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KRAS is the most frequently mutated gene in non-small cell lung cancer (NSCLC), however conflicting data are available on its role as a biomarker.The aim of our work was to investigate the impact of KRAS mutations on response and survival outcomes in advanced non-squamous NSCLC patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy.We retrospectively identified 119 patients, most of whom (58%) were KRAS wild type. For each patient we evaluated overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). An exploratory analysis was performed among KRAS mutated patients to investigate the impact of specific KRAS mutations on response and survival outcomes.After a median follow-up of 10.3 months, the median OS was 14.9 months (95% confidence interval [CI] 7.6-22.7) in wild-type KRAS patients versus 14.7 months (95% CI 8.0-19.5) in mutated KRAS patients (p = 0.529). No differences were detected between the two groups in terms of PFS and DCR. Patients with a KRAS G12C mutation reported survival and response outcomes that were not statistically different from those of patients with other KRAS mutations.Our data confirmed that KRAS mutational status is not associated with survival and response outcomes in advanced non-squamous NSCLC patients treated with immunotherapy alone or combined with chemotherapy.

PurposeTo evaluate the impact of KRAS mutations on response and survival outcomes in mutated vs wild type KRAS advanced non squamous non small cell lung cancer patients treated with immune checkpoint inhibitors alone or in combination with chemotherapy. Patients and methodsWe retrospectively identified 119 patients, most of which (58%) were wild type. For each patient we evaluated overall survival (OS), progression free survival (PFS) and disease control rate (DCR). An exploratory analysis was performed among mutated patients to investigate the impact of specific KRAS mutations on response and survival outcomes. ResultsAfter a median follow-up of 10.3 months, the median OS was 14.9 months (95% CI 7.6 – 22.7) in wild type KRAS patients vs 14.7 months (95% CI 8.0 – 19.5) in mutated KRAS patients; p-value=0.529. No differences were also detected between two groups in terms of PFS and DCR. Patients with pG12C KRAS mutation reported survival and response outcomes that were not statistically different from those of patients with other KRAS mutations. ConclusionOur data confirmed that KRAS mutational status is not associated with survival and response outcomes in advanced non squamous NSCLC patients treated with immunotherapy alone or combined to chemotherapy.

Purpose Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting. Methods We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described. Results The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%). Conclusions This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.

Pembrolizumab monotherapy has demonstrated durable antitumor activity in advanced programmed death ligand 1 (PD-L1)-expressing nonEligible patients had confirmed locally advanced/metastatic NSCLC and provided a contemporaneous tumor sample for PD-L1 evaluation by immunohistochemistry using the 22C3 antibody. Patients received intravenous pembrolizumab 2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks. Investigators assessed response per immune-related response criteria. The primary efficacy end point was objective response rate. Overall survival (OS) and duration of response were secondary end points.We enrolled 101 treatment-naive and 449 previously treated patients. Median follow-up was 60.6 months (range, 51.8 to 77.9 months). At data cutoff-November 5, 2018-450 patients (82%) had died. Median OS was 22.3 months (95% CI, 17.1 to 32.3 months) in treatment-naive patients and 10.5 months (95% CI, 8.6 to 13.2 months) in previously treated patients. Estimated 5-year OS was 23.2% for treatment-naive patients and 15.5% for previously treated patients. In patients with a PD-L1 tumor proportion score of 50% or greater, 5-year OS was 29.6% and 25.0% in treatment-naive and previously treated patients, respectively. Compared with analysis at 3 years, only three new-onset treatment-related grade 3 adverse events occurred (hypertension, glucose intolerance, and hypersensitivity reaction, all resolved). No late-onset grade 4 or 5 treatment-related adverse events occurred.Pembrolizumab monotherapy provided durable antitumor activity and high 5-year OS rates in patients with treatment-naive or previously treated advanced NSCLC. Of note, the 5-year OS rate exceeded 25% among patients with a PD-L1 tumor proportion score of 50% or greater. Pembrolizumab had a tolerable long-term safety profile with little evidence of late-onset or new toxicity.

