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Introduction: Cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) regimen activity was assessed in a single institution phase II trial (PACT-19) on pancreatic ductal adenocarcinoma (PDAC). The PACT-31 study explored the external validity of PACT-19 results., Materials and Methods: Patients aged ≥18 and ≤75 years with KPS ≥70, and PDAC diagnosis receiving PAXG in the participating institutions were eligible and categorized as follows: A) PACT-19; B) PACT-31-HSR; C) PACT-31-non-HSR. With a sample of 175 patients, assuming a target 1-year overall survival of 60 % for metastatic and of 80 % for non-metastatic patients, the trial will be considered successful with the 1-year OS falling into the 95 % CI., Results: Data from 68 PACT-19 and 168 PACT-31 patients were retrieved. After 124 events, 1yOS was 52.5 % (95 %CI: 44.6-60.4 %) for metastatic and 80.5 % (95 %CI: 71.9-89.1 %) for non-metastatic patients. Survival overlapped between PACT-19 and PACT-31-HSR (median 17.6 and 17.4 months, p = 0.21) and was significantly shorter in PACT-31-non-HSR (median 11.3 months; p = 0.03). Differences of dose-intensity, use of maintenance therapy, and treatment after progression between PACT-31-HSR and non-HSR were evidenced., Discussion: PACT-19 results have external validity. The outcome difference between HSR and non-HSR centers endorses the need of creating a hub-and-spoke network aimed at sharing the expertise on rare-diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization., Methods: In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the objective response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA technologies., Results: Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) versus males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower ORR in F versus M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS., Conclusions: Serum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNF-ɑ, and sPD-L1 had a significant sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex., (© 2024. The Author(s).)

Background & Aims: Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid tumours., Methods: Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative aetiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure., Results: In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI 11.1-14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p <0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96)., Conclusions: Despite higher incidence and earlier onset, irLI in patients with HCC is characterised by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumours), low risk of hepatic decompensation and treatment discontinuation, not negatively affecting oncological outcomes., Impact and Implications: Immune-related liver injury (irLI) is common in patients with cancer receiving immune checkpoint inhibitors (ICIs), but whether irLI is more frequent or it is associated with a worse clinical course in patients with hepatocellular carcinoma (HCC), compared to other tumours, is not known. Herein, we compared characteristics and outcomes of irLI in two prospective cohorts including patients treated with ICIs for HCC or for other oncological indications. irLI is significantly more common and it occurs earlier in patients with HCC, also after adjustment for duration of treatment exposure. However, outcomes of patients with HCC who developed irLI are not negatively affected in terms of requirement for corticosteroid therapy, hepatic decompensation, treatment discontinuation and overall survival., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with RAS / BRAF wild-type metastatic colorectal cancer (mCRC)., Patients and Methods: PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable RAS / BRAF wild-type mCRC. Patients were randomly assigned 1:1 to mFOLFOX + PAN (arm A) or 5-FU + LV + PAN (arm B) for up to 12 cycles, followed by PAN maintenance. The primary end point was progression-free survival (PFS). In each arm, assuming a null hypothesis of median PFS time ≤ 6 months and target PFS ≥9.65, 90 patients per arm were needed to achieve 90% power and 5% type I error (one-sided Brookmeyer-Crowley test)., Results: Between July 2016 and April 2019, 91 patients were randomly assigned to arm A and 92 to arm B. At a median follow-up of 50.0 months (IQR, 45.6-56.4), median PFS was 9.6 and 9.0 months for arm A and B, respectively ( P < .001 in each arm). Overall response rate was 69% and 52%, whereas median overall survival was 23.5 and 22.0 months in arm A and B, respectively. The overall rate of grade >2 chemotherapy-related adverse events was 60% and 37%, respectively. Baseline G8 and Chemotherapy Risk Assessment Scale for High-Age Patients scores were prognostic, but they were not associated with efficacy and safety of the two arms., Conclusion: Both mFOLFOX and 5-FU + LV + PAN are reasonable options as initial therapy of elderly patients with RAS / BRAF wild-type mCRC. 5-FU + LV + PAN is associated with a better safety profile.

