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Purpose: To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation. Patients and Methods: A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months. Results: Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients. Conclusions: Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

Sinonasal intestinal-type adenocarcinoma (ITAC) is a rare tumor, typically found in the ethmoid or upper nasal cavity. There is no standard systemic treatment for metastatic/locally advanced disease ineligible for upfront surgery or radiotherapy.Patients treated between 2015 and 2021 in our institution with a fluoropyrimidine plus oxaliplatin and/or irinotecan for advanced ITAC were retrospectively assessed for overall survival (OS), progression-free survival (PFS) and tumoral responses.Six patients without meningeal involvement received chemotherapy (three FOLFOX, two FOLFIRI, one FOLFIRINOX). All achieved a response, including those with brain extension. Median PFS with FOLFOX and FOLFIRI was similar (6.0 months, 95%CI 5.8-NR; 5.8 months, 95%CI 5.8-NR respectively). Three patients had meningeal involvement with meningitis symptoms and received first-line therapy. All had rapid disease progression (median PFS 1.2 months, 95%CI 1.0-NR) DISCUSSION: FOLFOX, FOLFIRI or FOLFIRINOX appear to have anti-tumor efficacy for metastatic or locally advanced unresectable ITAC, except in cases of carcinomatous meningitis. These regimens require further evaluation.

BackgroundPositron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control.Primary Objective(s)To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only.Study HypothesisSurgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer.Trial DesignThis is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment.Major Inclusion/Exclusion CriteriaMain inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT.Primary Endpoint(s)The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause.Sample Size510 eligible patientsEstimated Dates for Completing Accrual and Presenting ResultsThe estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030.Trial Registration NumberNCT05581121.

ObjectiveWe sought to evaluate the impact of chemotherapy response score according to the number of cycles of neoadjuvant chemotherapy, on disease-free survival and overall survival, in patients with advanced epithelial ovarian cancer ineligible for primary debulking surgery.MethodsThis multicenter retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV epithelial ovarian cancer who underwent 3–4 or 6 cycles of a platinum and taxane-based neoadjuvant chemotherapy, followed by complete cytoreduction surgery (CC-0) or cytoreduction to minimal residual disease (CC-1), between January 2008 and December 2015, in four institutions. Disease-free survival and overall survival were assessed according to the histological response to chemotherapy defined by the validated chemotherapy response score.ResultsA total of 365 patients were included: 219 (60.0%) received 3–4 cycles of neoadjuvant chemotherapy, and 146 (40.0%) had 6 cycles of neoadjuvant chemotherapy before cytoreductive surgery. There were no significant differences in early relapses, disease-free survival, and overall survival according to the number of neoadjuvant chemotherapy cycles. However, regardless of the number cycles of neoadjuvant chemotherapy, persistent extensive histological disease (chemotherapy response score 1–2) was significantly associated with a higher peritoneal cancer index, minimal residual disease (CC-1), and early relapses. Median disease-free survival in patients with complete or near-complete response (score 3) was 28.3 months (95% CI 21.6 to 36.8), whereas it was 16.3 months in patients with chemotherapy response score 1–2 (95% CI 14.7 to 18.0, pConclusionIn our cohort, the number of neoadjuvant chemotherapy cycles was not associated with disease-free survival or overall survival. Chemotherapy response score 3 improved oncological outcome regardless of the number of neoadjuvant chemotherapy cycles.

