Implementation of Precision Oncology in Clinical Practice: Results of a National Survey for Health Care Professionals.

BACKGROUND: Two main aspects lead the implementation of precision oncology into clinical practice: the adoption of extended genome sequencing technologies and the institution of the Molecular Tumor Boards (MTBs). CIPOMO (Italian Association of Heads of Oncology Department) promoted a national survey across top health care professionals to gain an understanding of the current state of precision oncology in Italy. METHODS: Nineteen questions were sent via the SurveyMonkey platform to 169 heads of oncology departments. Their answers were collected in February 2022. RESULTS: Overall, 129 directors participated; 113 sets of answers were analyzed. Nineteen regions out of 21 participated as a representative sample of the Italian health care system. The use of next-generation sequencing (NGS) is unevenly distributed; informed consent and clinical reports are managed differently, as the integration of medical, biologic, and informatics domains in a patient-centered workflow is inconsistent. A heterogeneous MTB environment emerged. A total of 33.6% of the responding professionals did not have access to MTBs while 76% of those who have did not refer cases. CONCLUSIONS: NGS technologies and MTBs are not homogeneously implemented in Italy. This fact potentially jeopardizes equal access chances to innovative therapies for patients. This survey was carried out as part of an organizational research project, pursuing a bottom-up approach to identify the needs and possible solutions to optimize the process. These results could be a starting point for clinicians, scientific societies, and health care institutions to outline the best practices and offer shared recommendations for precision oncology implementation in current clinical practice.

Non-small cell lung cancer harboring EGFR G724S mutation and exon 19 deletion responded to afatinib monotherapy after multiple lines of target therapies.

Epidermal growth factor receptor (EGFR) G724S mutation represents a resistance mechanism to first- and third-generation EGFR tyrosine kinase inhibitors. Limited data are available regarding the efficacy of afatinib in patients with non-small cell lung cancer (NSCLC) harboring G724S mutation, particularly after osimertinib. A patient diagnosed with advanced EGFR-mutated (exon 19 deletion) NSCLC after several lines of treatment - gefitinib, osimertinib, heat shock protein inhibitors and chemotherapy-developed EGFR G724S mutation retaining the exon 19 deletion. She was then treated successfully with afatinib leading to a progression free survival of 9 months (and counting). This is the first report of the emergence of G724S mutation, together with ex19del, after three subsequent lines of therapy following progressive disease to Osimertinib, and we report for the first time the activity of afatinib against EGFR exon 18 G724S mutation in this setting.

Immunotherapy in NSCLC Patients with Brain Metastases.

Approximately 40% of unselected non-small cell lung cancer (NSCLC) patients develop brain metastases (BMs) during their disease, with considerable morbidity and mortality. The management of BMs in patients with NSCLC is a clinical challenge and requires a multidisciplinary approach to gain effective intracranial disease control. Over the last decade, immune checkpoint inhibitors (ICIs) have emerged as a game-changer in the treatment landscape of advanced NSCLC, with significant improvements in survival outcomes, although patients with BMs are mostly underrepresented in randomized clinical trials. Moreover, the safety and activity of ICIs and radiotherapy combinations compared with single-agent or sequential modalities is still under evaluation to establish the optimal management of these patients. The aim of this review is to summarize the state-of-the-art of clinical evidence of ICIs intracranial activity and the main challenges of incorporating these agents in the treatment armamentarium of NSCLC patients with BMs.

Feasibility and Predictive Performance of a Triage System for Patients with Cancer During the COVID-19 Pandemic.

