Gustave Roussy is the first leader cancer-research hospital in Europe and ranked among the top 5 best specialized hospitals in the world . It is a centre for high quality patient care, research and teaching. It is highly-known for the treatment of (among others): skin cancers like melanoma, breast cancer, and lung cancer. It provides access to care with many expert doctors who have historically revolutionized the treatment of cancer and contributed to the surge of new molecules in the treatment of cancers and tumors. It is located in the Parisian area. It is named after Gustave Roussy, a Swiss-French neuropathologist.In April 2019, three new interventional radiology rooms were inaugurated, making it the largest platform of this type in Europe, entirely dedicated to oncology. Interventional radiology is a so-called "minimally invasive" diagnostic and treatment technique, which uses images to guide access to deep-lying organs, without having to "open up" patients. Gustave Roussy carries out more than 4,000 operations of this type each year.
BACKGROUND:PORTEC-4a investigated molecular risk profile-based individualised adjuvant treatment for women with high-intermediate risk endometrial cancer, aiming to reduce both overtreatment and undertreatment while optimising locoregional control. METHODS:PORTEC-4a was a randomised, open-label, phase 3, multicentre, non-inferiority trial, conducted across eight European countries. Women (aged ≥18 years and with a WHO performance score of 0-2) with early stage high-intermediate risk endometrial cancer were eligible. Patients were randomly assigned post-surgery in a 2:1 ratio to either adjuvant treatment according to their molecular integrated risk profile or to standard vaginal brachytherapy. Allocation used a biased-coin minimisation with stratification for participating centre, grade, and lymphadenectomy. Adjuvant treatment in the molecular-profile group in case of favourable profile (POLE-mutated or no specific molecular profile [NSMP]-CTNNB1 wildtype) was observation, for intermediate profile (mismatch repair deficient or NSMP-CTNNB1 mutated) was brachytherapy (21 Gy in three fractions of 7 Gy given at 5 to 7 day intervals), and for unfavourable profile (p53 abnormal or substantial lymphovascular space invasion or L1 cell adhesion molecule overexpression) was pelvic radiotherapy (45·0-48·6 Gy in 1·8-2·0 Gy fractions, 5 days per week). The primary endpoint was overall 5-year cumulative incidence of vaginal recurrence as first event. Kaplan-Meier, Cox model, and cumulative incidence with competing risks were used for final analysis in the intention-to-treat population. Patient advocates were involved during grant application and trial conduct. The trial is registered with the Netherlands Trial Registry (NTR5841), the ISRCTN registry (ISRCTN11659025), and ClinicalTrials.gov (NCT03469674), and follow-up is ongoing. FINDINGS:Between June 1, 2016, and Dec 24, 2021, 569 patients were enrolled in PORTEC-4a. After the addition of 23 favourable patients out of PORTEC-4, the final combined PORTEC-4a cohort consisted of 564 eligible and evaluable patients (367 in the molecular profile group and 197 in the standard group). All patients were female, the median age was 69·0 years (IQR 63·0-73·5), and data on race and ethnicity were not collected. Median follow-up was 58·1 months (IQR 40·7-63·6). In the molecular profile group 168 (46%) patients had a favourable profile, 148 (40%) had an intermediate profile, and 51 (14%) had an unfavourable profile. The 5-year cumulative incidence of vaginal recurrence was 4·5% (95% CI 2·23-6·76) in the molecular profile group and 1·6% (0·00-3·32) in the standard group (HR 2·71 [95% CI 0·79-9·34]). The upper-bound of the one-sided confidence interval of the difference (5·3%) was below the predefined-equivalence margin of 7·0% (pnon-inferiority=0·005). The second primary analysis in patients with a favourable molecular profile showed 5-year vaginal recurrence of 4·1% (95% CI 0·81-7·37) in the molecular profile group versus 0·9% (0·00-2·78) in the standard group (HR 3·97 [95% CI 0·48-32·95]). Adverse events were mainly grades 1-2, with grade 3 or above related genitourinary toxicities in four (1%) of 367 versus four (2%) of 197, without substantial differences between groups. Five serious adverse events occurred, of which one was possibly related to treatment (vaginal scar dehiscence). No treatment-related deaths occurred. INTERPRETATION:Individualised adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high-intermediate risk endometrial cancer; it spared 46% of patients with a favourable profile from adjuvant treatment, and reduces both overtreatment and undertreatment. FUNDING:KWF Dutch Cancer Society.
