1017 Background: Endocrine therapy (ET) plus Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) is the standard 1 st line treatment for patients (pts) with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative, advanced Breast Cancer (HR+/HER2- aBC). ET+CDK4/6i continuation beyond progressive disease (PD) detection, plus/minus locoregional therapies, is often used in clinical practice for selected pts with oligoprogressive disease or minimal PD. However, the effectiveness of this approach has never been investigated in large studies. Methods: In this analysis of the multicenter, real-world study PALMARES-2 (NCT06805812), we evaluated clinical characteristics and outcomes in HR+/HER2- aBC pts who continued 1 st line ET+CDK4/6i after detection of PD, as defined by physicians based on clinical-radiological assessment. The primary endpoint was real-world progression-free survival (rwPFS) beyond PD, defined as the time between the detection of the first PD event during 1 st line ET+CDK4/6i and the occurrence of subsequent PD leading to definitive ET+CDK4/6i discontinuation, or patient death. We used multivariable Cox regression models to explore the association of 15 covariates with rwPFS beyond PD. We also assessed real-world overall survival (rwOS), as defined as the time between 1 st line ET+CDK4/6i initiation and patient death. Results: Of 4,236 consecutive pts who initiated ET+CDK4/6i between January 2016 and September 2024 in 27 Italian Institutions, 2,434 pts experienced a PD event. Of these pts, 454 (18.7%) continued the same ET+CDK4/6i beyond PD and underwent radiotherapy (n = 306; 67%), surgery (n = 39; 9%), other locoregional treatments (n = 28; 6%) or no local therapies (n = 81; 18%). Pts continuing ET+CDK4/6i beyond PD were more likely to be younger and premenopausal, to have higher tumor estrogen receptor (ER) and/or progesterone receptor (PgR) expression, to have bone/lymph node metastases, and less likely to have liver metastases (p < 0.05 for all covariates). Median rwPFS beyond PD was 10.5 months (95% CI: 9.7-12). At multivariable analysis, higher tumor ER (p = 0.031)/PgR (p = 0.001) or lower Ki-67 (p < 0.001) expression, better ECOG Performance Status (p = 0.009) and the use of locoregional treatments (p < 0.001) were associated with longer rwPFS beyond PD. Pts continuing ET+CDK4/6i therapy beyond PD had better median rwOS than those discontinuing it after first PD detection (71.3 and 44.7 months, respectively; p < 0.001). Conclusions: This is the largest real-world study to show the effectiveness of 1 st line ET+CDK4/6i continuation beyond PD in HR+/HER2- aBC pts. Our findings support the use of this well-tolerated and effective approach in selected pts, such as those with less biologically aggressive tumors and/or amenable to locoregional therapies. Clinical trial information: NCT06805812 .

Identifying predictive and resistance biomarkers remains one of the most relevant unmet needs in clinical cancer research. Artificial Intelligence (AI) represents a powerful tool to develop predictive algorithms tailored to individual patients. Thanks to its ability to process large quantities of heterogeneous, patient-level information, the AI-based approach is progressively fostering the growth of a data-driven paradigm to complement traditional, hypothesis-driven clinical research. However, the development of reliable AI models requires access to large, high-quality, and continuously updated datasets. Despite this necessity, no infrastructure currently exists to enable federated, multi-omic, standardized, prospective, and large-scale collection and analysis of real-world clinical and biological data in the context of lung cancer. We established the APOLLO11 consortium, a distributed, nationwide, updated Italian lung cancer network designed to build a decentralized, long-term, population-based, real-world data repository and a multilevel biobank, locally stored and centrally annotated. This strategy seeks to lay the foundation for the clinical implementation of data-driven research, ultimately advancing precision oncology.