BACKGROUND: Triage procedures have been implemented to limit hospital access and minimize infection risk among patients with cancer during the coronavirus disease (COVID-19) outbreak. In the absence of prospective evidence, we aimed to evaluate the predictive performance of a triage system in the oncological setting. MATERIALS AND METHODS: This retrospective cohort study analyzes hospital admissions to the oncology and hematology department of Udine, Italy, during the COVID-19 pandemic (March 30 to April 30, 2020). A total of 3,923 triage procedures were performed, and data of 1,363 individual patients were reviewed. RESULTS: A self-report triage questionnaire identified 6% of triage-positive procedures, with a sensitivity of 66.7% (95% confidence interval [CI], 43.0%-85.4%), a specificity of 94.3% (95% CI, 93.5%-95.0%), and a positive predictive value of 5.9% (95% CI, 4.3%-8.0%) for the identification of patients who were not admitted to the hospital after medical review. Patients with thoracic cancer (odds ratio [OR], 1.69; 95% CI, 1.13-2.53, p = .01), younger age (OR, 1.52; 95% CI, 1.15-2.01, p < .01), and body temperature at admission ≥37°C (OR, 9.52; 95% CI, 5.44-16.6, p < .0001) had increased risk of positive triage. Direct hospital access was warranted to 93.5% of cases, a further 6% was accepted after medical evaluation, whereas 0.5% was refused at admission. CONCLUSION: A self-report questionnaire has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. Differential diagnosis with tumor- or treatment-related symptoms is always required to avoid unnecessary treatment delays. Body temperature measurement improves the triage process's overall sensitivity, and widespread SARS-CoV-2 testing should be implemented to identify asymptomatic carriers. IMPLICATIONS FOR PRACTICE: This is the first study to provide data on the predictive performance of a triage system in the oncological setting during the coronavirus disease outbreak. A questionnaire-based triage has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms, and a differential diagnosis with tumor- or treatment-related symptoms is mandatory to avoid unnecessary treatment delays. Consequently, adequate recourses should be reallocated for a triage implementation in the oncological setting. Of note, body temperature measurement improves the overall sensitivity of the triage process, and widespread testing for SARS-CoV-2 infection should be implemented to identify asymptomatic carriers.

The MIMIC Study: Prognostic Role and Cutoff Definition of Monocyte-to-Lymphocyte Ratio and Lactate Dehydrogenase Levels in Metastatic Colorectal Cancer.

BACKGROUND: Monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels are circulating biomarkers that provide information about tumor-related inflammation and immune suppression. This study aimed to evaluate the prognostic role of MLR and LDH in metastatic colorectal cancer (mCRC). MATERIAL AND METHODS: This multicentric study analyzed a consecutive cohort of 528 patients with mCRC treated in 2009-2017. The whole population was randomly divided in training and validation cohort. The first was used to identify a threshold for MLR and to create the prognostic model with MLR and MLR-LDH combined (group 1: MLR-LDH low; group 2: MLR or LDH high; group 3: MLR-LDH high). The second cohort was used to validate the model. RESULTS: At the median follow-up of 55 months, median overall survival (OS) was 22 months. By multivariate analysis, high MLR >0.49 (hazard ratio [HR], 2.37; 95% confidence interval [C.I.], 1.39-4.04), high LDH (HR, 1.73; 95% C.I., 1.03-2.90) in the first model, group 2 (HR, 2.74; 95% C.I.; 1.62-4.66), and group 3 (HR, 3.73; 95% C.I., 1.94-7.18) in the combined model, had a worse prognosis in terms of OS. These data were confirmed both in the validation set and then in the whole cohort. CONCLUSION: MLR and LDH are circulating cost-effective biomarkers, readily available in clinical practice, that can be useful for predicting the prognosis of patients with mCRC. IMPLICATIONS FOR PRACTICE: High monocyte-to-lymphocyte ratio (MLR) and lactate dehydrogenase (LDH) levels could be a sign of a tumor's recruitment of suppressive and inflammatory cells worsening prognosis of different types of cancer, including colorectal cancer (CRC). Currently, no data are available for metastatic CRC regarding a cutoff definition for MLR or the prognostic impact of MLR and MLR-LDH combined. The present study showed in the training cohort and confirmed in the validation and whole cohort that MLR is a reliable and independent laboratory biomarker, which is easy to use, to predict clinical outcomes in patients with mCRC. Moreover, MLR and composite MLR-LDH could potentially result in an incremental improvement in the prognostic value of these biomarkers, being used as stratification tools for patients with mCRC.

Determinants of choice in offering drug holidays during first-line therapy for metastatic colorectal cancer.