Background: The clinical value of tumor infiltrating lymphocytes (TILs) in hormone receptor-positive (HR+)/HER2- breast cancer (BC) may be unearthed by focusing on more biologically aggressive tumors. Here we deepen and describe the correlation between RS and TILs, proposing an immuno-genomic model for HR+ /HER2- BC., Methods: We enrolled T1-T3, N0-N1 BC patients with available RS® and TILs in the context of four multicenter, prospective studies. RS® and TILs were considered as continuous and categorical variables. RS® was categorized into: 0-10 (low risk), 11-25 (intermediate risk) and 26-100 (high risk); TILs were categorized into: low TILs (0-10%), intermediate TILs (11-59%) and high TILs (60-100%)., Results: 811 patients were included. RS distribution was (n = 810): low risk 22.0%, intermediate risk 61.2%, high risk 16.8%. TIL distribution was (n = 455): low TILs 84.6%, intermediate TILs 13.6% and high TILs 1.8%. A significant, weak positive, linear correlation was found between continuous TILs and RS (Pearson coefficient=0.223, p < 0.001). When considering RS and TILs categories, tumors with intermediate/high TIL levels significantly enriched the high RS subgroup (p = 0.006). This was confirmed both within Luminal A and Luminal B cohorts. Among high-RS patients, 16.7% of Luminal A and 26.7% of Luminal B tumors had intermediate/high TILs., Conclusions: We observed that RS® and TILs capture only slightly overlapping information on the biology of HR+ /HER2- tumor microenvironment. We demonstrated the feasibility of combining RS and TILs into a composite immuno-genomic model, which may serve the purpose of guiding and focalizing patient selection in the further development of immunotherapy strategies for Luminal-like disease., Competing Interests: Declaration of Competing Interest FM: reports personal fees from Roche, Novartis, Gilead, Seagen, Pfizer, outside the submitted work. MVD: reports personal fees from EliLilly, Exact Sciences, Novartis, Pfizer, Seagen, Gilead, MSD, AstraZeneca, Daiichi Sankyo, and Roche outside of the submitted work. TG: reports personal fees from Gilead, Roche, outside the submitted work. MG: Consulting/Advisor: Roche, AstraZeneca, Lilly, Daichii Sankyo, Novartis, Pfizer, Seagen, MSD, Eisai; Honoraria: Novartis, Pfizer, Lilly, AstraZeneca, Daichii Sankyo; Research funding to the Institution: AstraZeneca; Travel, accommodation, expenses: Lilly, Pfizer, AstraZeneca. MM: personal fees from Accord, Gentili, Novartis, Lilly. EB: received speakers’ and travels’ fee from MSD, Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis and Roche. AZ: reports personal fees and non-financial support from Novartis, Astra-Zeneca, Eli-Lilly, Pfizer, Daiichi Sankyo, MSD, Roche, Seagen, Exact Sciences, Gilead, all disclosures are outside the submitted work. VG: reports personal fees for advisory board membership for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre; personal fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis, Roche and Zentiva; personal fees for expert testimony for Eli Lilly. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs)., Methods: We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion., Results: Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85)., Conclusion: The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs., (© 2023. The Author(s).)

The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) have been reported as prognosticators in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. This analysis of the INVIDIa-2 study on influenza vaccination in patients with cancer treated with immune checkpoint inhibitors (ICIs) assessed NLR and SII on overall survival (OS) by literature-reported (LR), receiver operating characteristic curve (ROC)-derived (ROC) cutoffs or as continuous variable (CV). NLR and SII with ROC cutoffs of <3.4 (p < 0.001) and <831 (p < 0.001) were independent factors for OS in multivariate analysis. SII with LR, ROC, or CV significantly predicted OS in NSCLC (p = 0.002, p = 0.003, p = 0.003), RCC (p = 0.034, p = 0.014, p = 0.014), and melanoma (p = 0.038, p = 0.022, p = 0.019). NLR with LR and ROC cutoffs predicted OS in first line (p < 0.001 for both) and second line or beyond (p = 0.006 for both); likewise SII (p < 0.001; p = 0.002 and p < 0.001). NLR and SII are prognosticators in NSCLC, RCC, and melanoma treated with ICIs., Competing Interests: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study from Roche S.p.A. and Seqirus, and outside the present research from AstraZeneca, Bristol-Myers Squibb (BMS), and Sanofi. G.L.B. received fees for speaker bureau from AstraZeneca and Astellas Pharma. M.B. received funding for the present study from Roche S.p.A. and Seqirus (through FICOG as Institution, no personal fees). She also received, outside the current work, research funding from Pfizer and Novartis (through Institutions); honoraria as a speaker at scientific events (personal fees) by BMS, MSD, IPSEN, Novartis, AstraZeneca, Pierre Fabre, and Pfizer; as a consultant for advisory role (personal fees) from IPSEN, Novartis, Sanofi, Pierre-Fabre, and Merck; and personal fees for copyright transfer from Sciclone Pharmaceuticals, Pierre-Fabre, MSD, IPSEN, Pfizer, and Sanofi. S.B. received honoraria as a speaker at scientific events and in advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. A.C. received speaker fees and grant consultancies by AstraZeneca, MSD, IQVIA, OncoC4, and EISAI. U.D.G. has served as a consultant for Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi, and Pharmamar; he received research funding from AstraZeneca, Roche, and Sanofi; and received travel funds from BMS, Ipsen, Janssen, Pfizer, and Roche during the conduct of the study. P.E. received honoraria for advisory role from MSD, BMS, and Astellas. F.G. received honoraria for advisory role from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, BMS, MSD, Novartis, Merck, Otsuka, Novartis, Takeda, and Bayer; seminar/talks to industry from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, Pierre Fabre, AMGEN, Celgene, BMS, and MSD; and research funding from AstraZeneca, BMS, and MSD. M.D.M. reports personal fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Takeda; has been local principal investigator for trials sponsored by Beigene, Exelixis, Merck Sharp & Dohme, and Pfizer; and received research grant, institutional and financial support, and drug supply for the Meet-URO12 trial from Tesaro GlaxoSmithKline. D.G. received honoraria from Amgen for speaker bureau. M.M. received honoraria for advisory role from MSD and travel and accommodation expenses from Janssen, Roche, and Pfizer. C.P. received honraria for advisory role, speaker bureau, and travel and accommodation expenses from Amgen, Astellas, AstraZeneca, Bayer, Bristol Meyer Squibb, Celgene, Clovis Oncology, Eisai, Ipsen, Janssen, Incyte, Merck-Serono, Merck Sharp & Dohme, Novartis, Roche, Sandoz, Sanofi, and Servier. P.R. received honoraria for advisory role from AstraZeneca, Janssen, Gilead, BMS, and MSD Italy. M.R. received honoraria for advisory role or speaker bureau from Pfizer, Novartis, MSD, AstraZeneca, Bristol-Myers Squibb (BMS), and Merck. V.S. participated, with personal fees, in advisory boards and speaker’s bureaus for Roche S.p.A. S.C. declared his role in an international board for Eli Lilly international. M.S. received honoraria for advisory role from Janssen and grants for participation at scientific events from BMS, Ipsen, Janssen, Astella, Sanofi, Pfizer, and Novartis. E.V. received honoraria for advisory role from MSD, AstraZeneca, Ipsen, and Janssen. P.A.Z. acts in a consultant or advisory role for Sanofi, BMS, Pfizer, MSD, Astellas, Janssen, Ipsen, and Novartis, all outside the scope of work. A.A. undertook consulting or advisory roles from BMS, AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer, Eli Lilly, and Astellas and participated in speaker’s bureaus from Eli Lilly and AstraZeneca. All other authors declare no competing interests., (© 2023 The Authors.)

