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BACKGROUND: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS: The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS: Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.
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Vacina BNT162 , COVID-19 , Humanos , Masculino , Idoso , Inibidores de Checkpoint Imunológico , Antígeno B7-H1 , SARS-CoV-2 , COVID-19/prevenção & controle , Recidiva Local de Neoplasia , RNA MensageiroRESUMO
We evaluated immune cell frequencies in peripheral blood samples of 41 NSCLC patients before and after second-line therapy with anti-PD-1/PD-L1 agents. Changes in lymphocyte subsets and their correlation with clinical response, progression-free survival (PFS), and overall survival (OS) were analyzed. We observed an increase in median values of all lymphocyte subsets, being significant only for NK cells. A correlation was retrieved between higher post-treatment NK cell level and clinical benefit. On multivariate analysis, PD-L1 tumor proportion score ≥1% and higher post-treatment NK cell counts were predictive of longer PFS and OS. Co-presence of these factors was characterized by longer survival.
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Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Células Matadoras Naturais , Neoplasias Pulmonares/patologiaRESUMO
Extramammary Paget's disease is a rare skin cancer that usually arises from the secretory cells of the apocrine glands. In most cases, an extramammary Paget's tumor occurs as a single intraepithelial form not associated with another cancer, although rarely, it may be associated with other loco-regional or distant cancer. It is generally slow-growing and diagnosed in situ. Most often, surgical excision with wide margins is curative, with the local recurrence rate being lower after the Mohs micrographic surgery technique. Nonetheless, relapses are frequent. In the metastatic setting, there are no treatment guidelines or standard therapies; additionally, the experience is limited to a few individual cases, and the efficacy of conventional chemotherapies is not well-defined. Moreover, chemotherapy can also have serious side effects; therefore, there is a need to identify more effective and less toxic therapies. In this case report, we have observed a long-lasting complete response with anti-HER2 plus paclitaxel.
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In advanced cancer patients undergoing immune checkpoint blockade, the burden of immune-related adverse events (irAEs) is high. The need for reliable biomarkers for irAEs remains unfulfilled in this expanding therapeutic field. The lung immune prognostic index (LIPI) is a noninvasive measure of systemic inflammation that has consistently shown a correlation with survival in various cancer types when assessed at baseline. This study sought to determine whether early changes in the LIPI score could discriminate the risk of irAEs and different survival outcomes in advanced non-small cell lung cancer (NSCLC) patients receiving PD-(L)1 blockade-based therapies. We included consecutive patients diagnosed with metastatic NSCLC who received pembrolizumab, nivolumab, or atezolizumab as second-line therapy following platinum-based chemotherapy, or first-line pembrolizumab either alone or in combination with platinum-based chemotherapy. The LIPI score relied on the combined values of derived neutrophil/lymphocyte ratio (dNLR) and lactate dehydrogenase. Their assessment at baseline and after two cycles of treatment allowed us to categorize the population into three subgroups with good (LIPI-0), intermediate (LIPI-1), and poor (LIPI-2) prognosis. Between April 2016 and May 2023, we enrolled a total of 345 eligible patients, 165 (47.8%) and 180 (52.2%) of whom were treated as first- and second-line at our facility, respectively. After applying propensity score matching, we considered 83 relevant patients in each cohort with a homogeneous distribution of all characteristics across the baseline LIPI subgroups. There was a noticeable change in the distribution of LIPI categories due to a significant decrease in dNLR values during treatment. Although no patients shifted to a worse prognosis category, 20 (24.1%) transitioned from LIPI-1 to LIPI-0, and 7 (8.4%) moved from LIPI-2 to LIPI-1 (p < 0.001). Throughout a median observation period of 7.3 (IQR 3.9-15.1) months, a total of 158 irAEs (63.5%) were documented, with 121 (48.6%) and 39 (15.7%) patients experiencing mild to moderate and severe adverse events, respectively. Multivariate logistic regression analysis showed that the classification and changes in the LIPI score while on treatment were independent predictors of irAEs. The LIPI-0 group was found to have significantly increased odds of experiencing irAEs. Following a median follow-up period of 21.1 (95% CI 17.9-25.8) months, the multivariable Cox model confirmed LIPI categorization at any given time point as a significant covariate with influence on overall survival, irrespective of the treatment line. These findings suggest that reassessing the LIPI score after two cycles of treatment could help pinpoint patients particularly prone to immune-related toxicities. Those who maintain a good LIPI score or move from the intermediate to good category would be more likely to develop irAEs. The continuous assessment of LIPI provides prognostic insights and could be useful for predicting the benefit of PD-(L)1 checkpoint inhibitors.
