The KEYNOTE-522 trial demonstrated the benefit of adding pembrolizumab to neoadjuvant chemotherapy in patients with stage II-III triple-negative breast cancer (TNBC), showing improvements in both pathological complete response (pCR) rates and overall survival. However, a key limitation of the KEYNOTE-522 trial is that it did not incorporate the use of post-neoadjuvant capecitabine for patients who did not achieve a pCR, despite evidence that capecitabine improves survival in this population. Although post-neoadjuvant capecitabine combined with pembrolizumab is commonly discussed, there is no prospective data confirming its efficacy and tolerance in clinical practice. CAPPA (NCT0597386) is a phase II, open-label, multicenter trial evaluating the addition of capecitabine to pembrolizumab as adjuvant therapy in patients with stage II-IIIb TNBC and residual disease after neoadjuvant chemo-immunotherapy. Main inclusion criteria are: (i) Histologically confirmed TNBC, defined as HER2-negative (according to ASCO/CAP criteria) and <10% of cells staining positive for ER and PR by IHC; (ii) Patients who received standard neoadjuvant chemo-immunotherapy (minimum of 6 cycles); (iii) Absence of pCR, defined as RCB class I-III. This trial includes two distinct cohorts: (i) A prospective experimental cohort (N=220), patients will receive capecitabine (1000 mg/m2 BID, 14 days on and 7 days off) combined with pembrolizumab (200 mg every 3 weeks) for 6 months. Capecitabine is reduced at a dose of 825 mg/m2 BID during radiotherapy, performed as per standard practice, if indicated. (ii) An external cohort (N = 220), reflecting the treatment received in the KN-522 trial, will be enrolled in an ambispective manner and will include patients treated with pembrolizumab as part of standard adjuvant treatment, with similar eligibility criteria. The primary endpoint is the 2-year invasive disease-free survival (iDFS) rate. Secondary endpoints include distant disease-free survival (DDFS), overall survival (OS), and safety. Ancillary studies will be conducted on tumor biopsies, surgical specimens, and blood samples. The first patient was enrolled in March 2025. As of July 9, N=14 and 17 pts have been included in the experimental and external cohort, respectively. The inclusion period is expected to last 18 months. PHRC-K (grant PHRC-K22-084); Women’s Cancer Institute of Institut Curie (grant ANR-23-IAHU-0006). D. Loirat, F. C. Bidard, J. Grenier, T. L’Haridon, A. Kieffer, F. Dalenc, C. Goislard De Monsabert, F. Ricci, M. By, D. Bello Roufai, Y. Kirova, T. Roque, A. Savignoni, J. Y. Pierga. Cappa, a phase 2 study to evaluate capecitabine plus pembrolizumab as post-operative adjuvant therapy for triple-negative breast cancer with residual disease after neoadjuvant chemo-immunotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-07-16.
BACKGROUND:Despite constant developments in radiotherapy, optimizing Volumetric Modulated Arc Therapy (VMAT) dose distributions for whole breast with extensive lymph node involvement remains a challenge. The aim of this study was to gain insights into clinical practices and to identify effective planning strategies. METHODS:The participants of the European Federation of Organisations for Medical Physics VMAT Breast Working Group answered a survey regarding treatment planning routines for breast cancer irradiation and generated a treatment plan for a challenging patient case. The dose prescription was 50.4 Gy in 28 fractions for breast and lymph node volumes, and a simultaneous integrated boost (SIB) of 63 Gy. RESULTS:The survey was completed by 25 participants and covered a wide spectrum of topics of VMAT treatment planning, including beam geometry and organs at risk (OAR) dose constraints. In addition, 22 plans were submitted for comparison. The mean doses ranged between: PTV breast 51.9---54.1 Gy, PTV lymph nodes 49.7---52.1 Gy, SIB 61.5---66.5 Gy, heart 1.5---9.5 Gy, ipsilateral lung 12.0---17.3 Gy, contralateral lung 1.2---6.5 Gy and contralateral breast 1.6---8.9 Gy. Five treatment planning strategies, with high target coverage and the lowest doses to organs at risk, are presented. CONCLUSION:There is a wide variation in VMAT breast planning approaches, planning goals and prioritisation of PTVs and OARs across institutions. Descriptions of effective planning strategies for a challenging breast case are presented.