Background: 'Drug holidays' (DH) for metastatic colorectal cancer (mCRC) were introduced to preserve quality of life. We studied factors associated to a DH offer in first line. Materials & methods: We retrospectively analyzed 754 consecutive patients treated with chemotherapy for mCRC in two Italian institutions between 2005 and 2017. Associations between baseline clinical-pathological factors and DH (56 or more days of treatment interruption) were investigated. Results: In 754 patients, previous metastasectomy, previous thermoablation and previous surgery of primary tumor were independently associated with DH. Excluding procedures or clinical trials: primary rectal cancer and resection of primary tumor were significantly associated to DH. Conclusions: DH was offered to patients with lower burden of disease, but further investigations are needed to safely guide a holiday strategy.

Clinico-radiological monitoring strategies in patients with metastatic breast cancer: a real-world study.

Aim: A monitoring strategy for metastatic breast cancer patients (M-MBC) has been little studied. Materials & methods: This retrospective study analyzed a consecutive cohort of 382 MBC patients to analyze different M-MBC strategies to identify factors influencing intensive M-MBC. Results: Elevated baseline serum tumor markers (STM) was the strongest factor associated with increased use of STM tests. Having more frequent oncology office visits was associated with more intensive chemotherapy/magnetic resonance imaging (MRI) using. Increased use of imaging tests was associated with participation to clinical trial. Single and elderly patients were less likely to have frequent testing. Having clinically measurable disease was less likely to have more intensive M-MBC. Conclusion: STM testing and scans were frequently ordered in M-MBC. In the present study, strategies are little influenced by clinico-pathological characteristics.

Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

INTRODUCTION: Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering BRCA genes status. METHODS: We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to BRCA genes status as follows: all comers (AC) population, BRCA 1/2 mutated (BRCAm), and BRCA wild type patients (BRCAwt). RESULTS: In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54-0.91). In the BRCA mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36-0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63-1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively). CONCLUSIONS: PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.

Platinum Salts in Patients with Breast Cancer: A Focus on Predictive Factors.

Breast cancer (BC) is the most frequent oncologic cause of death among women and the improvement of its treatments is compelling. Platinum salts (e.g., carboplatin, cisplatin, and oxaliplatin) are old drugs still used to treat BC, especially the triple-negative subgroup. However, only a subset of patients see a concrete benefit from these drugs, raising the question of how to select them properly. Therefore, predictive biomarkers for platinum salts in BC still represent an unmet clinical need. Here, we review clinical and preclinical works in order to summarize the current evidence about predictive or putative platinum salt biomarkers in BC. The association between BRCA1/2 gene mutations and platinum sensitivity has been largely described. However, beyond the mutations of these two genes, several other proteins belonging to the homologous recombination pathways have been linked to platinum response, defining the concept of BRCAness. Several works, here reviewed, have tried to capture BRCAness through different strategies, such as homologous recombination deficiency (HRD) score and genetic signatures. Moreover, p53 and its family members (p63 and p73) might also be used as predictors of platinum response. Finally, we describe the mounting preclinical evidence regarding base excision repair deficiency as a possible new platinum biomarker.

An Italian Delphi study to evaluate consensus on adjuvant endocrine therapy in premenopausal patients with breast cancer: the ERA project.

BACKGROUND: Several trials evaluated the role of ovarian function suppression for the adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer. Based on the results of the SOFT and TEXT trials, international guidelines recommend the addition of ovarian function suppression to standard adjuvant endocrine therapy for patients at higher risk of relapse. METHODS: The ERA project (Evaluation of Risk factors in the Adjuvant treatment of breast cancer in premenopausal patients) was devised with the objective of obtaining a consensus on the identification of risk factors and the use of ovarian function suppression in the adjuvant treatment of these women. To this aim, a panel of 31 Italian oncologists with expertise in breast cancer participated in a Delphi consensus study in June 2017. RESULTS: A total of 29 statements related to prognostic factors, therapeutic strategies and ovarian function suppression were defined and voted to gain final consensus. For each topic we report data supporting the acquired consensus and the relevant issues discussed. CONCLUSIONS: The SOFT and TEXT trials have changed the standard adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer, but the available treatment options require a careful risk assessment and toxicities evaluation to ensure the greatest clinical benefit for each patient.

Comparison of primary breast cancer and paired metastases: biomarkers discordance influence on outcome and therapy.

