LBA5500 Background: Optimal timing of cytoreduction in non-frail patients (pts) with seemingly resectable stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma (OC) remains controversial. Methods: TRUST is an international randomized multicenter phase III trial in pts with stage IIIB-IVB OC and good performance status (ECOG 0/1) comparing primary cytoreductive surgery (PCS) followed by 6 cycles of intravenous (iv) chemotherapy to 3 cycles of neoadjuvant iv chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) and 3 further iv cycles. Maintenance treatment with bevacizumab and/or PARP inhibitors was allowed if selection criteria was similar for both arms. Pts were eligible for the study if preoperative clinical and radiologic assessment identified them as potential candidates for PCS. To ensure surgical quality, participating centers complied with an onsite surgery quality assurance audit, had adequate infrastructure, surgical proficiency (complete resection rates ≥50% in PCS) and sufficient volume (≥36 PCS/year). The intent to treat analysis population included all eligible pts with confirmed stage IIIB-IVB disease. The primary endpoint was overall survival (OS). Superiority was tested using a two-sided stratified log-rank test with significance level 0.05. Secondary endpoints were progression-free survival (PFS) and surgical complications. Results: A total of 688 eligible pts (median age: 63y; range: 32-83) underwent randomization: 345 were assigned to PCS and 343 to NACT/ICS. 91% had high-grade serous histology. Complete resection was achieved in 61.7%/62.9% of all randomized/all operated pts in the PCS group and 72%/76.6% in the ICS group. Median PFS was 22.2 months in the PCS group, and 19.7 months in the ICS group (HR 0.80 95%CI: 0.66-0.96; p=0.02). Median OS was 54.3 months in the PCS group and 48.3 months in the ICS group (HR 0.89 95%CI: 0.74-1.08; p=0.24). Pts with complete cytoreduction after PCS had the most favorable outcome, with a median PFS and OS of 27.9 and 67.0 months, respectively. A long-term benefit from PCS was seen in all analyzed subgroups. The benefit of PCS was most prominent in stage III pts (n=468): median PFS for PCS vs ICS, 26.3 vs 21.4 mos; median OS for PCS vs ICS, 63.7 vs 53.2 months. Major postoperative complication rates were acceptable, with a 30-day postoperative mortality rate of < 1% in both groups. Conclusions: In expert centers with proven surgical quality, PCS followed by iv chemotherapy resulted in a significantly longer median PFS and a numerically longer OS compared to NACT/ICS in non-frail OC pts. Although statistical significance in the primary endpoint was not reached, this is the first randomized trial to show a benefit of PCS over ICS. This benefit is likely to be associated with the high complete resection rate, reinforcing PCS as a standard of care in non-frail pts with seemingly resectable advanced OC. Clinical trial information: NCT02828618 .
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.).
Track how often percutaneous endoscopic gastrostomy (PEG) tubes are used in German geriatric inpatient care (2006–2024), associated nutritionally relevant diagnoses and in-hospital mortality. Among 1,355,436 admissions (≥ 60 y; mean 83 y; 67
Objective Dostarlimab+carboplatin-paclitaxel followed by dostarlimab maintenance demonstrated statistically significant and clinically meaningful benefits in progression-free and overall survival in the overall population of primary advanced/recurrent endometrial cancer versus chemotherapy alone in Part 1 of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796). Part 2 evaluated the efficacy and safety of the addition of the poly(adenosine diphosphate-ribose) polymerase inhibitor niraparib to dostarlimab maintenance following dostarlimab+chemotherapy versus placebo maintenance following placebo+chemotherapy in primary advanced/recurrent endometrial cancer. Methods Patients were randomized 2:1 to dostarlimab+chemotherapy followed by niraparib+dostarlimab maintenance (niraparib+dostarlimab arm) or placebo+chemotherapy followed by placebo maintenance (control arm). Primary endpoint was progression-free survival in the overall and mismatch repair-proficient/micro-satellite stable populations. Overall survival (key secondary endpoint) and safety were assessed. Results In total, 291 patients were randomized (192 to niraparib+dostarlimab; 99 to control). With approximately 22 months of follow-up, the risk of progression or death was significantly reduced by 40% (hazard ratio 0.60, 95% confidence interval 0.43 to 0.82, p <.001) and 37% (hazard ratio 0.63, 95% confidence interval 0.44 to 0.91, p =.006) with niraparib+dostarlimab versus the control in the overall and mismatch repair-proficient/micro-satellite stable populations, respectively. At 36.2 months of follow-up, no overall survival benefit was observed with niraparib+dostarlimab versus the control (hazard ratio 1.2, 95% confidence interval 0.81 to 1.78).Grade ≥3 treatment-related adverse events occurred in 70.7% of patients in the niraparib+dostarlimab arm and 37.5% in the control arm; serious treatment-related adverse events occurred in 24.6% and 9.4%, respectively. Discontinuations due to adverse events occurred in 38.7% of patients in the niraparib+dostarlimab arm and 11.5% in the control arm. Conclusions While the addition of niraparib to dostarlimab maintenance showed a significant improvement in progression-free survival, there was no observed overall survival benefit. Dostarlimab+carboplatin-paclitaxel followed by dostarlimab maintenance remains the only regimen to demonstrate significant overall survival benefit versus carboplatin-paclitaxel alone in primary advanced/recurrent endometrial cancer.
