PURPOSE:/objective: Limited pelvic/para-aortic nodal relapse of prostate cancer after radical local treatment remains a major challenge for locoregional salvage strategies. Salvage Elective Nodes radiotherapy (ENRT) is an appealing option, but concerns persist regarding its toxicity. This study evaluates the 18-months toxicity profile of salvage ENRT combined with intermittent androgen deprivation therapy (iADT) in patients with pelvic and para-aortic oligometastatic disease, compared with iADT alone. MATERIAL:/Methods: OLIGOPELVIS-2/GETUG P12 was a prospective, multicenter, randomized phase III trial. Patients were randomized 1:1 to arm A (6-months iADT alone) or arm B (6-months iADT + ENRT: 54 Gy/1.8 Gy per fraction to the pelvic lymph nodes and 66 Gy/2.2 Gy per fraction to pathological nodes). ENRT started after three months of iADT. After analyzing relapse patterns in the OLIGOPELVIS GETUG P07 study, a December 22, 2021 amendment permitted the inclusion of para-aortic lymph nodes and extended irradiation fields up to the renal arteries. Toxicity was defined using NCI-CTCAE v4.0. RESULTS:A total of 256 patients were enrolled across 17 French centers between 12/2018 and 05/2023. The safety population included 127 patients in arm A and 121 in arm B. Eight patients in arm B were excluded as they did not ultimately receive radiotherapy. Prior prostate or prostatic bed irradiation was reported in 57% and 55% of patients, respectively. In arm B, 39 patients also received para-aortic irradiation. At 6 months, grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 2.4% vs 9.9% (p = 0.02) and 0% vs 19.8% (p < 0.001) of patients in arms A and B, respectively. At 18 months, grade ≥ 2 GU toxicity was 4.1% vs 10.7%, (p = 0.04) in arms A and B, respectively, while no difference in GI toxicity was observed. Prior prostate or prostatic bed irradiation did not increase toxicity at any time point. Among patients receiving para-aortic irradiation, compared to those without : grade ≥ 2 toxicity was similar at 6 months (GU: 12.8% vs 8.5%, p = 0.8; GI: 20.5% vs 19.5%, p = 0.9), or at 18 months (GU: 10.3% vs 11%, p = 1.0; GI: 0% vs 6.1%, p = 0.17), though 6 months upper grade ≥ 1 GI disorders were more frequent (25.6% vs 9.8%, p = 0.02). CONCLUSIONS:Eighteen-month toxicity of salvage ENRT with a simultaneous boost to the pathological lymph nodes, associated with 6-months iADT was acceptable, even among patients with prior prostate irradiation or additional para-aortic irradiation (NCT03630666- RCB 2018-A00551-54; FundingPHRC-K 16-129).
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:The management of oligorecurrent pelvic lymph nodes in patients with prostate cancer is debated. Intermittent androgen-deprivation therapy (ADT; IADT) is often proposed. Elective pelvis irradiation (ENRT) may prolong tumor control and decrease subsequent spread. OBJECTIVE:To assess the efficacy of a combination of 6 mo of IADT with or without ENRT to treat patients with oligorecurrent pelvic and para-aortic lymph nodes of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS:The OLIGOPELVIS 2-GETUG P12 trial is a multicenter randomized phase 3 trial, randomizing patients with 1-5 oligorecurrent pelvic and/or para-aortic lymph nodes of prostate cancer between arm A (IADT alone for 6 mo) versus arm B (salvage pelvic image-guided intensity-modulated radiotherapy [IG-IMRT], 54 Gy, 30 fractions to the pelvis and 66 Gy, 30 fractions to the lymph nodes) combined with IADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary outcome is progression-free survival, defined as the time from randomization until a biochemical-clinical failure is detected or death from any cause. In total, 256 patients will be included. RESULTS AND LIMITATIONS:In this population of patients requiring ADT, ENRT may demonstrate antitumoral efficacy while achieving acceptable toxicity and maintaining quality of life. Limitations are mainly inherent to the open-label design of this study. CONCLUSIONS:This phase 3 study will explore the role of salvage pelvic IG-IMRT combined with IADT in patients with oligorecurrent pelvic lymph nodes of prostate cancer in prolonging the first failure-free interval between the first and the second IADT courses. PATIENT SUMMARY:The OLIGOPELVIS 2-GETUG P12 clinical trial assesses short-term (6 mo) androgen-deprivation therapy in association with external beam radiation therapy in men with prostate cancer relapsing to pelvic and para-aortic lymph nodes of prostate cancer. The trial investigates whether radiotherapy targeting pelvic and para-aortic lymph nodes can improve the biological response while maintaining a favorable tolerability profile. TRIAL REGISTRATION:NCT03630666, RCB 2018-A00551-54, date of registration: 2018-12-04.
Combining immunotherapy with chemoradiation is effective in locally advanced cervical cancer. However, the impact of induction combination immunotherapy on immune modulation and treatment response is poorly understood. In this phase II trial (NCT04256213), 40 females with locally advanced cervical carcinoma received one cycle of nivolumab-plus-ipilimumab immunotherapy before standard chemoradiation, followed by maintenance nivolumab. We show, using multiplex-immunofluorescence tissue imaging, a significantly increased CD8+/FOXP3+ cell ratio (primary endpoint; increase of 0.87 cells/mm², P = 0.0164) and proliferative CD8+ T-cell density after one cycle of combination immunotherapy. HOT score (27-gene-based signature identifying immunologically active tumors) also increased significantly (exploratory analysis; 0.17, P < 0.0001). Objective response rates (secondary endpoint) were 13