PURPOSE:We aimed to investigate the prognostic and predictive value of tumor infiltrating lymphocytes (TILs) for adjuvant immunotherapy in high-risk early TNBC. PATIENTS AND METHODS:The phase III A-BRAVE trial randomized 466 patients with high-risk early TNBC to adjuvant avelumab or observation after standard therapy. Inclusion criteria allowed two strata: Stratum A (primary surgery followed by adjuvant chemotherapy, defined at high risk based on pathological stage) and Stratum B (neoadjuvant chemotherapy followed by surgery without pathological complete response). TILs were centrally assessed on treatment-naive tumor samples (BSL-TILs) and on residual disease after neoadjuvant chemotherapy (RD-TILs, Stratum B). Residual cancer burden (RCB) was assessed in Stratum B. Survival endpoints were: disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS:BSL-TILs were available for 387 patients, RD-TILs for 330 patients (290 with both BSL-TILs and RD-TILs). Higher BSL-TILs were independently associated with improved outcomes across all endpoints. In Stratum B, higher RD-TILs showed a significant independent association with improved outcomes, outperforming BSL-TILs. RCB was also independently prognostic. Avelumab improved outcomes only for patients with BSL-TILs ≥30%, particularly in Stratum B (3-yr DDFS rates 92.0% vs 58.7%, HR 0.20 in high BSL-TILs and 70.4% vs 70.1%, HR 0.92 in low BSL-TILs, interaction p=0.019). Similar results for DFS and OS. RCB was not predictive for avelumab benefit. CONCLUSIONS:TILs may predict benefit from adjuvant immunotherapy in early TNBC. These findings warrant validation and support TILs-guided immunotherapy strategies in future trials. TRIAL REGISTRATION:NCT02926196.

Background Diagnostic and Therapeutic Care Pathways (DTCPs) are clinical governance tools aimed at managing the care of specific patient populations through the coordinated application of standardized, evidence-based interventions by multidisciplinary teams. Their primary goal is to ensure equitable, timely, and cost-effective access to high-quality care. Materials and method A panel of recognized opinion leaders, endorsed by the Italian Association of Medical Oncology (AIOM), was convened to develop a consensus document defining the role of the medical oncologist within Multidisciplinary Oncology Groups (MOGs) and DTCPs. Employing the RAND/UCLA Appropriateness Method in its “consensus conference” format, the panel evaluated a series of statements derived from a review of the scientific literature and expert-generated Good Practice Points (GPPs). These statements addressed five key areas.1.Skills of the Oncologist in the diagnostic phase2.Follow up3.Palliative care4.Management of the diagnostic and therapeutic care pathway of the oncological patient5.Medical therapy.To further support each topic, illustrative case studies were presented. Results A total of 21 articles met the inclusion criteria, yielding 88 evidence-based recommendations. Additionally, panel members contributed 9 further GPPs based on clinical expertise. Of the 97 total recommendations, 95 received a relevance score above 7, while 2 scored between 4 and 6.9; none scored below 4. Conclusions This consensus effort and the resulting document represent a comprehensive evaluation of the available evidence regarding the role of medical oncologists within MOGs and DTCPs. The objective is to propose standardized criteria for the optimal management of cancer patients (pts) across all phases of care from initial diagnosis and staging to treatment, follow-up, and end-of-life support.

Supplementary Data of correlation analysis

Purpose: This phase IIIb study prospectively evaluated the prognostic and predictive value of baseline and dynamic circulating tumor DNA (ctDNA) in postmenopausal patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) treated with first-line ribociclib/letrozole.Experimental Design: A total of 287 patients were enrolled, with ctDNA analyzed at baseline (n = 263), day 15 of cycle 1 (C1D15; n = 238), C2D1 (n = 241), and first imaging (n = 206). The primary objective was to identify ctDNA alterations, characterize their evolution across treatment time points, and assess their association with progression-free survival (PFS).Results: Median PFS was 23.4 months (95% confidence interval, 20.8 to not estimable). At baseline, the most frequently altered genes were PIK3CA (22.1%) and TP53 (15.5%). Alterations in TP53, MYC, and HER- and cyclin-dependent kinase 4/6- pathway genes were linked to early progression. Absence of a detectable mutation at baseline (n = 150, 57%) was associated with a better prognosis [hazard ratio (HR) = 0.41]. Among patients with a detectable mutation at baseline (n = 104), early clearance (mutation undetectability) was observed in 47.1% at C1D15 and 52.4% at C2D1 and was associated with improved PFS (C1D15, HR = 0.51; C2D1, HR = 0.44). In patients without a detectable mutation at baseline, 22.7% (n = 34) developed new mutations at C1D15, C2D1, or first imaging. Patients without new mutations had a lower risk of progression (HR = 0.45).Conclusions: Pretreatment and early dynamics of ctDNA represent promising prognostic and predictive biomarkers in patients with HR+/HER2- ABC treated with ribociclib/letrozole. Early ctDNA dynamics seem to be a promising surrogate biomarker for treatment. Further studies are warranted to validate their clinical utility.