Waterfall plot of the RECIST response

Quality of Life scores

Purpose:To evaluate the efficacy and safety of dabrafenib-trametinib-131I for the treatment of radioactive iodine refractory metastatic differentiated thyroid cancer (DTC) with a BRAF p.V600E mutation.Patients and Methods:A prospective phase II trial including patients with RECIST progression within 18 months and no lesion > 3 cm. Following a baseline recombinant human (rh)TSH-stimulated diagnostic whole-body scan (dc1-WBS), dabrafenib and trametinib were given for 42 days. A second rhTSH-stimulated dc WBS (dc2-WBS) was done at day 28 and 131I (5.5 GBq–150 mCi after rhTSH) was administered at day 35. Primary endpoint was the 6-month RECIST objective response rate. In case of partial response (PR) at 6 or 12 months, a second treatment course could be given. Among 24 enrolled patients, 21 were evaluable at 6 months.Results:Abnormal 131I uptake was present on 5%, 65%, and 95% of the dc1-WBS, dc2-WBS, and post-therapy scans, respectively. At 6 months, PR was achieved in 38%, stable disease in 52%, and progressive disease (PD) in 10%. Ten patients received a second treatment course: one complete response and 6 PRs were observed at 6 months. The median progression-free survival (PFS) was not reached. The 12- and 24-month PFS were 82% and 68%, respectively. One death due to PD occurred at 24 months. Adverse events (AE) occurred in 96% of the patients, with 10 grade 3–4 AEs in 7 patients.Conclusions:Dabrafenib-trametinib is effective in BRAF p.V600E-mutated DTC patients for restoring 131I uptake with PR observed 6 months after 131I administration in 38% of the patients.

ObjectiveOur study aimed to evaluate the association between timing of cytoreductive surgery and pattern of presentation of the first recurrence in patients with advanced ovarian cancer. We also aimed to assess the impact of the pattern of recurrence on post-relapse overall survival according to surgical timing.MethodsThis retrospective multicenter study evaluated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer. Patients had undergone either primary debulking surgery, early interval debulking surgery after 3–4 cycles of neoadjuvant chemotherapy, or delayed debulking surgery after 6 cycles, with minimal or no residual disease, between January 2008 and December 2015. Survival analyses were conducted using the Log-rank test and the Cox model. Cumulative incidences of the different patterns of recurrence were estimated using a competing risks methodology.ResultsA total of 549 patients were included: 175 (31.9%) patients had primary, 224 (40.8%) early interval, and 150 (27.3%) delayed debulking surgery. The cumulative incidence of peritoneal recurrences at 2 years was higher with increasing neoadjuvant cycles (24.4%, 30.9% and 39.2%; p=0.019). For pleural or pulmonary recurrences, it was higher after early interval surgery (9.9%, 13.0% and 4.1%; p=0.022). Median post-relapse overall survival was 33.5 months (95% confidence interval (CI) (24.3 to 44.2)), 26.8 months (95% CI (22.8 to 32.6)), and 24.5 months (95% CI (18.6 to 29.4)) for primary, early interval, and delayed debulking surgery groups, respectively (p=0.025). The pattern of recurrence in a lymph node (hazard ratio (HR) 0.42, 95% CI (0.27 to 0.64)), delayed surgery (HR 1.53, 95% CI (1.11 to 2.13)) and time to first recurrence (HR 0.95, 95% CI (0.93 to 0.96)) were associated with post-relapse overall survival. For primary and early interval surgery, lymph node recurrences were associated with significantly longer post-relapse overall survival.ConclusionsThe pattern of first recurrence was associated with timing of surgery, with peritoneal recurrences being more frequent with the increasing number of cycles of neoadjuvant chemotherapy. Lymph node recurrences were associated with better prognosis, having higher post-relapse overall survival. This improved prognosis of lymphatic recurrences was not observed in patients who underwent delayed surgery.

Our aim was to assess the opinion of a panel of experts and obtain a consensus on the management of endometrial cancer in France and French Switzerland. A Delphi survey was carried out among a panel of French and French-speaking Swiss experts. The first questionnaire included 65 questions divided into eight categories: characterization of experts, histo-molecular characteristics and radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate–high-risk, high-risk, and metastatic cancers. The experts were asked to reply on a 9-point scale, both on the validity and the clarity of each question. After the answers were analyzed, a second questionnaire was sent to the same experts. The study took place between December 2021 and March 2022. Further, 58 (57.4%) of the 101 experts responded in the first round, and 39 recommendations were obtained (60%). Six questions were voted redundant and 20 discordant. These questions were reformulated, and, at the end of the second round, 17 recommendations were validated (85%). In total, the study presents an analysis of 56 questions and related responses. Expert advice helps to clarify non-consensual issues, standardize the management of endometrial cancer, and optimize clinical practices.