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Several concerns have been raised about a causal relationship between COVID-19 mRNA-based vaccines and the development of herpes zoster (HZ). We performed a prospective analysis of the Vax-On-Third-Profile study to investigate the incidence of HZ after the third dose of mRNA-BNT162b2 (tozinameran) and its correlation with immune responses. Patients who had received a booster dose and had been actively treated for at least 8 weeks were eligible. Serologic assessment was performed before the third dose of tozinameran (timepoint-1) and 4 weeks later (timepoint-2). We also assessed the incidence of SARS-CoV-2 breakthrough infections at predefined time points. The current analysis included 310 patients, of whom 109 (35.2%) and 111 (35.8%) were being treated with targeted therapies and cytotoxic chemotherapy, respectively. All participants received a third dose of tozinameran between September 26 and October 30, 2021. After a mean follow-up of 17.3 (IQR 15.1-18.4) months, HZ occurred in 8 recipients, for a cumulative incidence of 2.6%, and an incidence rate of 0.310 per person-year (95% CI 0.267-0.333). All HZ cases occurred within 30 days of booster dosing (range 5-29 days), with a median time to onset of 15 (IQR 9-22) days. Among the 7 patients (2.2%) who also contracted a SARS-CoV-2 infection, all cases preceded COVID-19 outbreaks. No instances of complicated HZ were reported. In multivariate analysis, impaired T helper and T cytotoxic cell counts independently correlated with HZ occurrence. These findings provide the first evidence that cancer patients on active treatment have a not negligible risk of developing HZ within 30 days after the third dose of tozinameran. The favorable clinical outcome of all observed cases confirms that protective effects of boosters in reducing the risk of severe COVID-19 outweigh the potential risk of HZ occurrence.
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COVID-19 , Herpes Zoster , Neoplasias , Humanos , Vacina BNT162 , Estudos Prospectivos , SARS-CoV-2 , COVID-19/prevenção & controle , Herpes Zoster/prevenção & controle , RNA MensageiroRESUMO
The addition of bevacizumab to standard chemotherapy has improved progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in both first- and second line treatment, but the role of maintenance bevacizumab remains controversial. The association of various clinical factor and survival was examined in this retrospective cohort analysis. The clinical data from 220 previously untreated patients with mCRC, not progressive at the end of standard chemotherapy plus bevacizumab, were collected and analyzed. Patients were classified into two subgroups: those given with maintenance bevacizumab: "maintenance bevacizumab cohort (n = 118; MB)", and those discontinuing bevacizumab as a result of physician's or patient's decision: "no maintenance bevacizumab cohort (n = 102; noMB)". The baseline factors were well balanced between the study subgroups. Median PFS and OS for the general population was 10 months (range 7-15) and 22.5 months (range 18-26), respectively. Median PFS was 13 and 8 months in the BM and noBM cohorts, respectively (p < 0.0001). In the multivariate analysis, maintenance therapy resulted independently associated with improved PFS (HR 1.73; p < 0.001), but only objective response (OR) after first-line chemotherapy was associated with improved OS. Maintenance chemotherapy cannot be considered a standard of care after induction chemotherapy for mCRC, because the optimal balance between efficacy and safety of maintenance therapy remains a significant challenge. The results of our retrospective study suggest that maintenance therapy with bevacizumab is a safe and valuable option, particularly in those patients achieving an objective response after first-line chemotherapy.