1092 Background: Endocrine sensitivity/resistance (ES/ER) is a key prognostic and predictive factor in patients (pts) with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative advanced Breast Cancer (HR+/HER2- aBC). Cyclin Dependent Kinase 4/6 inhibitors (CDK4/6i)+Endocrine Therapy (ET) are standard 1 st line therapy for HR+/HER2- aBC pts regardless of tumor ES/ER status at diagnosis. However, the prognostic value of tumor recurrence dynamics within ES/ER groups has never been investigated. Methods: We conducted a pre-planned analysis of the multicenter, real-world, Italian study PALMARES-2 (NCT06805812) to evaluate the prognostic role of tumor recurrence dynamics, de novo aBC presentation and distant recurrence-free interval (DFRI) in pts with HR+/HER2- aBC treated with 1 st line ET+CDK4/6i between January 2016 and September 2024. DRFI was defined as the time from surgery to the detection of aBC. The primary endpoint was real-world progression-free survival (rwPFS), defined as the time between ET+CDK4/6i initiation and disease progression (PD) or patient death. Results were adjusted through Multivariable Cox regression for 16 relevant covariates. Results: Of 4,234 pts enrolled, 2,858 (67.5%) had ES and 1,376 (32.5%) had ER disease at aBC diagnosis. Median follow-up was 38.6 and 42.7 months, respectively. After adjustment, ER was associated with poorer rwPFS compared to ES (adjusted hazard ratio [aHR] 1.78, 95% CI 1.60-1.96). In the ER cohort, secondary tumor resistance with recurrence during years (y) 3-5 of adjuvant (adj) ET or <1 y from its end, and recurrence during extended adj ET or <1 y from its end, were associated with increasingly better rwPFS when compared to primary resistance (Table). In the ES cohort, pts with tumor recurrence >10 y from adj ET end had significantly longer rwPFS when compared to pts recurring <10 y from adj ET end, or pts with no prior adj ET or de novo aBC (Table). Among pts with recurrent disease (N=2,792), any additional y of DRFI resulted in 3% reduction in the risk of disease progression (aHR:0.97, 95% CI: 0.96-0.99). Conclusions: The current ES/ER classification fails to capture the whole spectrum of prognostic heterogeneity in HR+/HER2- aBC pts treated with 1 st line ET+CDK4/6i. Recurrence dynamics, including DRFI, improve prognostic classification and may inform treatment selection and personalised patient management in this clinical context. Clinical trial information: NCT06805812 . Recurrence dynamic N rwPFS (mo) aHR (95% CI) Primary resistant 334 13.4 Ref Secondary resistant-during 5 y adj ET 668 15.7 0.85 (0.72-0.99) Secondary resistant-during extended adj ET 375 19.4 0.73 (0.61-0.89) No adjuvant ET 288 30.0 0.46 (0.36-0.59) 1-5 y from adj ET end 453 29.3 0.54 (0.45-0.65) 5-10 y from adj ET end 377 32.6 0.50 (0.40-0.61) >10 y from adj ET end 275 45.2 0.30 (0.23-0.40) De novo aBC 1422 31.3 0.50 (0.42-0.59)