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration., Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR)., Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007)., Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity., Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus., Competing Interests: The Federation of Italian Cooperative Oncology Groups (FICOG) received funding for the present study from Roche S.p.A. and Seqirus, and outside the present research from Astra Zeneca, Bristol-Myers Squibb (BMS), and Sanofi. MB received funding for the present study from Roche S.p.A. and Seqirus (through FICOG as Institution, no personal fees). She also received, outside the current work: research funding from Pfizer and Novartis (through Institutions); honoraria as a speaker at scientific events (personal fees) by BMS, MSD, IPSEN, Novartis, Astra Zeneca, Pierre Fabre, and Pfizer; as a consultant for advisory role (personal fees) by IPSEN, Novartis, Sanofi, Pierre-Fabre, and Merck; personal fees for copyright transfer by Sciclone Pharmaceuticals, Pierre-Fabre, MSD, IPSEN, Pfizer, and Sanofi. AC received speakers fees/grant consultancies from Astrazeneca, BMS, MSD, EISAI, IQVIA, and OncoC4. UDG has served as a consultant for Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Pfizer, Sanofi, and Pharmamar; he received research funding from AstraZeneca, Roche, and Sanofi; and received travel funds from BMS, Ipsen, Janssen, Pfizer, and Roche during the conduct of the study. MDM reports personal fees from Bristol Myers Squibb, personal fees from Merck Sharp & Dohme, personal fees from AstraZeneca, personal fees from Janssen, personal fees from Astellas, personal fees from Pfizer, personal fees from Eisai, personal fees from Takeda, grants from Tesaro GSK, outside the submitted work. SB received honoraria as a speaker at scientific events and in advisory role by BMS, Pfizer; MSD, Ipsen, Roche S.p.A., Eli-Lilly, AstraZeneca, and Novartis; he also received research funding from Novartis. VS participated, with personal fees, to advisory boards and speaker's bureaus for Roche S.p.A. SC declared his role in an international board for Eli Lilly international. AR declares Advisory Board activity for Bristol, Pfizer, Bayer, and Kyowa Kirin, and speaker honorarium from Roche Diagnostics. PAZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme (MSD), Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, AstraZeneca, Roche, and Bayer. MS received honoraria for advisory role from Janssen, and travel and accommodation expenses from Janssen, IPSEN, BMS, Astellas, and Pfizer. ER had a role as consultant for MSD, Novartis, Pierre Fabre, Immunocore and Pfizer. FG received personal fees from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, MSD, BMS, Pierre Fabre, Novartis, Merck, Takeda, Bayer, Novartis, and AMGEN for consulting activity; from Eli Lilly, Roche, Boehringer Ingelheim, AstraZeneca, BMS, AMGEN, MSD, Celgene, and Pierre Fabre for speakers bureaus. GG declares speaker and advisory fees from MSD; Travels and Accommodations from AstraZeneca. DaS declares honoraria for advisory board from Astellas, Janssen, Bayer, Novartis, Astra-Zeneca, MSD, BMS, Roche. FM received personal fees for advisory role by Roche, MSD, Takeda, Novartis, Sanofi. RRS received travel grants from AIOM and CIPOMO, and declares memberships in AIOM, CIPOMO, ESMO, ASCO and Rotary Club. SP received honoraria as a speaker from Roche, Astra Zeneca, MSD, and GSK. DG received honoraria as a speaker from Amgen. MR received honoraria as speaker/consultant by MSD, Astra Zeneca, Bristol-MyersSquibb (BMS), Novartis, and Pfizer. All the cited competing interests were outside the current work and not related to the content of our manuscript if not differently specified. All remaining authors have declared no conflicts of interest., (© 2023 The Authors.)

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available., Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years., Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles., Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning effectiveness, and strongly invite further research., Competing Interests: LP received speaker fees from Novartis, outside the submitted work. UDG: Pfizer, BMS, MSD, PharmaMAR, AStellas, Bayer, Ipsen, Novartis; Invited speaker Roche, BMS, SAnofi, AstraZeneca; received research grants from AstraZeneca, SAnofi, Roche, outside the submitted work. AF received honoraria as a speaker from Eli Lilly, Novartis, Pierre-Fabre, outside the submitted work. GT: advisory boards from Novartis, Pfizer, Eisai, Roche, and Eli Lilly, outside the submitted work. DS: advisory boards from Novartis, Pfizer, Eisai, Roche, and Eli Lilly, outside the submitted work. NLV: Roche, MSD, Eisai, Novartis, AstraZeneca, GSK, Pfizer, Gentili, Daiichi Sankyo, Dephaforum, outside the submitted work. OG: Eisai, MSD, Gilead, Seagen, Novartis, Eli Lilly, outside the submitted work. IM: advisory boards from Eli Lilly, Novartis, Gentili, Roche, Pfizer, Ipsen, and Pierre-Fabre, outside the submitted work. GD’A: Novartis, Amgen, Eli Lilly outside the submitted work. TG received travel grants from Eisai, Roche, Pfizer, and Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, and Eli Lilly, outside the submitted work. MPi Consultant/advisory boards from Gilead, Eli Lilly, Pfizer, Novartis, Gentili, MSD, outside the submitted work. RB received research grant/advisory boards from AstraZeneca, Boehringer Ingelheim, Novartis, MSD, Otsuka, Eli Lilly, Roche, Amgen, GSK, Eisai, outside the submitted work. FGi: advisory boards from Gilead, Daiichi Sankyo, Seagen, outside the submitted work. MEC consultant/advisory role for Pierre-Fabre, Roche, Novartis, Eli Lilly, Celgene, outside the submitted work. RT: AstraZeneca, Eisai, Pfizer, Eli Lilly, MSD, Exact Science, outside the submitted work. AB: MSD, BMS, Pfizer, Novartis, Roche outside the submitted work. AM received travel grants from Eisai, Celgene, and Novartis Ipsen; personal fees/advisory boards from Eisai, Novartis, AstraZeneca, Teva, Pfizer, and Celgene, outside the submitted work. IP received personal fees/advisory boards from Roche, Pfizer, Novartis, Italfarmaco, Gentili, and Pierre-Fabre. LG received congress travel accomodation from Roche, Daiichi Sankyo, AstraZeneca, Pfizer, Novartis; advisory role for Astra Zeneca outside the submitted work. MMin: Novartis, MSD, Eli Lilly, outside the submitted work. LM received personal fees/advisory board from Roche, Novartis, Eisai, and Pfizer, outside the submitted work. EC: Astellas, Roche, BMS, Jansen, MSD, Sirtex, Merck, Bayer, Servier, Novartis, outside the submitted work. PM has/had a consultant/advisory role for BMS, Roche, Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre-Fabre and Incyte, outside the submitted work. PV received speaker fees/advisory boards from Roche, Pfizer, Novartis and Eli Lilly, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Di Lisa, Krasniqi, Pizzuti, Barba, Cannita, De Giorgi, Borella, Foglietta, Cariello, Ferro, Picardo, Mitidieri, Sini, Stani, Tonini, Santini, La Verde, Gambaro, Grassadonia, Tinari, Garrone, Sarobba, Livi, Meattini, D’Auria, Vergati, Gamucci, Pistelli, Berardi, Risi, Giotta, Lorusso, Rinaldi, Artale, Cazzaniga, Zustovich, Cappuzzo, Landi, Torrisi, Scagnoli, Botticelli, Michelotti, Fratini, Saltarelli, Paris, Muratore, Cassano, Gianni, Gaspari, Veltri, Zoratto, Fiorio, Fabbri, Mazzotta, Ruggeri, Pedersini, Valerio, Filomeno, Minelli, Scavina, Raffaele, Astone, De Vita, Pozzi, Riccardi, Greco, Moscetti, Giordano, Maugeri-Saccà, Zennaro, Botti, Pelle, Cappelli, Cavicchi, Vizza, Sanguineti, Tomao, Cortesi, Marchetti, Tomao, Speranza, Sperduti, Ciliberto and Vici.)

Purpose: Anticancer treatment-related toxicities can impact morbidity and mortality, hamper the administration of treatment, worsen the quality of life and increase the burden on the healthcare system. Therefore, their prompt identification is crucial. NICSO (Italian Network for Supportive Care in Cancer) conducted a nationwide randomized trial to evaluate the role of a planned, weekly phone-based nurse monitoring intervention to prevent and treat chemotherapy, targeted therapy- and immunotherapy-related toxicities. Here, we report the results from the chemotherapy arm., Methods: This was a nationwide, randomized, open-label trial conducted among 29 Italian centers (NCT04726020) involving adult patients with breast, colon, or lung cancer and a life expectancy ≥6 months receiving adjuvant chemotherapy. Patients received either a weekly nurse monitoring phone call and an educational leaflet reporting practical advice about prevention and treatment of toxicities (experimental group) or the educational leaflet only (control group)., Results: The addition of a nurse monitoring intervention may help reduce time spent with severe toxicities (grade ≥3), particularly those less frequently reported in clinical practice, such as fatigue. When considering grade 1-2 AEs, times with mild/moderate diarrhea, mucositis, fatigue and pain were shorter in the experimental arm. Time spent without AEs was significantly longer in the experimental arms for all the toxicities. The requirement for special medical attention was comparable between groups., Conclusion: This study suggests the need for implementing a better system of toxicity assessment and management for patients treated with adjuvant chemotherapy to promote effective preventive and/or therapeutic intervention against these events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Antonuzzo, Ripamonti, Roila, Sbrana, Galli, Miccinesi, Sammarco, Berruti, Coletta, Velutti, Fabi, Corsi, Mariani, Di Pede, Spinelli, Santini, Zustovich, Gunnellini, Rossi, Giordano, Di Maio, Numico and Bossi.)