Dysgeusia and taste alterations (TAs) are side effects of cytotoxic chemotherapy and affect patients' quality of life; however, the prevalence, types, and duration of TAs and their potential relationship with other clinical disturbances are not well-described. Our primary aim was to prospectively evaluate the characteristics of TAs in early breast cancer (EBC) patients during (neo)adjuvant chemotherapy and up to 1 year after its completion.From April 2014 to June 2018, 182 EBC patients entered the study and received (neo)adjuvant chemotherapy, mostly with taxane and anthracycline-containing regimens (65% of cases). A dietitian performed TAs assessment through the Common Terminology Criteria for Adverse Event v4.0 (CTCAE) and the Chemotherapy-induced Taste Alteration Scale (CiTAS) questionnaire during chemotherapy and follow-up according to defined time points: at baseline (T0, before starting chemotherapy); at the first follow-up visit, (T1, 2 months after starting chemotherapy); at the final follow-up visit (T2, 1 week after completing chemotherapy); after that, every 3 months up to 12 months.Dysgeusia was reported by 69.8% of patients at T1 and declined subsequently; salty flavor distortion was the most frequently reported TA (51.6% of cases). CiTAS was significantly different between T0 and T2 (p 0.001). Dysgeusia occurred more frequently in patients reporting nausea, mucositis, diarrhea, and appetite modification.TAs are common but transient during chemotherapy and occurred frequently with other distressing gastrointestinal side effects. The assessment of these side effects is crucial in managing EBC patients during (neo)adjuvant chemotherapy.

ObjectiveTo evaluate the efficacy of clinical triage of oncological patients for safe continuation of cancer therapy implemented during the first SARS-CoV-2 outbreak.MethodsBetween 25 February and 21 April 2020, patients attending the Medical Oncology Unit, Spedali Civili Hospital, Brescia (Italy) for cancer therapy underwent triage to identify those with no signs and symptoms suspicious for SARS-CoV-2 infection in which antineoplastic treatment could be continued as scheduled. Triage questions investigated common symptoms (e.g., fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhea, nausea and vomiting); body temperature and pulse oximetry were also recorded. All patients were followed-up for overt SARS-CoV-2 through to 18th May 2020.ResultsOverall, 1180 patients (median age 65 years) underwent triage during the study period. The most frequent primary malignances were breast (32%), gastrointestinal (18%), and lung (16.5%) cancer. Thirty-one (2.5%) presented with clinically evident SARS-CoV-2 infection and tested positive on nasopharyngeal swab testing and/or radiological imaging. Triage identified 69 (6%) grey zone patients with symptoms suspicious for SARS-CoV-2; 5 (7.2%) subsequently developed symptomatic disease. Neither the symptomatic nor the grey zone patients received their scheduled treatment; instead, they were referred for hospitalization or home quarantine.ConclusionTriage of oncological patients at our Unit provided for safe continuation of scheduled cancer treatment in 91.5% of patients during the initial SARS-CoV-2 outbreak.

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2–3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt “healthier dietary patterns” during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.