Multidisciplinary management of oncological patients has improved patient outcomes, responding effectively and efficiently to the patient’s health needs. A critical element remains adequate communication, also between radiologist and oncologist, which promotes correct patient management. The Italian Society of Medical Oncology (AIOM) and the Italian Society of Medical and Interventional Radiology (SIRM) have created a working group of representative members to improve not only communication between the two categories but, above all, to allow each member of the different categories to benefit from guidelines of good clinical practice both for filling out the examination request form than the radiological report, and therefore, also allowing clinicians and radiologists who do not work in reference centers, to correctly manage patients in the various phases of their oncological path. A panel of expert oncologists (AIOM members) and radiologists (SIRM members) was established. Multi-round consensus-building Delphi exercise was performed to create a comprehensive structured report (SR) template and a comprehensive requesting model for computed tomography (CT). The requesting model was divided into six sections: (a) oncological family history; (b) relevant clinical data; (c) staging; (d) re-staging; (e) other reason; and (f) follow-up. Regarding CT SR, 3 models were proposed: (1) for staging; (2) for treatment evaluation, and (3) for follow-up. CT SR in staging phase was divided into nine sections: (a) primary tumor; (b) lymph node metastases; (c) liver metastases; (d) lung metastases; (e) brain metastases; (f) other organs (incl. skeleton) metastases; (g) peritoneum; (h) incidental findings and complications; and (i) conclusion. CT SR in treatment evaluation phase was divided into ten sections: (a) primary tumor; (b) lymph node metastases; (c) liver metastases; (d) lung metastases; (e) brain metastases; (f) other organs (incl. skeleton) metastases; (g) peritoneum; (h) treatment-related complication; (i) incidental findings; and (l) conclusion. CT SR in follow-up phase was divided into six sections: (a) appearance of lesions; (b) node metastases; (c) liver lesions; (d) peritoneum; (e) incidental findings and complications; and (f) conclusion. Cronbach’s alpha (Cα) correlation coefficient was used to evaluate internal consistency for each item and the quality analysis according to the average inter-item correlation. Each expert expressed individual comments for each specific template section by using a four-point scale (0 = strongly disagree, 1 = slightly disagree, 2 = modestly agree, 3 = strongly agree). With regard to the 3 CT SR reports, at the first round, all sections achieved ratings above the “good” level. The staging items showing the highest level of agreement among experts in the first round were lung metastases and incidental findings and complications. For treatment evaluation, the items with the highest agreement were treatment-related complication and incidental findings. For follow-up, the items with the highest agreement were appearance of lesions and incidental findings and complications. At the first round, Cronbach’s alpha (Cα) correlation coefficients were 0.92, 0.95, and 0.90 for staging, re-staging, and follow-up, respectively. At the second round, all sections achieved ratings at the “excellent” level. Regarding requesting model, at first round, all sections received an overall score equal to or greater than the level defined as “good” (score = 2). The item that showed the highest level of agreement in the first round was the follow-up section, with a mean value of 2.75 ± 0.62. The correlation coefficient, Cronbach’s alpha (Cα), was 0.75. In the second round, for both the CT SR report and the oncologist request template, all elements received “excellent” ratings. During the inter-society agreement, six AIOM members assessed the CT SR model developed by SIRM, while six SIRM members evaluated the CT requesting model proposed by AIOM. In this single Delphi round, all participants assigned the maximum score (3) to every item across all sections. The inter-society collaboration between AIOM and SIRM is a milestone in improving communication between radiologists and oncologists. The CT request and reporting documents meet the needs of quality care even outside of referral centers, and although do not represent an obligation, they can facilitate understanding between the different categories of professionals involved in patient management.