The use of docetaxel in the (neo)adjuvant treatment of early-stage breast cancer (eBC) is frequently linked to notable nail toxicities, which can negatively impact quality of life (QoL) and potentially lead to treatment delays. Cryotherapy, involving the use of frozen gloves and socks, is used as a strategy to decrease docetaxel-induced nail toxicity. Strong evidence supporting its efficacy at lower cumulative doses of docetaxel and its overall tolerability remains limited. BANQUISE trial was a randomized, open-label, multicenter study investigating the efficacy of cryotherapy in eBC patients receiving three cycles of (neo)adjuvant docetaxel (100 mg/m2) following three cycles of (F)EC 100. Participants were randomized after completing three cycles of (F)EC to either the cryotherapy group, with frozen gloves and socks applied 15 minutes before and removed 15 minutes after the docetaxel infusion, or to the control group. The primary endpoint was the incidence of nail toxicity grade ≥ 2 between the first dose of docetaxel and eight weeks after the last dose of docetaxel, assessed using CTCAE v4.0 criteria by investigators. Secondary endpoints included a docetaxel nail toxicity (DNT) score assessed by a blinded dermatologist at weeks 8 and 24 using photographs. This score integrates the CTCAE V4.0 grade and the number of affected fingers, assigning 1 point per digit for grade 1 toxicity and 5 points per digit for grade 2 toxicity. Cryotherapy tolerability, and patient-reported outcomes (PROs) were measured at each cycle and week 8 and 24 after last dose of docetaxel by the EORTC QLQ-C30 and BR23 questionnaires. Statistical analyses used chi-squared and t-tests, with significance set at p<0.05. From January 2014 to March 2019, a total of 280 patients were randomized to either the cryotherapy arm (n=141) or the control arm (n=139). The median age was 54 years (range 27-78). The mean cumulative dose of docetaxel was 471 mg (range: 150-660 mg) in the cryotherapy arm and 467 mg (range: 176-600 mg) in the control arm. Docetaxel dose reduction was required in 28 patients (21.9%) in the cryotherapy group and 30 patients (24.6%) in the control group. Frozen gloves were worn by 119 patients (84%) during all three courses of docetaxel, by 126 patients (89%) during two courses, and by 139 patients (99%) during one course. In the intention-to-treat population, cryotherapy significantly reduced the incidence of grade ≥ 2 nail toxicity at week 8 after the final docetaxel dose (18% vs. 37%, p < 0.001), as assessed by the investigators. This decrease was observed in both hand (13% vs. 29%, p = 0.002) and foot (12% vs. 24%, p = 0.011) nail toxicities. These results were supported by evaluations from a dermatologist blinded to treatment, showing a significant reduction in the DNT score for the cryotherapy group at week 8 (29.4 [95% CI, 17 to 41.8] vs. 54.9 [95% CI, 42.7 to 67.2]; p < 0.001) and at week 24 (9.5 [95% CI, 3.1 to 22] vs. 22.8 [95% CI, 10.3 to 35.3]; p = 0.025). Severe discomfort and pain were reported by 41% and 35% of patients wearing frozen gloves, and by 43% and 42% of patients using frozen socks, respectively. PROs revealed no significant differences in quality of life between the treatment arms at weeks 8 and 24. Cryotherapy effectively reduces the incidence and severity of nail toxicity in eBC patients receiving 3 courses of (neo)adjuvant docetaxel. Although well-tolerated overall, discomfort remains a notable limitation. These findings support cryotherapy as a scalable intervention to improve chemotherapy tolerability. L. Mathiot, C. Poiraud, J. Dimet, L. Ropers, M. Fenot, E. Bourbouloux, S. Abadie-Lacourtoisie, C. El Kouri, V. Delecroix, R. Lamy, M. Noblecourt, O. Cojocarasu, F. Scotté, J. Frenel, F. Priou. Efficacy of cryotherapy using frozen gloves and socks to prevent docetaxel-induced onycholysis in early breast cancer patients undergoing sequential (neo)adjuvant (F)EC and docetaxel treatment: The Banquise randomized controlled trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-01-04.