AIM: Discordance between primary tumor and paired metastases biology has been widely detected in metastatic breast cancer. The aim of this study was to evaluate the prognostic impact of Ki67, estrogen receptor (ER), progesterone receptor (PR) and HER2 discordance. METHODS: We retrospectively analyzed a cohort of 544 patients affected by metastatic breast cancer. Variation in ER, PR, Ki67 and HER2 expression between primary site and recurrence was tested through the McNemar test. RESULTS: A significant variation was observed in respect to ER, PR and Ki67 status (12.65%, p = 0.0072; 49.71%, p < 0.0001; 35%, p < 0.0001, respectively). Among patients with ER or PR discordance, the driver of therapeutic decisions was the ER status. Moreover, we observed a therapy-related reduction of ER in taxanes or aromatase inhibitors-exposed patients (odds ratio: 3.59; 95% CI: 1.66-7.77; p = 0.001 and odds ratio: 2.07; 95% CI: 0.96-4.44; p = 0.06, respectively). CONCLUSION: Biopsy of metastatic lesions may influence the decision-making process translating into better outcome.

Sotorasib in KRASp.G12C mutated advanced NSCLC: Real-world data from the Italian expanded access program.

BACKGROUND: Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRASp.G12C-mutated advanced non-small-cell lung cancer (NSCLC) within the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP). METHODS: Sotorasib (960 mg, orally, once daily) was available on physician request for KRASp.G12C mutant advanced NSCLC patients. Clinical-pathological and molecular data were collected from the Italian ATLAS real-world registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed. RESULTS: A total of 196 advanced NSCLC patients were treated across 30 Italian centers. Median age was 69 years old (range 33-86). Most patients were male (61 %), former (49 %) or current smokers (43 %), with ECOG-PS 0/1 (84 %) and adenocarcinoma subtype (90 %). 45 % and 32 % of patients received sotorasib in 2nd and 3rd line, respectively. Overall, response rate was 26 % and the median duration of response was 5.7 months (95 % CI: 4.4-7.0). Median PFS and OS were 5.8 months (95 % CI: 5 - 6.5) and 8.2 months (95 % CI: 6.3 - 9.9). Grade 3-4 TRAEs occurred in 16.5 % of patients, with Grade ≥ 3 liver enzyme increase and TRAEs-related discontinuation reported in 12 % and 4.6 % of cases. CONCLUSION: Real-world data from the Italian EAP confirm the tolerability and effectiveness of sotorasib in patients with KRASp.G12C-mutated advanced NSCLC and highlight the value of the national ATLAS network as source of real-world evidence driving the clinical management of NSCLC patients.

Estimating survival in patients with melanoma brain metastases: prognostic value of lactate dehydrogenase.

Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM. In this study, 150 consecutive patients with MBM were retrospectively analyzed with the aim of evaluating independent prognostic factors for MBM patients, including LDH. Furthermore, we implemented a disease-specific prognostic score and estimated survival according to treatment modalities. On the basis of multivariable Cox regression analyses, six prognostic factors (age, BRAF status, number of MBM, number of extracranial metastatic sites, performance status, and LDH level) resulted statistically significant in terms of survival and were combined in a prognostic score to stratify patients in distinct prognostic groups ( P  < 0.0001). Among treatment modalities, a multimodal approach with stereotactic radiosurgery or neurosurgery associated with systemic therapy showed the best outcome (median overall survival: 12.32 months, 95% confidence interval, 7.92-25.30). This is the first study to demonstrate that LDH has independent prognostic value for patients with MBM and might be used to improve prognostic stratification, albeit external validation is mandatory. Survival of patients with MBM is affected by both disease-specific risk factors and treatment modalities, with locoregional treatments associated with better outcomes.

Immunotherapy for older patients with melanoma: From darkness to light?