1010 Background: Circadian rhythms regulate immune functions, and morning (AM) administration of immunotherapy (IO) is associated with survival in several solid tumors. However, whether time-of-day (ToDa) of IO delivery influences outcomes in early-stage triple-negative breast cancer (TNBC), and whether this effect depends on immune biomarkers, remains unknown. Methods: A-BRAVE randomized patients with high-risk early-stage TNBC to 1 year of adjuvant avelumab or observation. Infusion time of avelumab was retrieved from eCRF. AM-rate was calculated for each patient as the proportion of the first 4 infusions occurring before 12:30 PM (cohort median ToDa) and patients categorized as AM-dominant (AM-rate ≥50%) or PM-dominant. Tumor-infiltrating lymphocytes (TILs) and PD-L1 (Dako 73-10) were centrally assessed on treatment-naive tumor samples. We analyzed distant disease-free survival (DDFS) and overall survival (OS) by adjusted Cox models. Results: ToDa data were available for 221 avelumab-treated patients (94.0%); TILs and PD-L1 were evaluable in 188 (85%) and 195 (88%) of these, respectively. AM-rate was not associated with outcomes. However, ToDa effects were strongly immune-dependent. Increasing AM-rate was associated with improved DDFS and OS in immune-hot tumors (TILs [≥20%] or PD-L1 [≥21] high), but with worse outcomes in immune-cold tumors (TILs or PD-L1 low) (AM-rate*TILs interaction: DDFS p=0.008, OS p=0.001; AM-rate*PD-L1 interaction: DDFS p=0.030, OS p=0.039). These findings were concordant using AM-dominant vs. PM-dominant categorization (Table). Patients receiving immune-aligned treatment (immune-hot/AM-dominant OR immune-cold/PM-dominant) had superior survival compared with immune-misaligned (immune-hot/PM-dominant OR immune-cold/AM-dominant) and the observational arm (TILs-based: 3-year OS 95.7% vs 75.2% vs 78.0%; p<0.001; PD-L1-based: 3-year OS 93.4% vs 79.4% vs 76.1; p=0.035). Conclusions: In early-stage TNBC, time of IO administration may be a driver of efficacy, with opposing effects according to baseline immune milieu. Immune-informed circadian alignment may represent a previously unrecognized determinant of IO efficacy in TNBC. Clinical trial information: NCT02926196 . Outcome AM-dominant3-yr Rate % (95% CI) PM-dominant3-yr Rate % (95% CI) Log-rank p AM vs PM dominant HR (95% CI) TILs High DDFS 90.1 (81.3–99.8) 72.0 (56.4–91.9) 0.064 0.39 (0.13–1.21) OS 97.5 (92.8–100) 76.0 (61.0–94.7) 0.019 0.35 (0.10–1.20) TILs Low DDFS 63.1 (52.6–75.7) 84.7 (75.5–95.1) 0.003 2.61 (1.23–5.55) OS 74.9 (65.2–86.0) 94.3 (88.3–100) 0.003 3.84 (1.30–11.29) PD-L1 high DDFS 100 (100–100) 61.5 (40.0–94.6) 0.015 0.11 (0.01–0.94) OS 100 (100–100) 76.9 (57.1–100) 0.008 0.11 (0.01–1.03) PD-L1 low DDFS 66.4 (57.3–77.0) 83.0 (74.7–92.2) 0.026 1.82 (1.00–3.31) OS 79.8 (71.9–88.6) 91.5 (85.3–98.2) 0.025 2.05 (0.95–4.43)

EPSCCs represent rare and extremely aggressive tumors. In most cases, with widespread metastatic disease, the incidence rate is between 0.1

BACKGROUND:The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new "grey areas" not covered by international guidelines, where treatment decision making is particularly challenging. METHODS:Sixteen relevant statements regarding the management of HR+ /HER2- mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements. RESULTS:The consensus was reached for all 16 statements: 4 were related to resistance and sensitivity to CDK4/6 inhibitors and endocrine therapy, 6 to biomarkers for HR+ /HER2- mBC, and 6 to treatment algorithm of HR+ /HER2- mBC. The Panel critically and comprehensively discussed the most relevant results, especially regarding the statements with lower level of agreement (which ranged from 85.4 % to 100 %). CONCLUSIONS:The treatment of HR+ /HER2- mBC is currently being reshaped due to the expansion of its pharmacopoeia, the better understanding of its molecular determinants and the validation of biomarkers for patient selection. This consensus addressed the most controversial questions related to treatment decision and reached the agreement in all statements.