Background: Second- or third-line treatment options for metastatic renal cell carcinoma (mRCC) have dramatically changed in the last few years. There are no criteria for the choice between nivolumab and cabozantinib, which both demonstrated overall survival (OS) gain in pivotal trials., Objective: We conducted an analysis of oncological outcomes in patients treated in the Veneto Region (Italy), studying different sequences of TKI-nivolumab-cabozantinib or TKI-cabozantinib-nivolumab in a publicly funded healthcare system., Patients and Methods: We conducted a retrospective, real-world analysis of all consecutive patients with mRCC treated with nivolumab or cabozantinib in 2017-2018 at 19 Oncology Units in the Veneto Region., Results: We identified 170 patients, 73 % males, median age 68.4 years. All patients started second-line treatment, 59 % received a third-line therapy. Patients with NLR > 3 had a shorter OS (p < 0.0001). In the second-line treatment, nivolumab was administered to 108 patients (63 %), cabozantinib to 29 (17 %); in the third-line treatment nivolumab was administered to 42 patients (25 %), cabozantinib to 49 (29 %). Median OS and PFS in second line treatment were 28.4 and 6.6 months for nivolumab, 16.8 and 6.6 months for cabozantinib. Median OS and PFS in third-line treatment were 27 and 5.2 months for nivolumab, 16.6 and 7.5 months for cabozantinib. Median OS for nivolumab>cabozantinib sequence versus cabozantinib > nivolumab was 28.8 versus 19.9 months (p = 0.2); median PFS for both the sequences were similar at 5.7 months. A cost effectiveness per month of survival of the two sequences analysis was performed: the cost per month for the nivolumab > cabozantinib sequence was 1738.60whereas the cost for the other one was €1624.80., Conclusions: In our real-world cohort, most patients received nivolumab as second-line treatment. Outcomes of single drugs are superimposable with those in the published literature. Both the sequences of nivolumab and cabozantinib appear to be viable, effective strategies from an OS and cost-effective perspective., (© 2022. The Author(s).)

Background: Real-world (RW) evidence on nivolumab in pretreated patients with non-small cell lung cancer (NSCLC) by matching data from administrative health flows (AHFs) and clinical records (CRs) may close the gap between pivotal trials and clinical practice., Methods: This multicenter RW study aims at investigating median time to treatment discontinuation (mTTD), overall survival (mOS) of nivolumab in pretreated patients with NSCLC both from AHF and CR; clinical-pathological features predictive of early treatment discontinuation (etd), budget impact (BI), and cost-effectiveness analysis were investigated; mOS in patients receiving nivolumab and docetaxel was assessed., Results: Overall, 237 patients with NSCLC treated with nivolumab were identified from AHFs; mTTD and mOS were 4.2 and 9.8 months, respectively; 141 (59%) received at least 6 treatment cycles, 96 (41%) received < 6 (etd). Median overall survival in patients with and without etd were 3.3 and 19.6 months, respectively (P < .0001). Higher number, longer duration, and higher cost of hospitalizations were observed in etd cases. Clinical records were available for 162 patients treated with nivolumab (cohort 1) and 83 with docetaxel (cohort 2). Median time to treatment discontinuation was 4.8 and 2.6 months, respectively (P < .0001); risk of death was significantly higher in cohort 2 or cohort 1 with etd compared with cohort 1 without etd (P < .0001). Predictors of etd were body mass index <25, Eastern Cooperative Oncology Group performance status >1, neutrophile-to-lymphocyte ratio >2.91, and concomitant treatment with antibiotics and glucocorticoids. The incremental cost-effectiveness ratio of nivolumab was 3323.64 euros ($3757.37) in all patients and 2805.75 euros ($3171.47) for patients without etd. Finally, the BI gap (real-theoretical) was 857 188 euros ($969 050.18)., Conclusion: We defined predictors and prognostic-economic impact of nivolumab in etd patients., (© The Author(s) 2022. Published by Oxford University Press.)