Approximately 40% of malignant melanomas are diagnosed in patients older than 65 years. Elderly patients with melanoma present clinicopathological features related to a more aggressive biology, and they are often diagnosed with advanced stage of disease. Interestingly, in older patients the immune system can be altered with changes both in the innate system and in the adaptive immune system with the acquisition of a pro-inflammatory and immune suppressive phenotype. Immunotherapy with immune checkpoint inhibitors has reshaped the treatment strategies and prognosis of patients with melanoma, and particularly, older age should not be considered a contraindication for immunotherapy. However, data regarding efficacy and safety of immunotherapy in elderly population are still limited because frail older patients are generally excluded from clinical trials. Recently, real-world data have shed light on similar efficacy and safety of immunotherapy in older population compared with younger counterpart. The aim of the present review was to summarize the available knowledge on the underlying immune system in older patients with a diagnosis of melanoma and the immunotherapeutic approaches in this population.

A new dried blood spot LC-MS/MS method for therapeutic drug monitoring of palbociclib, ribociclib, and letrozole in patients with cancer.

Therapeutic drug monitoring (TDM) is strongly suggested to define the proper drug dosage to overcome inter- and intra-patient variability in drug exposure, which is typically observed with oral anticancer agents, such as palbociclib (PALBO), ribociclib (RIBO) and letrozole (LETRO), all approved for the treatment of HR+, HER2- locally advanced or metastatic breast cancer (BC). Optimal TDM implementation requires a blood sampling organization that can be hampered by limited availability of health and laboratory personnel. Dried Blood Spot (DBS) sampling is proposed to overcome such limitations. The aim of this work was the development of a new LC-MS/MS method to analyze DBS samples containing PALBO, RIBO, and LETRO. Analytes extraction from DBS was performed by adding a methanolic solution containing the corresponding internal standards. LC-MS/MS analysis was performed using a LC Nexera (Shimadzu) system coupled with an API 4000 QTrap (SCIEX) mass spectrometer. The chromatographic separation was performed on a Luna Omega Polar C18 column (Phenomenex). The method was applied to 38 clinical samples collected by finger prick. The influence of hematocrit and spot size, sample homogeneity, stability, and correlation between finger prick and venous DBS measurement were assessed. The analytical validation was performed according to EMA and FDA guidelines. The analytical range of the method was 1 to 250 ng/mL for PALBO, 40 to 10000 ng/mL for RIBO, and 2 to 500 ng/mL for LETRO, where linearity was assessed, obtaining mean coefficients of determination (R2) of 0.9979 for PALBO, 0.9980 for RIBO, and 0.9987 for LETRO). The LC-MS/MS method runtime was 6.6 min. Incurred sample reanalysis demonstrated reproducibility, as the percentage difference between the two quantifications was lower than 20% for 100% of PALBO, 81.8% of RIBO, and 90.9% of LETRO paired samples. Intra- and inter-day precision (CV (%)) was lower than 11.4% and intra- and inter-day accuracy was between 90.0 and 106.5%. DBS sample stability at room temperature was confirmed for 2.5 months. A positive correlation was observed between DBS and plasma concentrations for the 3 drugs, Lin's concordance correlation coefficients obtained by DBS normalization applying a selected strategy were 0.958 for PALBO, 0.957 for RIBO, and 0.963 for LETRO. In conclusion, a fast, easy, and reproducible DBS LC-MS/MS method for the simultaneous quantification of palbociclib; ribociclib and letrozole was developed to be used in clinical practice.

Acquired EGFR C797G Mutation Detected by Liquid Biopsy as Resistance Mechanism After Treatment With Osimertinib: A Case Report.

BACKGROUND: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor approved for the treatment of T790M-positive non-small-cell lung cancer. More recently, osimertinib demonstrated improved disease control compared to other EGFR-TKIs. Multiple mechanisms of resistance have been described in T790M-positive patients who experienced treatment failure with osimertinib. CASE REPORT: We report the case of a 78-year-old non-smoker woman with stage IV EGFR L858R-positive lung adenocarcinoma presented with T790M mutation after five years of treatment with gefitinib. The patient was started on osimertinib, but after two and a half years of treatment experienced disease progression. The analyses of circulating tumor DNA using next-generation sequencing showed, together with the pre-existing T790M and exon 21 L858R, the presence of the EGFR C797G resistance mutation. CONCLUSION: Our case report revealed a rare EGFR-dependent acquired resistance mutation to osimertinib in circulating tumor DNA. Liquid biopsy appears to be a promising resource to understand the biology of osimertinib resistance by clonal evolution monitoring and the identification of novel resistance mechanisms.

