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Background Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. Methods In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). Conclusions Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. Clinical Trial registration Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer. We did this open-label, randomised phase 2 trial at 11 hospitals in Italy. We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy, Eastern Cooperative Oncology Group performance status 0–1, and no residual peripheral neurotoxicity. Patients were randomly assigned (1:1) to receive weekly paclitaxel 80 mg/m2 with or without pazopanib 800 mg daily, and stratified by centre, number of previous lines of chemotherapy, and platinum-free interval status. The primary endpoint was progression-free survival, assessed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01644825. This report is the final analysis; the trial is completed. Between Dec 15, 2010, and Feb 8, 2013, we enrolled 74 patients: 37 were randomly assigned to receive paclitaxel and pazopanib and 37 were randomly assigned to receive paclitaxel only. One patient, in the paclitaxel only group, withdrew from the study and was excluded from analyses. Median follow-up was 16·1 months (IQR 12·5–20·8). Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group (median 6·35 months [95% CI 5·36–11·02] vs 3·49 months [2·01–5·66]; hazard ratio 0·42 [95% CI 0·25–0·69]; p=0·0002). We recorded no unexpected toxic effects or deaths from toxic effects. Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group. The most common grade 3–4 adverse events were neutropenia (11 [30%] in the pazopanib group vs one [3%] in the paclitaxel group), fatigue (four [11%] vs two [6%]), leucopenia (four [11%] vs one [3%]), hypertension (three [8%] vs none [0%]), raised aspartate aminotransferase or alanine aminotransferase (three [8%] vs none), and anaemia (two [5%] vs five [14%]). One patient in the pazopanib group had ileal perforation. Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted. National Cancer Institute of Napoli and GlaxoSmithKline.

Background EPSCCs represent rare and extremely aggressive tumors. In most cases, with widespread metastatic disease, the incidence rate is between 0.1% and 0.4%, and the median survival of less than one year. At present, chemotherapy is considered the only therapeutic strategy in the extensive stage of EPSCC. Methods/design This is an open-label, multicenter, Italian phase II single-arm trial in which patients with extensive-stage EPSCC will receive first-line therapy with intravenously durvalumab (day 1) plus carboplatin or cisplatin, and etoposide (day 1–3) every 3 weeks for 4 or 6 cycles, as investigator’s choice, followed by maintenance with durvalumab every 4 weeks for a maximum of 24 months. Durvalumab will be administered at a fixed dose of 1500 mg, cisplatin at 75 to 80 mg/m2 (day 1), carboplatin AUC 5–6 (day 1), and etoposide at 80–100 mg/m2 daily on days 1 to 3 every 3 weeks. The primary endpoint is the 12-month PFS. The study hypothesis is to detect an increase of at least 10% points compared to standard chemotherapy alone. Secondary endpoints include ORR, DoR, safety, and QoL. Collateral translational studies evaluate (i) whole-exome sequencing and gene expression profiling, and (ii) genetic alterations by circulating free DNA obtained from plasma samples. The trial is an ongoing enrollment; 21 of 66 planned patients have been enrolled. Discussion Considering the efficacy of immunotherapy plus chemotherapy in extensive SCLC and the low incidence of EPSCCs that limits the conduct of randomized trials, this therapeutic approach could be considered for the first time as an agnostic indication based on tumor histology, regardless of the tumor site. The DURVASCC study aims to demonstrate the role of anti-PDL1 antibody in combination with chemotherapy in first-line therapy of ES-EPSCC patients as a histology-related agnostic choice. Trial registration ClinicalTrials.gov: NCT06464068, June 18, 2024.

Background Obesity is a risk factor for breast cancer (BC) development, recurrence, and death. In view of this, we aimed to investigate the clinical value of obesity in BC patients treated with anti-HER2 therapies in the NeoALTTO trial, which randomized 455 patients to neo-adjuvant lapatinib, trastuzumab, or their combination plus paclitaxel. Methods Patients were classified according to their basal body mass index (BMI) into underweight (< 18.5 kg/m 2 ), normal (≥ 18.5; < 25 kg/m 2 ), overweight (≥ 25; < 30 kg/m 2 ), and obese (≥ 30 kg/m 2 ) WHO categories. Univariate and multivariate logistic regression analyses were performed using BMI as a categorical variable. Pathological complete response (pCR) and event-free survival (EFS) were the NeoALTTO primary and secondary outcomes, respectively. Results Among 454 patients analyzed, 14 (3%), 220 (48%), 137 (30%), and 83 (18%) were classified as underweight, normal weight, overweight, and obese, respectively; 231 (51%) and 223 (49%) had hormone receptor (HR)-positive and HR-negative primary tumors; 160 (35%) achieved pCR. In the overall patient population, no association was found between BMI groups and pCR, as we reported pCR rates of 57.1%, 35%, 30.7%, and 39.8% in underweight, normal weight, overweight, and obese cases, respectively. In contrast, in HR-positive tumors, overweight or obesity was generally associated with decreased likelihood of achieving a pCR independently of other clinical variables, including planned surgery, nodal status, and tumor size (odds ratio [OR] = 0.55, 95%CI 0.30–1.01, as compared to normal or underweight; p  = 0.053); notably, no differential effect of BMI with respect to pCR was observed in HR-negative cases (odds ratio [OR] = 1.30, 95%CI 0.76–2.23, as compared to normal or underweight; p  = 0.331), resulting in a statistically significant interaction between BMI and HR status ( p  = 0.036). There was no association between BMI and EFS neither in the overall nor in the HR-positive population, but this analysis was under-powered. Conclusions NeoALTTO patients overweight or obese at baseline and with HR-positive primary BC appeared less likely to achieve pCR after neo-adjuvant anti-HER2 therapies. This finding paves the way to future research in targeting the interplay between HER2/HR signaling and metabolism.

