BACKGROUND:Hepatocellular carcinoma (HCC) frequently develops in underlying cirrhosis. Liver dysfunction impacts survival and may influence treatment results. About a quarter of patients with advanced HCC present with Child-Pugh B liver functions. All recent phase 3 trials validating standard of care limited inclusion to patients with Child-Pugh A liver function. Results of immunotherapy is less described in patients with altered liver function. We previously showed that the ALBI grade might be able to better select patients with Child-Pugh B liver functions who could benefit from sorafenib. Single-agent anti-PD-(L)1 antibodies might have a more favorable safety profile than standard of care combinations. METHODS:We thus launched a study, the HESTIA trial, testing tislelizumab, an anti-PD-1 antibody that was demonstrated as non-inferior to sorafenib as first-line treatment, in the population of patients with advanced HCC, Child-Pugh B and ALBI grade 1 or 2 liver function. RESULTS:In this article, we present the design of the study and first safety results. This is a single-arm phase 2 study. Fifty patients will be included. The primary endpoint is objective response rate. The first safety analysis showed no signal of increased toxicity of the drugs. However, this population is at high risk for liver-related adverse events. CONCLUSION:The study is currently pursuing accrual.

12028 Background: The relativesof cancer patients are at risk for developing emotional distress following the death of their loved one. The aim of this study was to analyze whether sending a condolence letter offering a post-mortem consultation with the referent oncologist to the relatives of patients who have died of cancer improve their long term reported outcomes, such as anxiety, depression and complicated grief. Methods: In this multicenter, prospective, randomized, academic trial, bereaved relatives, of cancer patients who died in hospital, were randomized between receiving a condolence letter (CL) suggesting post-mortem consultation versus no CL. At 3 months and 6 months after enrolment, anxiety (HAD-A), depression (HAD-D) and grief (Texas Revised Inventory of Grief [TRIG]) were assessed using self-administered questionnaires. Results: Of the 426 randomized relatives, 118 agreed to take part in the study, of whom 102 (49 CL, 53 no CL) completed the questionnaire 3 months after the relatives’ death and 92 (43 CL, 49 no CL) at 6 months. There was no differences in socio-demographic characteristics or history of depression between the two groups. Palliative care was involved for (69% CL, vs 52% non-CL) of patients, with no statistical difference between the two groups. At 3 months post enrolment, both anxiety and depression were significantly lower in the CL group than the non-CL group (mean HADS-A score 7.3 vs 9.4, p=0.026; mean HADS-D score: 5.4 vs 8.1, p=0.009). In addition, receiving a condolence letter was associated with less grief at patient’s death (past TRIG subscale: 20.7 vs 25.8, p<0.001), and less current grief (present TRIG subscale score: 45.7 vs 52.0, p=0.025). At 6 months, the HADS-D score was significantly lower in the condolence letter arm (mean score 5.7 vs 8.3, p=0.025), as was grief at patient’s death (past TRIG subscale: 21.5 vs 25.0, p=0.035). Only 5% of CL had a post mortem consultation. Conclusions: Sending a letter of condolence to relatives of cancer patients who have died in hospital may reduce subsequent grief, depression and anxiety in loved ones. Encouraging this widespread post mortem contact such as correspondence may be a non-drug alternative to reduce post-mortem depression and improve the bereavement process for relatives of cancer patients. Clinical trial information: NCT02861625 .