The latest European recommendations of the European Societies of Gynecological Oncology (ESGO), Radiotherapy and Oncology (ESTRO) and Anatomopathology (ESP) concerning the management of patients with endometrial cancer were published in 2021. On behalf of the French Society of Gynecologic Oncology (SFOG) and the SFOG campus, we wish to summarize for the French-speaking readership the main measures with a more specific application for France. We also incorporate data from a Delphi survey conducted with a panel of French and French-speaking Swiss experts. The data presented in this article relate to histo-molecular characteristics, radiological data of endometrial cancer, and management of low-risk, intermediate-risk, intermediate-high-risk, and metastatic cancers. The aim of this review article is to show the application of the latest international recommendations to clinicians and pathologists for the implementation of these recommendations.

The aim of our study was to assess concordance of staging laparoscopy and cytoreductive surgery (CRS) peritoneal cancer index (PCI) when applying a two-step surgical protocol. We also aimed to evaluate the accuracy of diagnostic laparoscopy to triage patients for complete cytoreduction, and to define optimal time between staging laparoscopy and CRS. We designed a retrospective review of prospectively collected data from patients with advanced ovarian cancer who underwent a diagnostic laparoscopy followed by a CRS a few weeks later (two-step surgical protocol), from January 2010 to April 2019. Only patients selected for complete cytoreduction, and with available PCI score from both surgeries were included. PCI concordance was assessed using intraclass correlation coefficient (ICC). During the study period 543 patients underwent a laparoscopic staging for ovarian carcinomatosis. Among them, 43 patients fulfilled inclusion criteria. ICC between laparoscopic and laparotomic PCI was 0.54. After applying the linear regression equation: laparoscopic PCI + 0.2 x [days between surgeries] + 2, ICC increased to 0.79. Completeness cytoreduction score and laparoscopic PCI were significantly associated (OR 1.27, 95% CI 1.03–1.57, p = 0.03). AUC of laparoscopic PCI to predict complete cytoreduction was 0.90. Concordance between laparoscopic PCI assessment and PCI score at the end of CRS is fair within a two-step surgical management. Laparoscopic assessment underestimates final PCI score by two points, and this difference increases with the delay between both surgeries. Diagnostic laparoscopy can adequately select patients for CRS, and optimal time to perform it is no more than 10 days after laparoscopy.

International audience; Background: The aim of this study was to assess current French practices in the management of patients with advanced epithelial ovarian cancer. Method: a 58-question electronic survey was distributed anonymously to the members of the SFOG (French Society of Gynaecological Oncology), GINECO-ARCAGY (National Investigators Group for Ovarian and Breast Cancer Studies in France) and FRANCOGYN (French research group in oncological and gynaecological surgery). Initial diagnostic workup and staging, pathological data, surgical data, treatments and follow-up strategies were assessed. Results: a total of 107 participants responded to emailed surveys. Most of the respondents were obstetrician-gynaecologists (37.4%), surgical oncologists (34.6%) and medical oncologists (17.8%). According to most (76.8%) participants, less than 50% of patients were eligible for primary debulking surgery (PDS). The LION study criteria were applied in 69.5% of cases during PDS and 39% after chemotherapy. The timing of BRCA testing was very heterogeneous and ranged from 1 to 6 months. The use of bevacizumab as an adjuvant schedule was lower in cases of no residual disease (for 54.5% of respondents) compared to cases of residual disease (for 63.6% of respondents). In cases of BRCA1-2 mutations, olaparib was given by 75.8–84.8% of respondents, whereas niraparib was given in cases of BRCA wild-type diseases. Conclusion: this survey provides an extensive and a unique review of current French practices in the management of patients with advanced epithelial ovarian cancer in 2021.

