Institut Jules Bordet

LBA109 Background: Although PD-1/PD-L1 inhibitors plus chemo have expanded treatment options for previously untreated PD-L1–positive advanced TNBC, there still remains a critical unmet need to improve outcomes. SG previously demonstrated significant clinical benefit in pretreated metastatic TNBC (mTNBC). We report results from the ASCENT-04/KEYNOTE-D19 study in patients with previously untreated, PD-L1–positive (CPS ≥ 10; 22C3 assay) locally advanced unresectable or mTNBC. Methods: Patients were randomized 1:1 to SG (10 mg/kg IV, day 1 & 8) + pembro (200 mg, day 1, max 35 cycles) in 21-day cycles or chemo (gemcitabine + carboplatin, paclitaxel, nab-paclitaxel) + pembro until disease progression or unacceptable toxicity. Randomization was stratified by curative treatment-free interval, geography, and prior exposure to anti–PD-(L)1 therapy in the curative setting. Primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Key secondary endpoints include overall survival (OS); objective response rate (ORR) and duration of response (DOR) by BICR; and safety. Results: 443 patients were randomized at a 1:1 ratio: 221 to SG + pembro and 222 to chemo + pembro. The median follow-up was 14 mo. SG + pembro showed a significant improvement in PFS by BICR compared with chemo + pembro (hazard ratio [HR], 0.65; 95% CI, 0.51-0.84; P = .0009; Table). Median DOR was 16.5 mo for SG + pembro vs 9.2 mo for chemo + pembro (Table). Although OS data were immature, a positive early trend in OS improvement was also noted. The most frequent (≥ 10% of patients) grade ≥ 3 treatment-emergent adverse events (TEAEs) with SG + pembro were neutropenia (43%) and diarrhea (10%); and with chemo + pembro were neutropenia (45%), anemia (16%), and thrombocytopenia (14%). Conclusions: SG + pembro led to a statistically significant and clinically meaningful improvement in PFS vs chemo + pembro with durable responses, no new safety concerns for SG or pembro, and a lower rate of treatment discontinuation due to TEAEs in patients with previously untreated, PD-L1–positive advanced TNBC. These data support the use of SG + pembro as a potential new standard of care treatment in this patient population. Clinical trial information: NCT05382286 . Efficacy, BICR, intent-to-treat SG + pembro(n = 221) Chemo + pembro(n = 222) Median PFS (95% CI), mo 11.2 (9.3-16.7) 7.8 (7.3-9.3) HR (95% CI); P -value (adjusted for randomization stratification factors) 0.65 (0.51-0.84); P = .0009 ORR (95% CI), % 59.7 (52.9-66.3) 53.2 (46.4-59.9) Median DOR (95% CI), mo 16.5 (12.7-19.5) 9.2 (7.6-11.3) Safety (TEAEs), all treated, n (%) n = 221 n = 220 Any grade; grade ≥ 3 220 (> 99); 158 (71) 219 (> 99); 154 (70) Led to dose reduction 78 (35) 96 (44) Led to any treatment discontinuation 26 (12) 68 (31)

Thoracic outlet syndrome (TOS) refers to a group of conditions caused by extrinsic compression of neurovascular structures at the thoracic outlet. Arterial TOS (aTOS) is the rarest form and may present with upper limb ischemic symptoms such as pain, coldness, pallor, and numbness, most often due to bony abnormalities such as a cervical rib.  We report the case of a 19-year-old woman on combined oral contraceptive therapy who presented with acute ischemia of the right upper limb. Duplex ultrasound and computed tomography angiography revealed thrombosis of the right subclavian artery in the setting of a right cervical rib. The patient underwent urgent thrombectomy followed by definitive decompression through supraclavicular resection of the supernumerary rib.  This case illustrates a rare presentation of aTOS in a young patient and highlights the importance of prompt recognition and appropriate surgical management.

Abstract Purpose: In RET-rearranged non–small cell lung cancer (NSCLC), treatment options after first-generation selective RET inhibitors (SRI) are limited, and the value of SRI retreatment remains unclear. This study evaluates outcomes of SRI retreatment. Experimental Design: This multicenter retrospective study included patients with advanced RET-rearranged NSCLC who received ≥2 SRI-based therapy lines. Of 411 SRI-treated patients, 41 (10%) underwent SRI retreatment. Outcomes included objective response rate (ORR), progression-free survival (PFS), 6-month PFS, time to treatment failure, adverse events (AE). Results: Among 41 patients, 14 (34%) discontinued the initial SRI because of toxicity and 27 (66%) because of progression. After discontinuation for toxicity, all switched to an alternate SRI, achieving an ORR of 67%, median PFS of 9.9 months, and 6-month PFS of 80.3%. AEs reoccurred in nine patients (64%), with grade ≥3 AEs in 3 (21%) who switched at full dose. Among patients who discontinued because of progression, SRI monotherapy (n = 13) achieved an ORR of 23%, median PFS of 7 months, and 6-month PFS of 61.5%. Benefit was observed in patients with brain-only or oligoprogressive disease or dose reduction on first SRI. Combination therapy (n = 14; targeted agents, n = 11; chemotherapy, n = 3) achieved an ORR of 39%, median PFS of 4 months, and 6-month PFS of 27.3%. Conclusions: Same-class SRI switch after toxicity is feasible and clinically active but warrants cautious, dose-adjusted switching to mitigate toxicities. The efficacy of SRI rechallenge after progression seems limited overall. However, selected patients, such as those with brain-only or oligoprogressive disease, may derive benefit.