BackgroundBrain metastases (BM) are rare in pancreatic ductal adenocarcinoma (PDAC) and little data exists concerning these patients and their outcomes.AimWe aimed to analyze the management, practices, and outcomes of patients presenting BM from PDAC both in our institution and in all cases reported in the literature.MethodsWe conducted a retrospective, monocentric analysis using a data mining tool (ConSoRe) to identify all patients diagnosed with PDAC and BM in our comprehensive cancer center (Paoli-Calmettes Institute), from July 1997 to June 2022 (cohort 1). Simultaneously, we reviewed and pooled the case reports and case series of patients with PDAC and BM in the literature (cohort 2). The clinical characteristics of patients in each cohort were described and survival analyses were performed using the Kaplan-Meier method.ResultsIn cohort 1, 19 patients (0.3%) with PDAC and BM were identified with a median age of 69 years (range: 39-81). Most patients had metastatic disease (74%), including 21% with BM, at diagnosis. Lung metastases were present in 58% of patients. 68% of patients had neurological symptoms and 68% were treated by focal treatment (surgery: 21%, radiotherapy: 42%, Gamma Knife radiosurgery: 5%). In cohort 2, among the 61 PDAC patients with BM described in the literature, 59% had metastatic disease, including 13% with BM at diagnosis. Lung metastases were present in 36% of patient and BM treatments included: surgery (36%), radiotherapy (36%), radiosurgery (3%), or no local treatment (25%). After the pancreatic cancer diagnosis, the median time to develop BM was 7.8 months (range: 0.0-73.9) in cohort 1 and 17.0 months (range: 0.0-64.0) in cohort 2. Median overall survival (OS) in patients of cohort 1 and cohort 2 was 2.9 months (95% CI [1.7,4.0]) and 12.5 months (95% CI [7.5,17.5]), respectively.ConclusionBM are very uncommon in PDAC and seem to occur more often in younger patients with lung metastases and more indolent disease. BM are associated with poor prognosis and neurosurgery offers the best outcomes and should be considered when feasible.

e16305 Background: mFOLFIRINOX (mFFX) is a chemotherapy regimen used for gastro-intestinal (GI) cancers, in colorectal (CCR) and pancreatic cancers (PDAC) but limited by grade ≥ 3 toxicities in 50% of cases. Little data is available regarding its use in elderly patients, rarely included in phase 3 trials, although most of patients in real-life setting have median age at diagnosis > 70 y-o for both CCR and PDAC. Methods: Using the ConSore (Continuum Soins Research) software based on of medical records data mining, we identified consecutive patients > 70 y-o, treated with mFFX in Paoli-Calmettes Institute, France, from 09/2011 to 07/2022. We recorded geriatric data, adverse events (AE), and dose reduction during mFFX. We analyzed factors associated mFFX’s toxicity in elderly population with GI cancers. Results: We included 161 patients. Median age was 74 y-o [range 71-83], including 43% >75 y-o. 82% had ECOG-PS 0-1 at diagnosis. 91% had PDAC and 9% had CCR, treated for a metastatic disease in 48%. Median number of mFFX cycles was 5 [range 1-15]. G8-ONCODAGE was calculated ≤14/17 for 77%. Multidimensional geriatric assessment (MGA) was performed in 29%, but 66% without MGA had a G8 ≤14. Sarcopenia (assessed by muscle mass in L3 CT-scan) was reported in 86% and malnutrition was moderate (57%) or severe (37%). Primary dose reduction was applied to 68%, dose reduction during mFFX in 69% and 32% discontinued 1 drug during mFFX’s courses. 53% experienced a grade ≥ 3 digestive AE or unplanned hospitalization, including 3 toxic deaths. Infections (23%), diarrhea (17% G3), peripheral neuropathy (16% G3), anorexia (15% G3), thrombopenia (12% G3) and vomiting (9% G3) were the most frequent AEs.Febrile neutropenia was reported in only 4%, due to systematic use of G-CSF. Median overall survival (mOS) was 15 months (51 months for CCR, 15 months for PDAC), and was 11 months for metastatic patients and 22 months for locally advanced disease. In multivariate analysis after backward selection, factors associated with grade > II digestive toxicity and/or hospitalization were MGA for patients with G8 ≤14 (OR 0.38 [0.15; 0.92] ; p = 0.036), polypharmacy (OR 2.70 [1.07; 7.22] ; p = 0.039), psychiatric comorbidity (OR 8.38 [1.57; 75.27] , p = 0.026) and past history of another cancer (OR 0.27 [0.07; 0.92], p = 0.04). A trend was found for sarcopenia (OR 2.70 [0.79; 10.13], p = 0.12) and cardiovascular comorbidity (OR 0.43 [0.17; 1.01] p = 0.058). Conclusions: Our data reported that mFFX is toxic and associated with similar survival in a highly selected > 70y-o patients with GI cancers, compared to their youngest counterpart included in pivotal trial. However, alternative regimens/strategies should be developed to enhance efficacy and reduce AEs. Particular attention to vulnerabilities detected using G8 and managed through MGA is of importance to reduce toxicity.