BACKGROUND:Dual anti-human epidermal growth factor receptor 2 (HER2) therapy plus chemotherapy followed by maintenance treatment with HER2-targeted and endocrine therapies is standard first-line treatment for hormone-receptor-positive, HER2-positive metastatic breast cancer. On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies. METHODS:In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib. The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival. RESULTS:A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy. At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survival than those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02). Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group. CONCLUSIONS:The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survival over standard therapy, with increased toxic effects, mainly neutropenia. (Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).
Dysregulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway has been implicated in oncogenesis, treatment resistance, and disease progression, making it an attractive target for anticancer drug development. Early experiences with PI3K/AKT/mTOR inhibitors have highlighted challenges associated with their modest efficacy, as well as safety and tolerability issues; however, several effective next-generation PI3K/AKT/mTOR inhibitors have now been approved for patients with breast cancer. As a result, there is a growing need to understand the presentation, characteristics, and management of common toxicities (hyperglycemia, rash, stomatitis, and diarrhea). This review summarizes available safety data from phase III randomized clinical trials for approved PI3K/AKT/mTOR pathway-targeted therapies (everolimus, alpelisib, capivasertib, and inavolisib), including incidence, severity, adverse event-related dose modifications, and time to onset. We also provide guidance for preparation, monitoring, and management strategies for integrating these therapies into clinical practice, with the hope that appropriate support will allow patients to tolerate higher PI3K/AKT/mTOR inhibitor dose intensities, which has the potential to translate to improved patient outcomes.
This multisociety, multidisciplinary consensus—formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology—was developed to standardise the assessment of ablation margins in liver tumour thermal ablation. A modified Delphi process, consisting of two online surveys and a hybrid (online and in-person meeting in Innsbruk) consensus meeting of 72 experts from North America, South America, Europe, and Asia. Formal consensus was reached for 150 (75%) of 199 statements. Strong agreement was observed between interventional and surgical oncologists, with only 12 (6%) of 199 statements showing significantly different ratings. Participants agreed that ablation margins should be assessed and documented for every treated tumour. Margins should be assessed quantitatively in three dimensions, with contrast-enhanced CT or MRI, preferably intraprocedurally with ablation confirmation software. Ablation margins should be categorised as A0 (tumour completely covered with sufficient margin), A1 (tumour completely covered but insufficient margin), or A2 (portion of tumour remains unablated). This effort is, to our knowledge, the first international consensus initiative to define best-practice recommendations for margin assessment in liver tumour thermal ablation to standardise practices, aiming to improve and promote uniform outcomes.
BACKGROUND:Chemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT. METHODS:We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers. Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles. The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles. RESULTS:Of the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease. The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval [CI], 4.44 to 23.72; P<0.001) and a risk ratio of 2.77 (95% CI, 1.78 to 4.30; P<0.001). Adverse events of grade 3 or higher occurred in 37% of the patients who received romiplostim and in 22% of those who received placebo, which primarily reflected chemotherapy effects. Adverse events that were considered by the investigator to be related to romiplostim or placebo occurred in 12% of patients who received romiplostim and in 7% who received placebo, with the most frequent being nausea (2% in each group) and headache (2% in the romiplostim group); none were serious or led to death or discontinuation of romiplostim, placebo, or chemotherapy. Thromboembolic events occurred in 2% of patients who received romiplostim and in no patients who received placebo. CONCLUSIONS:In this phase 3, placebo-controlled trial, romiplostim was efficacious in treating CIT. (Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.).