Somatostatin receptor (SSTR)-targeting radiotracers hold promise for theranostic applications in breast cancer (BC). This retrospective single-center study aimed to assess the proportion of SSTR-positive BC and its relevance for peptide receptor radionuclide therapy. SSTR-agonist- and SSTR-antagonist-based PET tracers are compared. Methods: Patients with BC who underwent PET imaging with SSTR agonist [68Ga]Ga-DOTATOC or SSTR antagonist [68Ga]Ga-SSO120 (February 2023 to February 2025) for initial or follow-up staging were included. All patients underwent [18F]FDG PET, which was used as the reference standard. Mean administered activities and uptake times were 88 MBq for 64 min with [68Ga]Ga-DOTATOC and 131 MBq for 66 min with [68Ga]Ga-SSO120, respectively. PET-positive lesions were reported in 6 anatomic categories. Tumors were segmented; SUVs, tumor-to-liver ratios, and tumor volumes were calculated. Time to progression stratified by SSTR expression was assessed using the log-rank test. Results: In total, 37 patients with BC (26 estrogen-receptor [ER]-positive, 11 triple negative [TN]) were identified; final analysis was limited to 30 patients after excluding 7 with no detectable tumor. Most had metastatic disease (M1) at staging (26/36). On the patient level, SSTR-positive tumor (≥1 lesion) was detected in 80% of ER-positive BC (16/20) and in 50% of patients with TNBC (5/10). In ER-positive disease, positivity was comparable for [68Ga]Ga-DOTATOC (85%) and [68Ga]Ga-SSO120 (71%), whereas in TNBC, positivity was observed with [68Ga]Ga-DOTATOC (83%) only. On the region level, 60% (31/52) of [18F]FDG-positive regions in ER-positive BC and 33% (7/21) in TNBC were SSTR-positive. Region-based mean SUVmax was generally lower with SSTR imaging: 7.2 ± 3.4 versus 9.3 ± 4.3 ([68Ga]Ga-DOTATOC vs. [18F]FDG) and 4.5 ± 1.4 versus 8.1 ± 3.2 ([68Ga]Ga-SSO120 vs. [18F]FDG) in ER-positive BC and 4.1 ± 0.6 versus 19.8 ± 3.3 ([68Ga]Ga-DOTATOC vs. [18F]FDG), with absent [68Ga]Ga-SSO120 uptake in patients with TNBC. One patient reached a Krenning score of 3, indicating technical eligibility for peptide receptor radionuclide therapy. SSTR positivity did not correlate with time to progression. Conclusion: SSTR may serve as a promising radiotheranostic target in a small subset of patients with advanced metastatic ER-positive BC. Tumor uptake was mostly moderate, without substantial difference between [68Ga]Ga-DOTATOC and [68Ga]Ga-SSO120. For imaging, [18F]FDG PET outperformed [68Ga]Ga-SSTR PET in patients with ER-positive BC and TNBC.