Prognostic role of visceral fat for overall survival in metastatic colorectal cancer: A pilot study.

BACKGROUND: Body composition, has been established as a risk factor for colorectal cancer diagnosis and disease progression. Aim of this study was to investigate the prognostic role of adiposity, especially visceral fat (VAT), in patients (pts) with metastatic colorectal cancer (MCRC). MATERIAL AND METHODS: A retrospective cohort of 71 MCRC pts treated between 2013 and 2017 was evaluated. VAT was measured as cross-sectional (cm2) area at the L3 level divided by the square of the height (m2). A ROC analysis was performed to define a prognostic threshold according to VAT. RESULTS: Before first-line therapy start, 40 pts (56%) had a body mass index (BMI) > 25 kg/m2. The obtained cut-off value for VAT was 44. Median OS was 30.97 months. At univariate analysis, primary tumor resection (HR 0.40, p = 0.029), VAT>44 (HR 2.85, p = 0.011) and metastasectomy (HR 0.22, p = 0.005) were significantly associated with OS. By multivariate analysis, VAT>44 (HR 2.6; p = 0.020) and metastasectomy were still significantly associated with OS. CONCLUSION: This exploratory study suggests a prognostic role for VAT in MCRC pts, with higher VAT values predicting worse outcome.

Drug Holidays and Overall Survival of Patients with Metastatic Colorectal Cancer.

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22-2.32; p = 0.002 and HR,4.89; 95% CI, 3.33-7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer.

First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: A real-world study.

BACKGROUND: Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. MATERIALS AND METHODS: 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. RESULTS: At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. CONCLUSION: Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines.

Platinum-Based Chemotherapy in Older Patients with Non-Small Cell Lung Cancer: What to Expect in the Real World.

BACKGROUND: The role of platinum-based chemotherapy (PBC) for the treatment of older patients with non-small cell lung cancer (NSCLC) is still a matter of debate, despite the advent of immunotherapy. OBJECTIVE: The aim of the study was to identify factors associated with first-line PBC prescription and, secondly, to evaluate the impact of first-line PBC on survival, treatment intensity, risk of hospitalization, and subsequent treatments. PATIENTS AND METHODS: We reviewed a consecutive series of 474 older patients (age ≥ 70 years) diagnosed with stage IIIB-IV NSCLC at the Department of Oncology, University Hospital of Udine, Italy from January 2009 to March 2017. RESULTS: Overall, 198 patients were deemed eligible, and 65.2% received a PBC. At multivariate analysis, older age was the only factor associated with PBC prescription. In the whole cohort, 46 patients (23.2%) were hospitalized for chemotherapy-related toxicity. Both PBC prescription (odds ratio [OR] 2.23, 95% confidence interval [CI] 1.02-4.87, p = 0.04) and tumor burden (OR 2.39, 95% CI 1.07-5.32, p = 0.03) emerged as independent risk factors for hospitalization. Moving to significant predictors of patterns of care, Eastern Cooperative Oncology Group (ECOG) performance status > 0 was associated with greater risk of first-line failure (OR 2.20, 95% CI 1.15-4.20, p = 0.02), while bone metastases (OR 0.29, 95% CI 0.12-0.69, p = 0.005) and a Charlson Comorbidity Index score ≥ 3 (OR 0.40, 95% CI 0.19-0.84, p = 0.016) independently predicted lower probability of receiving second-line therapy. Remarkably, PBC did not significantly impact overall survival (hazard ratio [HR] 0.83, 95% CI 0.61-1.14, p = 0.24) and progression-free survival (HR 0.95, 95% CI 0.70-1.28, p = 0.73) compared to single-agent chemotherapy (SAC). However, according to an exploratory landmark analysis, patients who received four cycles of treatment or maintenance therapy experienced prolonged overall survival, regardless of PBC use. CONCLUSIONS: This study evaluated the real-world use of PBC in older patients with NSCLC, offering an insight into the determinants of its prescription and the pattern of care of these patients. Of note, PBC use was associated with a higher likelihood of hospitalization for chemotherapy-related toxicity, with no benefit on survival compared to SAC.