Background: During the SARS-COV-2 pandemic, cancer patients (pts) who are infected may develop severe disease if their systemic treatment is not temporarily stopped Nasopharyngeal swab was not extensively available to screen cancer pts for SARS-COV-2 infection in northern Italy, the most area in the country most affected by the pandemic From the beginning of the outbreak onwards, all pts admitted to the Medical Oncology Unit at Spedali Civili Hospital, Brescia, underwent a triage investigating the presence of symptoms and signs suggestive of SARS-COV-2 infection Triage results were used to decide which pts should continue antineoplastic treatments Methods: All consecutive cancer pts being admitted for systemic treatment from February 24th to April 21st 2020 were considered Triage, performed by a trained nurse, consisted of questions regarding the presence of fever, cough, dyspnea, anosmia, dysgeusia, headache, nasal congestion, conjunctival congestion, sore throat, diarrhoea, nausea and vomiting, measurement of body temperature and pulse oximetry All enrolled pts were followed-up for overt SARS-COV-2 development until May 18th Results: Overall, 1180 pts were included, 54% female and median age 65 years Most represented primary malignancies were breast (32%), gastroenteric (18%) and lung (16 5%) Thirty-one (2 5%) presented with clinically evident SARS-COV-2 disease and infection was proven by positive nasopharyngeal swab and/or radiological imaging The triage identified 69 (6%) “grey zone” pts, with suspicious symptoms (i e fever 41%, cough 30%, dyspnea 19%) The nasopharyngeal swab was negative in 48% of them and was not performed in the remaining 52% of pts, as well as in all pts who were triage negative Both SARS-COV-2 positive and “grey zone” pts did not receive treatment and were addressed to hospitalisation or home quarantine All the 1080 pts (91 5%) who resulted negative at triage continued their antineoplastic therapy as scheduled, none of them presenting symptoms of SARS-COV-2 infection during the follow-up Conclusions: Accurate triage allowed safe continuation of anticancer treatment in 91 5% of pts during the SARS-COV-2 outbreak Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Patients with cancer are at a higher risk of developing serious disease-related complications in case of contracting SARS-CoV-2. Oncology units should implement all possible preventive measures to reduce the risk of viral transmission by healthcare professionals (HCPs) to patients. We conducted a surveillance for SARS-CoV-2 infection among the staff members of the Medical Oncology Unit of ASST Spedali Civili in Brescia, one of the Italian areas most affected by the SARS-CoV-2 pandemic. The aim of this study was to demonstrate whether the recommended preventive measures, promptly implemented by the unit, have been effective in reducing the spread of the virus among the HCPs. Between February 24 and May 19, 2020, SARS-CoV-2 infection was detected in 10 out of 76 healthy HCPs (13%). Six of them developed a symptomatic disease, leading to home quarantine, and four remained asymptomatic. The infection was revealed when a serology test was performed on all staff members of the unit. In seven HCPs, in which it was possible to trace the person-to-person infection, the contagion occurred as a result of unprotected contacts or partially protected with surgical masks. In particular, four asymptomatic HCPs did not stop working, but a widespread outbreak in the unit was avoided. Adherence to the recommended preventive strategies, in particular, wearing of surgical masks by both the HCPs and the patients, is effective in reducing and preventing the viral spread.

Background Clinical-pathologic predictors of acquired T790M epidermal growth factor receptor (EGFR) mutation in Caucasian patients with non–small-cell lung cancer (NSCLC) progressing after first-/second-generation tyrosine kinase inhibitors (TKIs) is an open field for research. Similarly, the best time point for T790M detection by liquid or tissue biopsy after disease progression is currently matter of debate. Patients and Methods This is an observational study at 7 Italian centers enrolling patients with EGFR-mutant NSCLC progressing after first-/second-generation EGFR TKIs, between 2014 and 2018, aiming at comparing baseline clinical-pathologic features and progression patterns in acquired T790M-positive compared with T790M-negative cases. Results A total of 235 patients received first-line treatment with gefitinib (N = 126; 53%), erlotinib (N = 51; 22%), or afatinib (N = 58; 25%). In 120 (51%) cases, T790M was detected in liquid biopsy, tissue biopsy, or both. Age younger than 65 years (P = .037), the presence of common mutations (P = .004), and better response to first-line TKI (P = .023) were correlated with T790M positivity. T790M detection was associated with higher number of new progressing sites (P = .04), liver progression (P = .002), and a lower frequency of lung metastases (P = .027). When serial liquid biopsies were performed (N = 15), an oligoprogressive disease was correlated with a negative test outcome, whereas systemic progression was observed at the time of T790M positivity. Conclusion This study on a Caucasian population showed that age, type of EGFR mutation at diagnosis, response to first-line treatment, and peculiar progression pattern are associated with T790M status. Serial liquid biopsy might be useful for treatment selection, especially when tissue rebiopsy is not feasible.

Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High‐fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI‐naïve or AI‐treated. A total of 684 consecutive breast cancer patients were enrolled in this cross‐sectional study. Each woman underwent a dual‐energy X‐ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI‐naïve and 240 AI‐treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI‐treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high‐LBM and low‐FBM group, 23.2% in high‐LBM and high‐FBM group, and 19.8% in low‐LBM and low‐FBM group). Among AI‐naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Breast cancer represents the most frequent cancer among women in Western countries. Although physicians and patients have witnessed a significant evolution in both treatment strategies and personalized medicine (the identification of featured patients' subsets such as HER2-driven disease), the identification of additional prognostic clinical predictors referring to patients' dietary habits represents a research area aiming to further improve the overall management of this disease. In this regard, body composition (i.e. the relative proportion of fat and muscles) and its changes have recently generated growing interest. A large body of evidence supports the relationship between overweight or weight gain and poor outcome in patients with early-stage breast cancer during adjuvant, and more recently, also neoadjuvant therapy. Nevertheless, available data on post-diagnosis weight variations and mortality report controversial results. Indeed, the limited data produced in the metastatic setting do not indicate an impact of body size on the outcome of these patients. With these perspectives, this review aims to elucidate the complex association between weight, body composition and breast cancer outcome, across the different settings of such disease. The more recent and important findings are highlighted, emphasizing the potential role of body composition assessment to predict individualize chemotherapy dosing, toxicity and efficacy, in order to improve the overall health status and prognosis of such still to date growing patients' population.

Aim: With the final aim to explore the first-line treatment options for non-small-cell lung cancer (NSCLC) patients, we performed a systematic review and literature-based meta-analysis of available clinical trials exploring immunotherapy in combination versus standard histology-based chemotherapy. Materials & methods: We evaluated interactions according to type of treatment-add-on strategy: immunotherapy in combination versus standard chemotherapy-based regimens. Hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were extracted and cumulated. Results: Seven trials (4278 patients) were included. The addition of immunotherapy to standard chemotherapy-based regimens significantly increased OS (HR 0.74; p = 0.001) and PFS (HR 0.61; p

e20612 Background: Acquired T790M EGFR mutation (mut) is not predictable by any clinical-pathological feature. The best time point for T790M mut detection by liquid or tissue biopsy is currently undefined. Methods: This is an observational study at 6 Italian Centers enrolling EGFR mutant NSCLC patients (pts) progressing after first/second generation EGFR TKI, between 2014 and 2018. The primary endpoint of the study was to compare clinical features in acquired T790M+ compared with T790M- cases. The secondary endpoint was to assess different progression (PD) patterns between the two groups. We also explored the PD pattern at the time of cfDNA negativity and subsequent positivity, in a subgroup of pts receiving serial liquid biopsies. Statistical analysis was performed by the Chi-square test to correlate clinical features with T790M status, and by the Kaplan-Meier estimator to evaluate median progression free (mPFS) and overall survival (mOS). Multiple logistic regression and log-rank tests were applied. Results: 219 pts were included. Median follow-up since diagnosis was 25 months. First line treatment was gefitinib (N = 119, 54%), erlotinib (N = 48, 22%) or afatinib (N = 52, 24%). In 108 (49%) cases a T790M acquired mut was detected in liquid (70), tissue (31) biopsy or both (7). Age younger than 65 years ( p= 0.05) and presence of sensitizing exon 19 deletion ( p= 0.04) were correlated with T790M mut; this association was confirmed at multivariate analysis ( p= 0.010 and p= 0.006, respectively). At the time of PD, new PD sites ( p= 0.005) and liver PD ( p< 0.001) were more commonly observed in T790M+ group; at multivariate analysis statistical significance was confirmed ( p= 0.01 and p= 0.008, respectively). Longer mOS was observed in T790M+ cases at univariate (53 versus 22 months, p < 0.0001) and multivariate analysis. In 13 pts undergoing serial liquid biopsies, an oligoprogressive disease was correlated with a negative test outcome, while PS/symptoms worsening, higher number of new lesions and PD sites were observed at the time of T790M positivity, although without statistical significance. Conclusions: This is the first caucasian series showing different clinical features and progression patterns of T790M+ versus T790M- EGFR mutant NSCLC.

e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not...