Procediments quirúrgics de citoreducció; Teràpia neoadjuvant; Neoplàsies d'ovari Procedimientos quirúrgicos de citorreducción; Terapia neoadyuvante; Neoplasias de ovario Cytoreduction Surgical Procedures; Neoadjuvant Therapy; Ovarian Neoplasms Objective We sought to evaluate the impact on survival of tumor burden and surgical complexity in relation to the number of cycles of neoadjuvant chemotherapy (NACT) in patients with advanced ovarian cancer (OC) with minimal (CC-1) or no residual disease (CC-0). Methods This retrospective study included patients with International Federation of Gynaecology and Obstetrics IIIC–IV stage OC who underwent debulking surgery at 4 high-volume institutions between January 2008 and December 2015. We assessed the overall survival (OS) of primary debulking surgery (PDS group), early interval debulking surgery after 3–4 cycles of NACT (early IDS group) and delayed debulking surgery after 6 cycles (DDS group) with CC-0 or CC-1 according to peritoneal cancer index (PCI) and Aletti score. Results Five hundred forty-nine women were included: 175 (31.9%) had PDS, 224 (40.8%) early IDS and 150 (27.3%) DDS. Regardless of Aletti score, median OS after PDS was significantly higher than after early IDS or DDS, but the survival difference was higher in women with an Aletti score 10, there were no differences between PDS and early IDS, but DDS was associated with decreased OS. Conclusion The benefit of complete PDS compared with NACT was maximal in patients with a low complexity score. In patients with low tumor burden, there was a survival benefit of PDS over early IDS or DDS. In women with high tumor load, DDS impaired the oncological outcome. The project that gave rise to these results received the support of a fellowship from “la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/EU18/11650038.

PURPOSE The aim of the study was to evaluate the clinical utility of pretreatment 18F-FDG PET/CT with quantitative evaluation of peritoneal metabolic cartography in relation to staging laparoscopy for ovarian carcinomatosis. PATIENTS AND METHODS A retrospective review of prospectively collected data from 84 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IIIC to IV ovarian cancer was carried out. All patients had a double-blinded 18F-FDG PET/CT review. Discriminant capacity of metabolic parameters to identify peritoneal carcinomatosis in the 13 abdominal regions according to the peritoneal cancer index was estimated with area under the receiver operating characteristic curve (AUC). RESULTS The metabolic parameter showing the best trade-off between sensitivity and specificity to predict peritoneal extension compared with peritoneal cancer index score was the metabolic tumor volume (MTV), with a Spearman ρ equal to 0.380 (P < 0.001). The AUC of MTV to diagnose peritoneal involvement in the upper abdomen (regions 1, 2, and 3) ranged from 0.740 to 0.765. MTV AUC values were lower in the small bowel regions (9-12), ranging from 0.591 to 0.681, and decreased to 0.487 in the pelvic region 6. 18F-FDG PET/CT also improved the detection of extra-abdominal disease, upstaging 35 patients (41.6%) from stage IIIC to IV compared with CT alone and leading to treatment modification in more than one third of patients. CONCLUSIONS 18F-FDG PET/CT metrics are highly accurate to reflect peritoneal tumor burden, with variable diagnostic value depending on the anatomic region. MTV is the most representative metabolic parameter to assess peritoneal tumor extension.

Commenting on a recently published article on sicca syndrome linked to immune checkpoint inhibitor therapy, this letter to the editor shares another viewpoint on the management of this immune-related adverse event.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary HLH, also known as macrophage activation syndrome, commonly presents in adulthood and characterized by acquired immune dysfunction in response to infections, malignancies, or autoinflammatory/autoimmune disorders. Secondary HLH induced by regorafenib has not been yet described. Here we report a case of HLH induced by regorafenib, confirmed by clinical, laboratory and histopathological findings, with typical results on bone marrow aspiration.