Background: The A-BRAVE trial showed an improvement in long-term outcome with the anti-PD-L1 avelumab administered as adjuvant therapy for high-risk early TNBC patients. Here, we report the efficacy of avelumab according to PD-L1, tumor infiltrating lymphocytes (TILs), and residual cancer burden (RCB). Methods: The phase III A-BRAVE trial randomized 466 patients with high risk early TNBC to 1-year avelumab vs observation after completion of standard surgery and neoadjuvant/adjuvant chemotherapy. High risk was defined as high disease burden in case of primary surgery (n=83 Stratum A) or invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (n=383 Stratum B). Avelumab vs observation improved outcomes (Conte P ASCO 2024): +5.1% in 3-yr DFS in ITT and Stratum B (non-significant, co-primary endpoints); +8.5% in 3-yr OS in ITT (p=0.035) and Stratum B (p=0.070); +7.5% in 3-yr DDFS in ITT (p=0.028). Here, we report DFS (secondary endpoint), DDFS and OS by PD-L1 status in ITT, as well as DFS, DDFS and OS by post-neoadjuvant chemotherapy TILs and RCB in Stratum B. PD-L1 was evaluated on surgical tumor samples (Stratum A) and diagnostic core-biopsies (Stratum B) with the IHC 73-10 RUO assay (Agilent Technologies); the % of positive stromal cells/total stromal cells was calculated with digital pathology. PD-L1 high was defined according to a previously published >21% cut-off (Dieci MV, Eur J Cancer 2020). In Stratum B, surgical samples were evaluated for TILs (centrally) and RCB (locally) according to guidelines. Only p values <0.05 are shown. Results: PD-L1 expression was prognostic: every 1% increment was associated with improved DFS (HR 0.99, 95%CI 0.97-1.00, p=0.014), DDFS (HR 0.98, 95%CI 0.97-0.99, p=0.005) and OS (HR 0.99, 95%CI 0.97-1.00, p=0.049). PD-L1 high vs PD-L1 low patients showed better outcome: 3-yr DFS 80.6% vs 64.3%, p=0.004; 3-yr DDFS 85.1% vs 69.8%, p=0.002; 3-yr OS 89.6% vs 79.5%, p=0.032. No significant interaction between PD-L1 and treatment arm was observed for any efficacy endpoint. However, the benefit of avelumab vs control was more evident for PD-L1 low: 3-yr DFS 67.3% vs 61.1%, 3-yr DDFS 73.6% vs 65.9%, 3-yr OS 84.6% vs 74.1% in PD-L1 low; 3-yr DFS 77.1% vs 84.4%, 3-yr DDFS 85.7% vs 84.4%, 3-yr OS 91.4% vs 87.5% in PD-L1 high. In Stratum B, RCB was prognostic. Outcomes by RCB I, II and III were: 3-yr DFS 76.7%, 67.5%, 32.4%; 3-yr DDFS 76.5%, 73.6%, 39.7%; 3-yr OS 83.1%, 81.7%, 46.6%, p<0.001 for all endpoints. No significant interaction for any efficacy endpoint was observed between RCB and treatment arm. The benefit of avelumab vs control by RCB category was: RCB I (n=30, 3-yr DFS 84.6% vs 70.6%; 3-yr DDFS 84.6% vs 70.6%; 3-yr OS 84.6% vs 82.4%), RCB II (n=224, 3-yr DFS 67.3% vs 67.6%; 3-yr DDFS 75.8% vs 71.3%; 3-yr OS 87.4% vs 75.7%), RCB III (n=55, 3-yr DFS 44.6% vs 19.2%, p=0.028; 3-yr DDFS 55.0% vs 23.1%, p=0.003; 3-yr OS 57.5% vs 33.6%, p=0.026). TILs on residual disease were significantly prognostic in Stratum B: every 1% increase was associated with: HR 0.98 95%CI 0.97-0.99, p=0.002 for DFS; HR 0.98 95%CI 0.97-0.99, p=0.004 for DDFS; HR 0.98, 95%CI 0.96-1.00, p=0.010 for OS. Results were similar after correction for RCB. There was no significant interaction for any efficacy endpoint between TILs and treatment arm. The benefit of avelumab vs control was more evident in TILs<10% (3-yr DFS 57.7% vs 50.0%; 3-yr DDFS 64.7% vs 53.6%; 3-yr OS 74.6% vs 61.8%) than TILs>10% (3-yr DFS 72.5% vs 75.4%; 3-yr DDFS 81.5% vs 79.2%; 3-yr OS 89.6% vs 85.6%). Conclusions: Efficacy of avelumab for high-risk TNBC did not significantly differ by PD-L1 in the ITT, or by TILs and RCB in Stratum B. However, these biomarkers help identifying subgroups of patients at poorer prognosis deriving the greatest magnitude of benefit from this treatment. Citation Format: Maria Vittoria Dieci, Giancarlo Bisagni, Lorenzo Nicolé, Peter Schmid, Vittoria Fotia, Federico Piacentini, Adolfo Favaretto, Giulia Bianchi, Saverio Cinieri, Lucia Del Mastro, Domenico Corsi, Michelino de Laurentiis, Grazia Arpino, Marta Mion, Antonino Musolino, Antonella Ferro, Donata Sartori, Fable Zustovich, Simon Spazzapan, Alessandra Gennari, Claudio Zamagni, Stefano Tamberi, Tommaso Giarratano, Elisa Gasparini, Giovanna Magni, Gian Luca De Salvo, Pierfranco Conte, Valentina Guarneri. Efficacy of adjuvant avelumab by PD-L1, tumor infiltrating lymphocytes and residual cancer burden in high-risk triple negative breast cancer: secondary and exploratory endpoints of the phase III A-BRAVE trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr RF3-02.

