + G-CSF. Median treatment duration was 19.0 and 20.1 weeks with CBZ q3w and q2w, respectively. HRQL was evaluable in 88 (90.7%) and 96 (97.0%) pts with CBZ q3w and q2w. PCS-pain improved in 35.2% vs 38.5% (CBZ q3w vs q2w). The probability of not having PCS-pain deterioration during treatment was 81.8% vs 75.0% with CBZ q3w vs q2w (HR=1.5 [95% CI, 0.80-2.9], p=0.2). Total FACT-P score improved from baseline in 17.0% vs 13.5% of pts with CBZ q3w vs q2w, respectively. FACT-P score was either stable or improved from baseline in 75.0% vs 74.0% of pts with CBZ q3w vs q2w. At 75% percentile, time to deterioration was 4.9 vs 3.3 months (HR: 1.2; p =0.57) with CBZ q3w vs q2w.

Conclusions: In this older and heavily pretreated mCRPC pts population, CBZ q3w and q2w + G-CSF similarly relieved pain and maintained or improved HRQL in 3 out of 4 pts with a comparable OS benefit. Since bi-weekly dosing induces less grade ≥3 neutropenia and/or neutropenic complications, it should be offered to pts unfit to receive the standard CBZ regimen.

Clinical trial identification NCT02961257. Legal entity responsible for the study ARTIC. Funding Sanofi.

5 ACABY PRONOBIL

Valery M, Edeline J, Henriques J, Antoun L, Héloïse Bourien, Lebeaud A, Fares N, Tournigand C, Lecomte T, Tougeron D, Hautefeuille V, Vienot A, Williet N, Bachet JB, Malka D, Smolenschi C, Hollebecque A, Walter T, Turpin A, Boilève A

Background: Biliary tract cancers (BTC) including cholangiocarcinoma (CC) and gallbladder cancer (GBC) are rare cancers with poor prognosis. Few data are available on early-onset BTC (EOBTC) defined as patients (pts) under age of 50.

Methods: A retrospective chart review was performed in pts treated for BTC in 14 French centers between 2003 and 2021. Data on demographic characteristics, therapeutic management, and molecular profile were collected. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan Meier method. Prognostic factors were assessed by univariate and multivariate analyses by Cox regression.

Results: Overall, 1256 pts with BTC were included. Patients with EOBTC (n=188, 15%) had less comorbidities according to Charlson score (63.5% vs 84.4%, p<0.0001), higher tumor stage (cT3-4: 49.9% vs 32.17%, p=0.0126), bilobar liver involvement (47.7% vs 32.1%, p=0.0002) and metastatic disease (67.5% vs 57.49%, p=0.0097) compared to older pts, but did not differ regarding primary tumor location (intrahepatic vs extrahepatic CC vs GBC), WHO performance status (PS 0-1: 94.4% vs 85.5%, p=0.15), and sex-ratio (50.8% vs 53.4% of males). First-line systemic therapy for advanced BTC (n=818, 65.2%) was mostly a doublet by GEMCIS (45.5% vs 32.1%, p=0.0091) or GEMOX (43.3% vs 56.5%, p=0.0091) in EOBTC vs non-EOBTC respectively. EOBTC pts received more frequently a 2^nd line therapy (89.5% vs 80.9%, p=0.02). For advanced BTC pts, median (m)OS was 17.0 mo vs 16.2 mo (p=0.08) and mPFS was 5.8 mo vs 6.0 mo (p=0.89), in EOBTC vs older pts respectively. Molecular profiling was performed in 72.6% of EOBTC pts vs 52.4% in older pts (p=0.0019), and less actionable alterations were found (e.g. IDH1 mutations, 7.8% vs 16.6%; p=0.029; FGFR2-fusion, 11.7% vs 8.9%; p=0.029). We did not find any usual prognostic factors in BTC (CEA, CA19-9, PS, neutrophile-lymphocyte ratio, number of extra-hepatic metastases) associated with EOBTC survival.