IntroductionThe objective was to evaluate whether hybrid imaging combining single photon emission tomography with computed tomography (SPECT/CT) provides additional clinical value for dectection of sentinel lymph nodes (SLNs) compared with intraoperative combined mapping in uterine and cervical malignancies.MethodsThis was a retrospective study of prospectively collected data from patients with stages IA–IB2 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018) or stage I endometrial cancer, who underwent preoperative SPECT/CT for SLN detection. All included patients had dual injection of technetium-99m (99mTc) with patent blue or indocyanine green.ResultsA total of 171 patients were included with 468 SLNs detected during surgery: 146/171 patients (85.4%) had both radiotracer and blue injection whereas 25/171 patients (14.6%) had radiotracer and indocyanine green injected. The overall detection rate was 95.3%. The detection rate of SLN mapping was 74.9% for SPECT/CT, 90.6% for99mTc, 91.8% for blue dye, and 100% for indocyanine green. Bilateral drainage was found in 140 patients (81.9%), detected by99mTc in 105 patients (61.4%), by blue in 99 patients (67.3%), by indocyanine green in 23 patients (92%), and by SPECT/CT in 62 patients (36.4%). Atypical SLN locations were identified by SPECT/CT in 64 patients (37.4%), by 99mTc in 28 patients (16.4%), by blue in 17 patients (9.9%), and by indocyanine green in 8 patients (4.7%). Sensitivity and negative predictive value of SLN biopsy to detect lymph node metastasis using dual injection of different intraoperative combined techniques were 88.9% and 97.5%, respectively.ConclusionSPECT/CT enhanced topographic delineation of SLN and more accurately identified drainage to atypical locations. Fluorescent SLN mapping using indocyanine green offered the highest SLN detection rate. When indocyanine green was used, SPECT/CT did not increase SLN detection, and did not add further information to improve lymph node localization and removal.

We compared the performance of six prognostic scores (Royal Marsden Hospital, MDACC: MD Anderson Clinical Center and MDACC + NLR: neutrophil-to-lymphocyte ratio, MD Anderson - immune checkpoint inhibitors (MDA-ICI), GRIm: Gustave Roussy Immune Score and LIPI: Lung Immune Prognostic Index) in predicting overall survival (OS) in phase I trial patients treated with immune checkpoint inhibitors (ICI). Medical records of patients with advanced solid tumors enrolled in ICI phase I trials between 2015 and 2018 at Institut Universitaire du Cancer de Toulouse-Oncopole were reviewed. The performance of prognostic scores on OS was compared using different criteria. A total of 259 patients were included. Median age was 63 years (range: 18-83). Main primary cancers were melanoma (19%), head and neck (16%), lung (13%) and bladder (10%). With a median follow-up of 15 months (95% confidence interval [CI] = [11.6;17.5]), median OS was 12.5 months (95% CI = [10.3;16.0]). All scores were associated with OS. The MDACC, LIPI and GRIm scores performed better than the others. Concordance of risk group assignment between the scoring systems was poor. According to our results, the MDACC, GRIm and LIPI scores better suited to ICI phase I settings. Adequate scoring would allow better patient selection in early ICI trials, especially during the critical period of dose escalation, and in proof-of-concept expansion cohorts.

Background Plocabulin (PM060184) is a novel marine-derived microtubule inhibitor that acts as an antitumor agent. This first-in-human study evaluated dose-limiting toxicities (DLT) to define the maximum tolerated dose (MTD) and phase II recommended dose (RD) of plocabulin given as a 10-min infusion on Day (D) 1, D8 and D15 every four weeks. Patients and methods Forty-four patients with advanced solid tumors received plocabulin following an accelerated titration design. Results Plocabulin was escalated from 1.3 mg/m2 to 14.5 mg/m2, which was defined as the MTD. No RD was confirmed, because frequent dose delays and omissions resulted in low relative dose intensity (66%) at the 12.0 mg/m2 expansion cohort. The main DLT was grade 3 peripheral sensory neuropathy (PSN); other DLTs were grade 4 tumor lysis syndrome, grade 4 cardiac failure and grade 3 myalgia. Toxicities were mainly mild to moderate, and included abdominal pain, myalgia, fatigue, nausea, and vomiting. Myelosuppression was transient and manageable. Plocabulin had a half-life of ~4 h and a wide diffusion to peripheral tissues. Antitumor response was observed in cervix carcinoma and heavily pretreated metastatic non-small cell lung cancer patients, and disease stabilization (≥3 months) in patients with colorectal, thymic, gastrointestinal stromal and breast tumors, among others. The clinical benefit rate was 33%. Conclusion The main DLT of plocabulin was PSN, as anticipated for a tubulin-binding agent. Since encouraging antitumor activity was observed, efforts to improve toxicity and to find the RD were planned in other trials evaluating D1&D8 and D1-D3 plus D15-D17 schedules.