PURPOSE GEMPAX was an open-label, randomized phase III clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan. METHODS Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m 2 + gemcitabine 1,000 mg/m 2 ; IV; once at day (D) 1, D8, and D15/arm A) or gemcitabine (arm B) alone once at D1, D8, and D15 every 28 days until progression, toxicity, or patient's decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety. RESULTS Overall, 211 patients (median age, 64 [30-86] years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% CI) was 6.4 (5.2 to 7.4) versus 5.9 months (4.6 to 6.9; hazard ratio [HR], 0.87 [0.63 to 1.20]; P = 0.4095), the median PFS was 3.1 (2.2 to 4.3) versus 2.0 months (1.9 to 2.3; HR, 0.64 [0.47 to 0.89]; P = 0.0067), and the ORR was 17.1% (11.3 to 24.4) versus 4.2% (0.9 to 11.9; P = 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy. CONCLUSION While GEMPAX did not meet the primary end point of OS versus gemcitabine alone in patients with mPDAC in the second-line setting, both PFS and ORR were significantly improved.

Patient satisfaction is linked to the amount of time spent with the physician. At the same time, long waiting times in hospitals are a major source of patient dissatisfaction. The aim of this study was to determine whether advance approval of outpatient chemotherapy (CT) via phone call can optimize healthcare delivery without compromising patient satisfaction with care. Between 2013 and 2016, 343 patients with breast/gynecological cancer scheduled to undergo CT on day 8 and/or day 15 of the CT cycle were enrolled in a before–after study conducted in a French comprehensive cancer center. In the control group, 168 patients received a face-to-face consultation with an oncologist on the day of CT for approval of the upcoming CT session. In the intervention group, 175 patients received a phone call from a healthcare provider the day before CT, where assessment of toxicity from the previous CT session was recorded and submitted to an oncologist for approval of the upcoming CT session. At the end of the 6th CT cycle, patient satisfaction was evaluated using EORTC IN-PATSAT32. A total of 233 questionnaires were analyzed (response rate: 77.7%). Satisfaction with care was similar between the two groups. No differences in perceived health status were observed, but self-reported time in hospital was lower in the intervention group than in the control group (p = 0.007). Advance approval of outpatient CT via phone call is feasible and particularly relevant in the current context of immunotherapy development.

TPS11568 Background: GastroIntestinal Stromal Tumors (GIST) are paradigmatic models of cancers with a driver mutation of an oncogene, in which imatinib is recommended as adjuvant therapy or treatment of locally advanced and metastatic forms. After failure of imatinib (either progression or toxicity), sunitinib and regorafenib are indicated as 2nd and 3rd lines, respectively. Beyond approved drugs, tyrosine kinase inhibitors (TKI) can bring clinical benefit because some clones remain sensitive to TKI. Lenvatinib is a broad spectrum TKI targeting KIT, RET, PDGFRA, VEGFR 1-3 and FGFR 1-4, that is approved in the treatment of differentiated thyroid carcinoma and metastatic renal cell carcinoma and hepatocellular carcinoma. Methods: This prospective, randomized, placebo-controlled, double-blinded, multicenter trial evaluates the efficacy and safety of Lenvatinib in adult GIST patients (pts) who failed at least to previous imatinib and sunitinib. Seventy-four pts will be randomly allocated in a 1:1 ratio to receive either oral lenvatinib, at a daily dose of 24mg, or its matching placebo, continuously, until progression of disease (PD) or unacceptable toxicity. Randomization will be stratified according to the number of different previous anticancer drugs (2 or > 2). The primary objective is to compare the Progression-free survival (PFS) between arms. The expected median PFS are 1.5 month in the control arm and 3.0 months in the experimental arm (HR = 0.5). Seventy one events will provide 90% power to show significant improvement in PFS, using a 2-sided log-rank test at a 10% level. Secondary endpoints include the overall survival, the objective response rate, the best overall response, the quality of life and the safety profile. Patients allocated in the placebo arm who experience PD (RECIST 1.1) may switch to active lenvatinib. Radiological endpoints will be evaluated using the RECIST 1.1. Translational objectives will be to identify blood and tumor parameters as predictive markers of lenvatinib efficacy. Recruitment has been activated in January 2020. Ten participating sites of the French Sarcoma Group will participate in the trial. Clinical trial information: NCT04193553 .