Neoadjuvant radiotherapy (RT) is a cornerstone in the management of locally advanced rectal cancer (LARC). With the increasing use of intensity-modulated radiation therapy (IMRT), accurate target delineation and treatment reproducibility are critical. Bladder filling may influence anterior mesorectal displacement. This study prospectively evaluated anterior mesorectal motion under “full” versus “empty” bladder conditions. Forty-eight patients were included. Anterior mesorectal distances relative to bony landmarks were measured at six pelvic levels on planning CT (pCT) and seven cone-beam CTs (CBCTs) acquired during treatment under both bladder protocols. Inter-individual means of intra-individual differences and their standard deviations (SD) were calculated to assess variability. Secondary endpoints included bladder volume reproducibility, an in silico dosimetric comparison, and calculation of anisotropic anterior planning target volume (PTV) margins. Anterior displacements were similar between protocols, with consistent forward motion. Variability decreased from upper to lower rectum. In the upper rectum, bladder filling had little effect (SD: empty 6.48 mm vs. full 5.19 mm). In mid and lower rectum, variability was lower with an empty bladder (mid: 4.60 vs. 5.36 mm; lower: 3.03 vs. 3.45 mm). Bladder volume was poorly reproducible under full-bladder conditions (mean 243 cm3, SD 164 cm3) but consistent with empty bladder instructions (mean 73 cm3, SD 58 cm3). Dosimetric analysis showed slightly higher organ-at-risk doses with an empty bladder, remaining within national constraints. An empty bladder protocol with anisotropic margins improves treatment reproducibility while maintaining dosimetric safety in LARC patients.
Background Maintenance niraparib at an individualized starting dose (ISD) is established in platinum-sensitive recurrent ovarian cancer (PSROC). However, patients' perspectives on the burden of prolonged maintenance therapy have not been reported in prospective trials or routine practice.Methods In the real-life multicenter NiQoLe study, patients with PSROC received ISD maintenance niraparib. The primary objective was to describe physician-reported adverse events (AEs) leading to treatment modification during the first 3 months. Secondary endpoints included patient-reported outcomes (symptomatic AEs using PRO-CTCAE, self-reported fatigue, and impact on daily activities/function using FACT-F) collected remotely weekly using a specifically designed electronic device.Results Most (80%) of 139 treated patients (median age = 70 years) began niraparib at 200 mg/day. Median treatment duration was 5.7 (range = 0.2-21.4) months. During the first 3 months, 86 patients (62%) required treatment modification (median = 27 days to modification). Physician-reported grade >= 3 niraparib-related AEs occurred in 34 patients (24%); 68 patients (49%) had treatment modification for AEs, predominantly thrombocytopenia. The most frequent patient-reported AEs (PRO-CTCAE) were fatigue, insomnia, constipation, and dry mouth. Self-reported AEs were severe in 66% of patients. At baseline, 33% of patients reported severe fatigue (FACT-F), which generally persisted during niraparib. Physicians systematically underestimated major patient-reported symptoms.Conclusions In routine practice, niraparib dose modification was often required during the first 3 months despite individualized dosing. Physicians underestimated the burden of fatigue and symptomatic AEs. Digital self-reporting of AEs is feasible, provides patient-centered information complementing physician-reported AEs, and allows fuller appreciation of toxicity in real-world studies.Clinical trial information NCT03752216