BACKGROUND:Trastuzumab combined with chemotherapy is a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer in later lines. Lapatinib and trastuzumab have also demonstrated efficacy. This study assessed the efficacy, toxicity, and quality of life (QoL) of trastuzumab plus lapatinib (with endocrine therapy for hormone receptor-positive cases) versus trastuzumab with physician-selected chemotherapy in patients previously treated with at least 2 anti-HER2 regimens. METHODS:In this open-label, multicenter phase II trial, 59 patients were randomized 1:1 to receive either trastuzumab and lapatinib (arm A) or trastuzumab with chemotherapy (arm B). The primary endpoint was clinical benefit rate (CBR), defined as confirmed complete response, partial response, or stable disease for ≥24 weeks. Secondary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), QoL, and safety. RESULTS:With a median follow-up of 57.5 months, the CBR was 20.7% in arm A and 26.7% in arm B (P = .76). The ORR was 13.8% versus 20.0% (P = .73), and median PFS was 3.6 months in arm A versus 6.1 months in arm B (HR 0.63; P = .08). Median OS was 29.9 versus 31.1 months (HR 1.07; P = .82). Adverse events occurred in 86.2% (arm A) and 66.7% (arm B) of patients, with grade 3-4 events in 24.1% and 13.3%, respectively. QoL favored arm A (P = .03). Due to early study closure and limited sample size, all results should be considered exploratory and not powered to assess definitive treatment effects. CONCLUSIONS:While efficacy differences were not significant, trastuzumab with lapatinib showed better QoL despite higher adverse event rates, suggesting it may be a viable chemotherapy-free option for pretreated HER2-positive advanced breast cancer. EUDRACT TRIAL REGISTRATION NUMBER:2013-005044-29.

Introduction:Evaluation of every breast cancer (BC) patient by multidisciplinary team and application of guidelines are very important to ensure the best treatment and achieve the best outcome. Methods:The multicenter prospective observational BRIDE study enrolled, from 01/2018 to 02/2021, 1633 BC patients from 19 Italian cancer centers. To evaluate the clinical and biopathological characteristics of BC patients with pathological stage I-II-III treated with surgery followed by adjuvant systemic therapy, type of therapies delivered, outcome and adherence to guidelines, an analysis of 1123 patients out of 1633 patients enrolled in BRIDE study was conducted. Results:The 1123 patients with stage I-II-III BC had a median age of 61.2 years (Q1-Q3: 50.6-71.7); 70.2% were postmenopausal, 92.1% had ECOG PS 0, 68.4% pT1 disease, 70.7% pN0, 91.7% pathological stage I-II; 68.9% underwent conservative breast surgery and 79.8% sentinel lymph node biopsy alone. According to phenotypic subgroup, 80.6% of patients had a HER2-negative/HR-positive, 10.4% HER2-positive/HR-positive, 6.4% triple negative and 2.6% HER2-positive/HR-negative BC. In clinical practice, the phenotypic tumoral subgroup influenced oncologists in the choice of the type of adjuvant systemic therapy (p<0.0001) according to ESMO and AIOM Guidelines. Adjuvant radiotherapy was administered to 85.5% patients undergoing breast-conserving surgery. At the median follow up of 41.4 months (Q1: 35.3 months - Q3: 57.9 months), the DFS at 48 months was 92.8%, with different rates in the phenotypic subgroups. The adherence to AIOM Guidelines in clinical practice was ≥ 70% for the four evaluated quality indicators of treatment process. Discussion:In patients with pathological stage I-II-III BC, the phenotypic subgroup influenced the oncologists' decision on the choice of type of adjuvant systemic therapy, as also indicated by international and national guidelines. In our patients, the DFS rate at 24 and 48 months after surgery was 95.4% and 92.8% respectively. The adherence to the AIOM Guidelines in clinical practice was high but having both quality indicators (shared at international and national level) to evaluate the quality of care in BC and standardized threshold levels to evaluate adherence to guidelines is very important today because this type of evaluation will increase in the coming years.