Conclusions: Pts with EOBTC have a more advanced disease at diagnosis, are treated more heavily at an advanced stage, and have similar PFS and OS in comparison to older BTC pts. Molecular profiling was more often performed in EOBTC pts but less actionable alterations were found.

Legal entity responsible for the study GERCOR. Funding ACABI: Association pour l'étude des cancers et affections des voies biliaires.

6 Genomic profiling of small bowel adenocarcinoma

Thomas Aparicio, Julie Henriques, Magali Svrcek, Aziz Zaanan, Sylvain Manfredi, Andrea Casadei-Gardini, David Tougeron, Jean-Marc Gornet, Denis Pezet, Eric Terrebonne, Guillaume Piessen, Pauline Afchain, Cédric Lecaille, Marc Pocard, Thierry Lecomte, Valentina Burgio, Frédéric Di Fiore, Sandrine Lavau-Denes, Stefano Cascinu, Dewi Vernerey, Pierre Laurent Puig

Background: Several genomic alterations have been described in small bowel adenocarcinoma (SBA) but the prognostic value of these alterations remains unclear. The aim of this multicentre study was to determine the genomic profile of SBA and its impact on the prognosis.

Methods: Three cohorts in France and Italy were pooled. A common dataset of genomic analysis have been performed on 35 genes of interest. MSI (MicroSatellite Instable) and MMR (MisMatch Repair) status were also assessed.

Results: A total of 188 tumour samples had conclusive results for mutation analysis. The patients (pts) were male (55.3%), with duodenum primary (58.5%), stage I-II (39.6%), III (40.6%) and IV (18.8%). with a predisposing disease (21%) mainly Lynch syndrome (LS) (n=19) and Crohn disease (CD) (n=11). The most frequent mutation were KRAS (42.0%) of which 7/79 G12C, TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). TP53 mutations were more frequent in CD (81.8%) but less frequent in LS (15.8%) than in no predisposing disease (39%). ERBB2 mutations were more frequent in LS (26.3%) than in no predisposing disease (7.5%). No APC mutation was observed in CD. KRAS and SMAD4 mutations were more frequent in tumour than in localized tumour (59.4% vs 37.7%, p=0.0164) and (24.3% vs 9.9%, p=0.0187). ERBB2 mutations were less frequent in metastatic than in localized tumour (0% vs 11.9%, p=0.0272). For localized tumour univariate analysis revealed that: age ≥65 (p=0.0327), T4 (p=0.570), high grade (p=0.0028) stage III (p=0.0390) and wild type APC (p=0.395) were associated with a poor overall survival (OS). In multivariate analysis: high grade (p=0.023), age ≥65 (p=0.0123) and wild type APC (p=0.0254) were associated with a poor OS. For metastatic tumour a trend for a better OS was observed in case of a mutated KRAS tumour (HR=0.6 (0.34-1.06), p=0.0797) in univariate analysis. dMMR/MSI status was available in 238 pts. Overall, dMMR/MSI was reported in 29.8%, 31.8% in localized and 11.3% in metastatic tumour. dMMR/MSI was associated with a better OS (HR=0.61 [0.39-0.96], p=0.0333).

Conclusions: There is different genomic profile according to the predisposing disease. MSI/dMMR predict a better prognosis. APC mutation in localized and KRAS mutation in metastatic tumour are associate with a better prognosis.

Legal entity responsible for the study the authors. Funding Fondation ARCAD, Programme Hospitalier de Recherche Clinique.

About Dewi VERNEREY

    Dewi Vernerey is a research engineer in epidemiology and biostatistics who received a master’s degree cum laude from Joseph Fourier University (Grenoble, France) with a major in engineering statistics. He defended a PhD in epidemiology and statistics in 2016. His PhD research focused on statistical methodology for risk prediction and prognostic score construction in oncology and kidney transplantation.

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