Dihydropyrimidine dehydrogenase (DPYD) is a highly polymorphic gene and classic deficient variants (i.e., c.1236G>A/HapB3, c.1679T>G, c.1905+1G>A and c.2846A>T) are characterized by impaired enzyme activity and risk of severe adverse drug reactions (ADRs) in patients treated with fluoropyrimidines. The identification of poor metabolizers by pre-emptive DPYD screening may reduce the rate of ADRs but many patients with wild-type genotype for classic variants may still display ADRs. Therefore, the search for additional DPYD polymorphisms associated with ADRs may improve the safety of treatment with fluoropyrimidines. This study included 1254 patients treated with fluoropyrimidine-containing regimens and divided into cohort 1, which included 982 subjects suffering from gastrointestinal G≥2 and/or hematological G≥3 ADRs, and cohort 2 (control group), which comprised 272 subjects not requiring dose reduction, delay or discontinuation of treatment. Both groups were screened for DPYD variants c.496A>G, c.1236G>A/HapB3, c.1601G>A (DPYD*4), c.1627A>G (DPYD*5), c.1679T>G (DPYD*13), c.1896T>C, c.1905 + 1G>A (DPYD*2A), c.2194G>A (DPYD*6), and c.2846A>T to assess their association with toxicity. Genetic analysis in the two cohorts were done by Real-Time PCR of DNA extracted from 3 ml of whole blood. DPYD c.496A>G, c.1601G>A, c.1627A>G, c.1896T>C, and c.2194G>A variants were found in both cohort 1 and 2, while c.1905+1G>A and c.2846A>T were present only in cohort 1. DPYD c.1679T>G and c.1236G>A/HapB3 were not found. Univariate analysis allowed the selection of c.1905+1G>A, c.2194G>A and c.2846A>T alleles as significantly associated with gastrointestinal and hematological ADRs (p < 0.05), while the c.496A>G variant showed a positive trend of association with neutropenia (p = 0.06). In conclusion, c.2194G>A is associated with clinically-relevant ADRs in addition to the already known c.1905+1G>A and c.2846A>T variants and should be evaluated pre-emptively to reduce the risk of fluoropyrimidine-associated ADRs.

ObjectivesTo measure and explain financial toxicity (FT) of cancer in Italy, where a public healthcare system exists and patients with cancer are not expected (or only marginally) to pay out-of-pocket for healthcare.SettingTen clinical oncological centres, distributed across Italian macroregions (North, Centre, South and Islands), including hospitals, university hospitals and national research institutes.ParticipantsFrom 8 October 2019 to 11 December 2019, 184 patients, aged 18 or more, who were receiving or had received within the previous 3 months active anticancer treatment were enrolled, 108 (59%) females and 76 (41%) males.InterventionA 30-item prefinal questionnaire, previously developed within the qualitative tasks of the project, was administered, either electronically (n=115) or by paper sheet (n=69).Primary and secondary outcome measuresAccording to the protocol and the International Society for Pharmacoeconomics and Outcomes Research methodology, the final questionnaire was developed by mean of explanatory factor analysis and tested for reliability, internal consistency (Cronbach’s α test and item-total correlation) and stability of measurements over time (test–retest reliability by intraclass correlation coefficient and weighted Cohen’s kappa coefficient).ResultsAfter exploratory factor analysis, a score measuring FT (FT score) was identified, made by seven items dealing with outcomes of FT. The Cronbach’s alpha coefficient for the FT score was 0.87 and the item-total correlation coefficients ranged from 0.53 to 0.74. Further, nine single items representing possible determinants of FT were also retained in the final instrument. Test–retest analysis revealed a good internal validity of the FT score and of the 16 items retained in the final questionnaire.ConclusionsThe Patient-Reported Outcome for Fighting FInancial Toxicity (PROFFIT) instrument consists of 16 items and is the first reported instrument to assess FT of cancer developed in a country with a fully public healthcare system.Trial registration numberNCT03473379.

ObjectivePatient-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 analysisLeading 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.ResultsExperts 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.ConclusionThe 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.

Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients enrolled in the phase II, multicenter TREnd trial. Our results indicate that there is limited benefit from post-palbociclib treatment, regardless of the type of therapy received. A small population of long responders were identified who demonstrated ongoing benefit from a subsequent line of endocrine therapy after progression to palbociclib-based regimens. A translational research program is ongoing on this population of outliers.