BACKGROUND 20% of prostate cancer (PC) patients harbor germinal or somatic alterations in homologous recombination repair (HRR) genes, including BRCA1/2. BRCA mutations represent predictive biomarkers for treatment with polyadenosine diphosphate-ribose inhibitors (PARPi). Olaparib has shown efficacy in metastatic castration-resistant PC (mCRPC) and is currently approved in Italy for mCRPC with BRCA1/2 mutations. National and international guidelines strongly recommend BRCA testing in PC. However, genetic testing presents challenges in clinical practice that may limit access to PARPi. METHODS we conducted a survey directed towards members of the Italian Association of Medical Oncology to highlight the level of implementation of national recommendations and issues associated with genetic testing. Through an anonymous questionnaire, the survey collected clinical data of PC patients undergoing BRCA testing and the main difficulties to face in conducting the analysis. RESULTS The survey was completed by 108 participants (5% of AIOM members). 52.8% of respondents test BRCA in all metastatic PC patients. If tissue analysis is invalid, only 17% use liquid biopsy, and 15.7% always consider a re-biopsy of a metastatic lesion. A quarter of respondents have to outsource genetic testing to another center and 17.6% have a split process between different institutions. Long timelines, lack of a predefined procedure, and unavailability of liquid biopsy represent the main issues based on respondents' opinions. CONCLUSIONS BRCA testing in PC still presents several difficulties in clinical practice that can limit access to PARPi treatment. Better implementation of molecular testing to identify BRCA-mutated patients is crucial for tailored treatment in mCRPC.

Objective:Patient-reported outcomes (PROs) are considered the gold standard for the assessment of subjective symptoms, quality of life (QoL) and patient well-being in both clinical trials and clinical practice. Here, we report key discussions and findings from the 21st National Conference of the Italian Association of Medical Oncology, held in Bologna on 21-22 June 2024, with a focus on the integration and impact of PROs in oncology research and clinical practice. Methods and analysis:Leading national and international experts presented and analysed data regarding the use of PROs in clinical trials and routine oncology care. Topics included the role of electronic PROs (ePROs), digital therapeutics, financial toxicity as a PRO and methodologies for standardising QoL assessment. Insights were drawn from expert presentations, consensus discussions and practical experiences shared during the conference sessions. Results:Experts emphasised that PROs should be included as key endpoints in clinical trials, with timely publication of results and standardised methodologies for analysis and interpretation. The conference highlighted the critical importance of incorporating PROs and QoL measures throughout the cancer care continuum-from screening to survivorship. In clinical practice, PROs improve patient-centred care and communication, particularly when oncologists are trained to interpret QoL data. The use of ePROs was noted as a valuable tool to support digital health interventions. Financial toxicity emerged as a significant PRO, with screening tools recommended to identify and support at-risk patients. Key organisational challenges were identified, including technological barriers, resource constraints and the need for responsive infrastructure to support real-time PRO integration. Conclusion:The implementation of PROs, including ePROs and financial toxicity assessments, is essential for advancing quality cancer care. Standardisation, digital innovation and targeted clinician education are critical to integrating PROs effectively in both research and clinical settings. Addressing infrastructural and technological challenges will be vital for optimising patient outcomes and ensuring optimal care across the cancer journey.

Kaplan–Meier estimates of PFS stratified on Giscar HRD status among inconclusive status of MGMC (n = 43).

List of BRCA variants detected by both GIScar tests and MGMC tests

PFS in patients according to GIScar (left panel) and MGMC scores (right panel).

MGMC and GIScar scores among concordant and discordant HRD classification on the clinical collection (n = 469)