e16737 Background: Brain metastases (BM) occur extremely rare in pancreatic adenocarcinoma (PDAC) and few data are available regarding those patients‘ care and outcomes. Methods: We performed a retrospective monocentric analysis of our database to identify patients (pts) diagnosed with PDAC and BM from July 1997 to December 2019. Results: 16 pts were eligible among 4900 pts diagnosed with PDAC in our institution (0.3%). Median age was 64 years (38.2-74.6) with 50% female. At diagnosis, 68.8% were metastatic including 27.3% with synchronous BM. About 1/3 pts had ≥ 2 lines of chemotherapy before BM. BM were discovered from neurological symptoms in 62% of cases and either with systematic brain CT/MRI or unknown in 19% for both. BM treatment was: surgery (25%), whole brain radiation therapy (RT) (43.8%), stereotactic RT (6.3%), radiosurgery (6.3%), best supportive care (BSC) or unknown (6.3%). At follow-up cutoff date (01/01/2020), most of pts were dead (75%), 2 were alive and 2 lost of follow-up. Mean interval between initial diagnosis and BM was 9.9 months (mths) (0-73). Median time to develop BM was different between pts with non-metastatic or metastatic disease at diagnosis: 16.3 mths (6.5-44) and 4.2 mths (0-36.1), respectively (HR = 0.43 (CI95: 0.14-1.09; p = 0.09)). Median overall survival (mOS) was 14.5 mths (1.6-80.2). Definitely, the non-metastatic group at diagnosis had better survival with mOS of 40.2 mths (24.7-80.2) compared to 6.5 mths (1.7-49.8) for the metastatic group (HR = 0.24 (CI95: 0,06-0,63; p = 0.012)). The median survival period after diagnosis of BM was only 3.4 mths (0.5-13.7). Pts who underwent BM surgery had better survival with a median survival from surgery of 5.5 months (4-13.7) compared to RT (0.8 mths (0.4-2)) or BSC (0.6 mths (0.5-5.9)). HR for surgery versus RT was 0.12 (CI95: 0.02-0.31; p = 0.003). After BM diagnosis, 43.8% of patients had a systemic chemotherapy, without objective response on BM. One interesting metastatic pt with BRCA1 mutation achieved a complete response (CR) after FOLFIRINOX. One BM occurred 2 years after diagnosis, was treated with surgery + RT but relapsed 4.5 mths later with new BM. Extra-cranial CR was persistent. This pt, still alive, had the longest survival period after diagnosis of BM (13.7 mths) and OS (49.8 months). Conclusions: To our knowledge, this is one of the largest cohort reported of BM in PDAC. Very few cases exist to guide therapy. Surgery appears to be the best treatment for BM, when feasible. Further investigations are still needed to understand the pathogenicity of BM in pancreatic cancer.

Background: The current study aimed to evaluate the outcomes of patients with unresectable non-metastatic locally advanced pancreatic adenocarcinoma (LAPA) who did not benefit from resection considering the treatment strategy in the clinical settings. Methods: Between 2010 and 2017, a total of 234 patients underwent induction chemotherapy for LAPA that could not be treated with surgery. After oncologic restaging, continuous chemotherapy or chemoradiation (CRT) was decided for patients without metastatic disease. The Kaplan–Meier method was used to determine overall survival (OS), and the Wilcoxon test to compare survival curves. Multivariate analysis was performed using the stepwise logistic regression method. Results: FOLFIRINOX was the most common induction regimen (168 patients, 72%), with a median of 6 chemotherapy cycles and resulted in higher OS, compared to gemcitabine (19 vs. 16 months, hazard ratio (HR)=1.2, 95% confidence interval: 0.86–1.6, P =.03). However, no difference was observed after adjusting for age (≤75 years) and performance status score (0–1). At restaging, 187 patients (80%) had non-metastatic disease: CRT was administered to 126 patients (67%) while chemotherapy was continued in 61 (33%). Patients who received CRT had characteristics comparable to those who continued with chemotherapy, with similar OS. They also had longer progression-free survival (median 13.3 vs. 9.6 months, HR=1.38, 95% confidence interval: 1–1.9, P <.01) and limited short-term treatment-related toxicity. Conclusions: The median survival of patients who could not undergo surgery was 19 months. Hence, CRT should not be eliminated as a treatment option and may be useful as a part of optimised sequential chemotherapy for both local and metastatic disease.