Introduction Les anticorps anti-PD1/PDL1 representent une avancee considerable dans le traitement de nombreux cancers metastatiques. Leur utilisation peut s’associer a des toxicites d’origine immunologique desormais bien decrites, notamment dermatologiques. L’attention apportee aux manifestations orales n’a ete que limitee jusqu’ici. Nous rapportons une serie de 15 patients ayant developpe une xerostomie en cours de traitement. Materiel et methodes Observation monocentrique et retrospective d’une serie de 15 patients ayant developpe une xerostomie en cours de traitement par anti-PD1/PDL1 (seul ou en association) avec caracterisations cliniques, histologiques et immunophenotypage. Observations Quinze patients (39–78 ans) etaient adresses pour une xerostomie survenue pendant un traitement par anti-PD1/PDL1 (en monotherapie, ou en association avec un anti-CTLA4 ou une immunotherapie en cours de developpement). La mediane d’apparition de la xerostomie etait de 12 semaines. Neuf patients presentaient une xerostomie de grade 1/2 et 6 patients de grade 3. Resultats Une biopsie des glandes salivaires accessoires etait effectuee dans tous les cas et revelait une infiltration lymphocytaire ( Fig. 1 ) chez 11 patients. Le score moyen de Chisholm–Mason etait de 2. L’immunophenotypage individualisait une infiltration composee de lymphocytes T CD3+ avec predominance des lymphocytes T CD4+ ( Fig. 2 ). Un bilan immunologique etait realise dans tous les cas et les auto-anticorps (anti-SSA/Ro, anti-SSB/La, anticorps antinucleaires) etaient negatifs sauf chez un patient qui developpait un syndrome de Goujerot–Sjogren induit. Des mesures symptomatiques permettaient une amelioration moderee de la symptomatologie chez 8 patients. Deux autres etaient significativement ameliores par un court traitement de prednisolone indique pour une cytolyse hepatique de grade 3. Dans tous les cas, l’immunotherapie n’etait jamais interrompue pour la xerostomie. La symptomatologie s’ameliorait progressivement chez les patients ayant du arreter l’immunotherapie pour progression tumorale ou effet indesirable severe. Discussion La xerostomie induite par les anti-PD1/PDL1 peut apparaitre de facon isolee ou exceptionnellement dans un contexte de syndrome de Goujerot–Sjogren. Une prise en charge basee sur l’introduction de mesures symptomatiques associees eventuellement a une corticotherapie orale est proposee. L’arret de l’immunotherapie doit etre discute au cas par cas seulement en cas d’echec des mesures precedentes. Conclusion La xerostomie induite par les anti-PD1/PDL1 represente un veritable effet indesirable d’origine immunologique. Seule une evaluation prospective avec examen endobuccal systematique pourrait permettre d’en preciser l’incidence. Des etudes prospectives et comparatives sont necessaires pour evaluer l’impact d’une corticotherapie orale et ses modalites (dose, duree) dans ce contexte.