TPS619 Background: Adjuvant ET is the standard of care (SOC) for treating ER+/HER2- eBC. Despite advances to optimize adjuvant treatment in high-risk ER+/HER2- eBC, there continues to be a risk of local and metastatic (incurable) recurrence that persists, and new therapies with desirable safety profiles are warranted. Elacestrant is a next-generation oral SERD that provides a novel mechanism of action that has shown both SERD (degradative) and SERM (partial agonist) activity that differs from currently available adjuvant ET (Wardell, ERC 2015). In the EMERALD trial, elacestrant significantly prolonged PFS vs SOC ET in the overall population (HR 0.70; 95% CI 0.55-0.88; P=0.0018) and in patients with ESR1 -mut tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) (Bidard, JCO 2022). In patients with ESR1 -mut tumors who received prior ET+CDK4/6i ≥12 mo, mPFS with elacestrant was 8.6 vs 1.9 mo with SOC ET (Bardia, CCR 2024). In a preoperative, window of opportunity ER+/HER2- eBC trial (SOLTI-1905-ELIPSE), elacestrant was associated with complete cell cycle arrest (defined as Ki67<2.7%) rate of 27% and a statistically significant mean change from baseline, shifting tumor biology toward a more endocrine-sensitive and less proliferative tumor phenotype (Vidal, CCR 2025). Given that elacestrant demonstrated efficacy in mBC regardless of ESR1 -mut status relative to SOC ET and has shown biologic activity in eBC, it is hypothesized that elacestrant can prolong invasive breast cancer-free survival (IBCFS) in patients with high-risk eBC who received prior adjuvant ET±CDK4/6i. Methods: ELEGANT (NCT06492616) is a global, multicenter, open-label phase 3 study designed to evaluate elacestrant vs SOC ET (AI or tamoxifen) in patients with eBC and a high risk of recurrence. Patients will be randomized 1:1 to continue SOC ET or to elacestrant for a duration of 5 yrs. Eligible patients are women or men with ER+/HER2− node-positive eBC who have completed 24-60 mo of adjuvant ET±CDK4/6i and have ECOG PS ≤1. Patients who received a prior CDK4/6i or a PARP inhibitor must have already completed or discontinued these treatments. Pre/perimenopausal women and men will be administered a LHRH agonist. Exclusion criteria include inflammatory breast cancer, history of prior invasive breast cancer, and >6 mo continuous interruption of prior SOC adjuvant ET or discontinuation of adjuvant ET >6 mo prior to randomization. The primary endpoint is IBCFS. Key secondary endpoints include distant relapse-free survival, overall survival, invasive disease-free survival, safety, patient-reported outcomes-quality of life, and pharmacokinetics. Status: Planned enrollment is 4,220 patients; recruitment is ongoing. Clinical trial information: NCT06492616 .

Aims:Surgical management of intermediate and malignant tumours in the pelvis is complex. Complications are frequent and either related to the surgery itself or to post-surgical failure of the reconstruction technique. This systematic review and meta-analysis aims at analyzing all reported complications following PI to PIII pelvic resections for intermediate and malignant tumours. Methods:Based on a systematic literature search on PubMed adhering to the PRISMA guidelines, 1,683 study records were identified, of which we included 90 original studies published until 22 July 2025. Overall complication rates were assessed with random-effects meta-analysis. Differences in complication rates between reconstruction types (i.e. megaprosthetic, mostly biological, none) were evaluated with meta regression analysis. Results:Data on 2,199 patients (1,250 males (57%)) with mainly PI to PIII pelvic resections were analyzed. The most common reconstruction types were custom-made implants (21%; n = 451) and ice-cream cone prostheses (14%; n = 312). Pooled rates of infections, wound healing problems, nerve injuries, and deep vein thrombosis (DVT) amounted to 15% (95% CI 12% to 18%), 13% (95% CI 10% to 15%), 7% (95% CI 5% to 9%), and 4% (95% CI 2% to 6%), respectively. Further, pooled implant revision/removal and secondary external hemipelvectomy rates were 14% (95% CI 11% to 17%) and 4% (95% CI 3% to 5%). Mostly biological reconstructions were associated with higher rates of nerve injuries (p < 0.001), construct failures (p = 0.010), and secondary implant revision/removal (p = 0.003) compared to megaprosthetic reconstruction. Further, biological reconstructions were associated with increased secondary external hemipelvectomy rates compared to megaprosthetic reconstructions (p = 0.005) or no reconstructions (p = 0.001). Conclusion:Treatment of pelvic malignancies is challenging, with technically demanding resections and complex reconstructions. Across all reconstruction techniques following sacrum-sparing pelvic resections, infections and wound healing problems are the most common complications, yet there is also a considerable proportion of patients with neurovascular complications and DVTs.