Background and aim More than 50% of the liver should be drained in case of unresectable hilar liver stenosis; however, it remains unclear if the use of several types of drainage (endoscopic retrograde cholangiography and pancreatography, percutaneous‐biliary drainage, endoscopic ultrasound biliary drainage (EUS‐BD)), allowing better drainage, has an impact on survival. The aim of our study was to evaluate the percentage of liver drained and its correlation on survival whatever the drainage technique used. Patients and methods This study was a retrospective analysis of a prospective registry of patients with malignant drainage stenosis of the hilum. The quality of drainage was evaluated based on the percentage of liver segments drained, which was calculated by dividing the number of liver segments drained by the total number of liver segments. Drainage could be achieved via an endoscopic, EUS‐guided or percutaneous route not associated with the procedure. Results Sixty patients (38 men) were included from January 2015 to July 2016. The mean patient age was 69.84 years. Stenosis was classified as type II for 17 (29%) patients, type III for 20 (34%) patients, and type IV for 22 (37%) patients. Histology revealed cholangiocarcinoma for 26 (43%) patients, metastatic disease from colorectal cancer for 15 (25%) patients and another cancer for 19 (32%) patients. The median survival time was five (2.3–12.3) months. The percentage of liver segments drained had a significant prognostic impact on overall survival regardless of the technique used to drain the liver. The percentage of liver segments drained was dichotomized based on a threshold value of 80%, resulting in two groups (<80% and ≥80%). Univariate analysis of overall survival revealed that the patients with <80% of liver segments drained had significantly worse prognoses (hazard ratio (HR) = 3.25 (1.66–6.36), p < 0.001) than the patients with ≥80% of liver segments drained. This effect was confirmed in multivariate analysis (HR = 2.46 (1.16–5.23), p = 0.02). The other factor that affected survival was invasion of <50% of the liver by the tumor. A receiver operating characteristic curve was used to establish a correlation between patients receiving chemotherapy and the percentage of liver drained (area under the curve = 0.77 (0.65–0.88)). Conclusion The survival of patients with malignant stenosis of the biliary confluence is highly correlated with the percentage of liver segments drained, regardless of the technique used.

Breast cancer is the most frequently diagnosed cancer and the leading cause of female cancer-related death worldwide, with a median age at diagnosis between 60 and 65 years. Nevertheless, numerous studies have shown that older women are often undertreated, leading to higher rates of recurrence and mortality [ [1] Bouchardy C. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol. Oct 1 2003; 21: 3580-3587 Crossref PubMed Scopus (444) Google Scholar ]. Patients with metastatic breast cancer (MBC) pre-treated with anthracyclines and taxanes may receive capecitabine, vinorelbine, or eribulin. The latter is one of the few agents to provide a survival gain, albeit small (2.5 months) in a heavily pretreated population of MBC [ [2] Cortes J. O'Shaughnessy J. Loesch D. Blum J.L. Vahdat L.T. Petrakova K. et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. Mar 2011; 377: 914-923 Abstract Full Text Full Text PDF PubMed Scopus (871) Google Scholar ].

6588 Background: Patients’ satisfaction is known to be closely linked to the time spent with the physician. However, longer waiting times may be a source of dissatisfaction as well as organizational dysfunctions of the outpatient unit. Is a validation of chemotherapy by phone call instead of a medical consultation with a senior physician before chemotherapy (CT) is feasible without compromising patients’ satisfaction and quality of life? Methods: Pts with OMS < 1, able to respond to phone call, < 76 years, receiving day 8 and or d15 of CT were included. We enrolled 343 pts in a before/after study between 2013 and 2016. In the “before” step (control arm), 168 pts had a systematic physician consultation the same day before CT administration. In the intervention arm 175 pts received a phone call by a junior physician the day preceding CT administration. A specific questionnaire for CT -related toxicity of the previous cycle was recorded and CT was validated or not by physician. The day after, pts received prepared CT without appointment with the oncologist and delay in administration for already prepared CT. At the end of CT protocol, socio demographics, patients’ satisfaction (In-PatSat32) and health status (EQ-5D) questionnaires were completed by patients. Results: Questionnaires were completed by 83% and 74% in before and after step respectively, 241 questionnaires were analyzed. Satisfaction with care showed similar In-PatSat32 scores between arms, for satisfaction with: physician, nurse, organization and services. No differences of perceived health status and toxicity were observed between both groups, but patients’ time spent in hospital was lower in the intervention group versus the control group, (p = 0.007). Conclusions: An alternative care pathway implementing phone calls before CT administration if feasible without compromising pts’ satisfaction, quality of life and toxicity. We believe that saving time of pts, physicians and pharmacists is a way to optimize the model of care in outpatient unit, particularly in the immunotherapy area with more pts received intra venous treatment, probably for a long time.