TPS6109 Background: Advanced endometrial cancer (EC) patients relapse despite treatment with combination chemotherapy and have a short progression-free survival (PFS). Data from the TGCA suggest opportunities to targeting DNA repair in women with EC. Particularly type 4 (High copy number or serous like, with frequent TP53 mutations) and type 2 (microsatellite instability hypermutated) EC can be associated with defects in double strand break DNA repair by homologous recombination (HR) and could potentially be targeted by olaparib. We propose a placebo-controlled, multicenter, two-arm, phase II trial comparing olaparib versus placebo in maintenance therapy after chemotherapy in patients with advanced/metastatic EC. Methods: The primary objective of this trial is to evaluate the efficacy of maintenance olaparib in comparison to placebo after platinum based chemotherapy, defined by PFS according to Recist. Key eligibility criteria include: advanced/metastatic histologically confirmed EC (excepted carcino-sarcoma, small cells& neuroendocrine); prior surgery, adjuvant chemotherapy, radiation and hormonal therapy are permitted; objective or stable response after first-line chemotherapy is mandatory. 147 patients are randomized (2:1) after chemotherapy to receive Olaparib 300mg twice daily or placebo in maintenance after at least 4 cycles of platinum based chemotherapy. Olaparib/placebo is continued until disease progression, unacceptable toxicity, or withdrawal. Stratification is on IHC P53 and MMR status. Primary hypothesis is a 66.7% relative increase in the median PFS rate in the olaparib arm (from 4.5 to 7.5 months), corresponding to a 0.60 Hazard Ratio. Secondary endpoints include PFS according to P53, MMR and NGS HRD status, PFS2, disease specific survival, time to subsequent therapy, overall survival, objective response, disease control rate, patient reported outcomes (assessed via EORTC QLQ-C30 and EORTC QLQ-EN24, EORTC-FA, EQ5D) and safety. Trial is recruiting in France (in February n= 40 randomization). Conclusion: this will be the first study that evaluate the efficacy of olaparib in maintenace after chemotherapy in advanced/metastastic EC, stratified on molecular profil. Clinical trial information: NCT03745950.

Background We aimed to compare the performance of 5 prognostic scores (RMH: Royal Marsden Hospital, MDACC: MD Anderson Clinical Center, MDA-ICI: MD Anderson Immune Checkpoint Inhibitors, GRIm: Gustave Roussy Immune Score and LIPI: Lung Immune Prognostic Index) in predicting overall survival (OS) in phase 1 patients treated with immune checkpoint inhibitors (ICI). Methods We reviewed records of patients with advanced solid tumors enrolled in phase 1 ICI trials between 2015 and 2018 at IUCT-O. We compared the performance of prognostic scores using Akaike criterion, discriminatory ability (Harrell’s C, the Royston’s D) and proportion of explained variation (R²) statistics. Primary endpoint was OS. ANC: Absolute Neutrophil Count ALC: Absolute Lymphocyte count (d)NLR: (Derived) Neutrophil / Lymphocyte ratio PS: Performance status Table . 493P RMH MDACC MDA-ICI GRIm LIPI Sites of metastases > 2 ✓ ✓ LDH > ULN ✓ ✓ ✓ ✓ LDH > 466 ✓ Albumin ✓ ✓ ✓ Gastrointestinal tumor ✓ PS ≥ 1 ✓ PS > 1 ✓ Age > 52 years ✓ Platelet count > 300 ✓ ANC > 4.9 ✓ ALC ✓ liver metastases ✓ NLR > 6 ✓ dNLR > 3 ✓ AIC 1310.7 1290.0 1296.4 1293.5 1296.9 CH 0.60 0.67 0.64 0.66 0.65 Dadj 0.67 0.94 0.81 0.98 0.84 R² adj 0.096 0.176 0.136 0.186 0.145 Results A total of 259 patients were included. Median age was 63 years (range 18-83). Main primary cancers were melanoma (18.5%), head and neck (16.2%), lung (12.7%) and bladder (9.7%). With a median follow up of 15 months (95% CI: [11.6;17.5]), median OS was 12.5 months (95%CI = [10.3;16.0]). All scores were associated with OS: Hazard Ratio (HR)=1.98 [1.41;2.78] for RMH score 2-3 vs 0-1, HR = 1.68 [1.09;2.60] for MDA score 2 and 3.65 [2.42;5.51] for score 3-5 vs 0-1, HR = 1.18 [0.77;1.81] for MDA-ICI score 3; HR = 2.70 [1.74;4.17] for score 4 and HR = 4.85 [2.62;8.98] for 5-6 vs 0-2, HR = 2.70 [1.92;3.79] for GRIm score 2-3 vs 0-1 and finally 1.86 [1.25;2.78] for LIPI score 1 and HR = 3.86[2.43;6.13] for score 2 vs 0. MDA and GRIm scores obtained more significant results for discrimination than RMH, MDA-ICI and LIPI (Table). Conclusions The utilization of theses scores could allow a better patients selection in early trials, especially during the critical periods of dose escalation and proof-of-concept expansion cohorts. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.