BACKGROUNDThe present monocentric and prospective phase 1 study evaluated the safety of a metronomic chemotherapy in refractory tumors.PATIENTS AND METHODSPatients with advanced solid cancer refractory to standard therapy received a combination of low-dose vinorelbine, cyclophosphamide and interferon-alpha. A dose escalation model with 3 levels was planned. The primary end-point was safety and tolerability, secondary end-points were treatment continuation rate at 4 months, progression-free survival (PFS), overall survival (OS), radiological assessment (MRI) of anti-angiogenic effect.RESULTSThirty patients were enrolled. No dose-limiting toxicity was observed. All but two adverse events were toxicities of grade 1-2. Treatment continuation rate at 4 months was 6.67% (2 out of 30 patients). Median PFS and OS were 1.6 and 6.1 months. Exploratory MRI analyses related to anti-angiogenic effect did not show any relevant modification.CONCLUSIONThis combination of metronomic chemotherapy is well-tolerated and deserves to be deeply explored in refractory solid tumors.

BACKGROUND:Breast cancer stem cells (BCSCs) have been recognized as playing a major role in various aspects of breast cancer biology. To identify specific biomarkers of BCSCs, we have performed comparative proteomics of BCSC-enriched and mature cancer cell populations from the human breast cancer cell line (BCL), BrCA-MZ-01.METHODS:ALDEFLUOR assay was used to sort BCSC-enriched (ALDH+) and mature cancer (ALDH-) cell populations. Total proteins were extracted from both fractions and subjected to 2-Dimensional Difference In-Gel Electrophoresis (2-D DIGE). Differentially-expressed spots were excised and proteins were gel-extracted, digested and identified using MALDI-TOF MS.RESULTS:2-D DIGE identified poly(ADP-ribose) polymerase 1 (PARP1) as overexpressed in ALDH+ cells from BrCA-MZ-01. This observation was confirmed by western blot and extended to four additional human BCLs. ALDH+ cells from BRCA1-mutated HCC1937, which had the highest level of PARP1 overexpression, displayed resistance to olaparib, a specific PARP1 inhibitor.CONCLUSION:An unbiased proteomic approach identified PARP1 as upregulated in ALDH+, BCSC-enriched cells from various human BCLs, which may contribute to clinical resistance to PARP inhibitors.

Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is commonly deregulated in breast cancer and has been involved in resistance to endocrine therapy. In the BOLERO-2 study, the addition of everolimus, a selective inhibitor of mTOR protein, to exemestane was associated with a significant improvement in progression-free survival, compared to exemestane plus placebo, in patients with hormone receptor-positive, HER2-negative metastatic breast cancer, and resistant to non-steroidal aromatase inhibitor therapy. However, adverse events and treatment stops were more often observed with the combination therapy, suggesting the need for a careful benefit/risk evaluation before initiating this new combination. This review aims at synthesizing the biological basis of the everolimus-exemestane association, presenting the main validated and ongoing therapeutic trials, interests and limits, as well as the multiple potential therapeutic perspectives.

Selon le concept des cellules souches cancéreuses (CSC), la tumeur est organisée selon un modèle hiérarchique au sommet duquel on retrouve la CSC. Elle est dotée à la fois de propriétés communes aux autres cellules souches (capacité d’autorenouvellement et de différenciation) et de propriétés propres aux CSC (tumorigénicité, capacité à former des métastases, résistance aux traitements conventionnels). Les avancées récentes dans le cadre du cancer du sein ont permis de les isoler afin de mieux comprendre leurs spécificités et les cibler de manière plus efficace avec différentes thérapeutiques. Dans les essais cliniques, l’introduction de cette notion biologique ainsi que de thérapeutiques ciblant les CSC nécessite une adaptation des critères de jugement habituels et notamment du critère RECIST, basé essentiellement sur la fonte tumorale.

Background Chordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity. Case presentation We report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months. Conclusions We report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.