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Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: We evaluated the efficacy of gemcitabine and carboplatin for patients affected by pretreated metastatic breast cancer. A subgroup analysis was performed to evaluate the predictive value of immunohistochemically defined breast cancer subtypes. METHODS: We included human epidermal growth factor 2 (HER-2) negative metastatic breast cancer resistant to previous anthracycline-based and taxane-based chemotherapy, and HER-2 positive metastatic breast cancer with at least two progressions of disease during protracted trastuzumab-based therapy. Treatment consisted of gemcitabine (1000 mg/m(2) intravenous (iv) on days 1 and 8) and carboplatin (area under the curve 5 iv on day 1) applied every 3 weeks. RESULTS: Forty-two patients were registered. Disease control was 58%, with a median time-to-progression (TTP) of 7 months (range 1-12) and a median overall survival of 10.5 months (range 1-34). Patients were grouped as triple negative (ER and PR negative, HER-2 negative), HER-2 (HER-2 positive, ER and PR negative), luminal B (ER and/or PR positive and either HER-2 positive and/or high Ki67), and luminal A (ER and/or PR positive and HER-2 negative and low Ki67). For luminal A patients, disease control was lower (luminal A 34 vs. others 67%; P = 0.02), TTP was shorter (luminal A 2.4 months vs. others 6.3 months, P = 0.015), and overall survival was shorter (luminal A 7.5 months vs. others 11.7 months, P = 0.034) than for other subtypes. CONCLUSIONS: Gemcitabine and carboplatin are effective for pretreated patients with metastatic breast cancer. Luminal A subtype seems to fare poorly compared with other subtypes. Specific difference in gene expression might account for the different outcome.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Desoxicitidina/análogos & derivados , Idoso , Neoplasias da Mama/classificação , Desoxicitidina/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , Valor Preditivo dos Testes , Receptor ErbB-2/genética , Análise de Sobrevida , GencitabinaRESUMO
(1) Background: Several studies have investigated potential interactions between immune checkpoint inhibitors (ICIs) and commonly prescribed medications. Although acetaminophen (APAP) has not been considered susceptible to interaction with ICIs, recent research has shown that detectable plasma levels of this drug can hinder the efficacy of PD-1/PD-L1 blockade therapies. A reliable assessment of the potential interaction between APAP and ICIs in advanced non-small cell lung cancer (NSCLC) patients would be worthwhile since it is often prescribed in this condition. We sought to evaluate the impact of the concomitant use of APAP in patients with advanced NSCLC on PD-1/PD-L1 blockade using real-world evidence. (2) Methods: This study included consecutive patients with histologically proven stage IV NSCLC who underwent first-line therapy with pembrolizumab as a single agent or in combination with platinum-based chemotherapy, or second-line therapy with pembrolizumab, nivolumab, or atezolizumab. The intensity of APAP exposure was classified as low (therapeutic intake lasting less than 24 h or a cumulative intake lower than 60 doses of 1000 mg) or high (therapeutic intake lasting more than 24 h or a total intake exceeding 60 doses of 1000 mg). The favorable outcome of anti-PD-1/PD-L1 therapies was defined by durable clinical benefit (DCB). Progression-free survival (PFS) and overall survival (OS) were relevant to our efficacy analysis. Propensity score matching (PSM) methods were applied to adjust for differences between the APAP exposure subgroups. (3) Results: Over the course of April 2018 to October 2022, 80 patients were treated with first-line pembrolizumab either as single-agent therapy or in combination with platinum-based chemotherapy. During the period from June 2015 to November 2022, 145 patients were given anti-PD-1/PD-L1 blockade therapy as second-line treatment. Subsequent efficacy analyses relied on adjusted PSM populations in both treatment settings. Multivariate testing revealed that only the level of APAP and corticosteroid intake had an independent effect on DCB in both treatment lines. Multivariate Cox regression analysis confirmed high exposure to APAP and immunosuppressive corticosteroid therapy as independent predictors of shorter PFS and OS in both treatment settings. (4) Conclusions: Our findings would strengthen the available evidence that concomitant intake of APAP blunts the efficacy of ICIs in patients with advanced NSCLC. The detrimental effects appear to depend on the cumulative dose and duration of exposure to APAP. The inherent shortcomings of the current research warrant confirmation in larger independent series.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Acetaminofen , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Pontuação de Propensão , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Small cell lung cancer (SCLC) represents one of the most complex challenges in the oncological field, with a very slow advancement in research, contrary to the rapid evolutionary of the disease. For nearly two years, the mainstay of treatment for extensive-stage disease (ES-SCLC) has been the combination of platinum-based chemotherapy and immunotherapy, following the approval of atezolizumab and subsequently durvalumab, based on a modest, but significant improvement in overall survival compared to chemotherapy alone. The poor prognosis after the failure of first-line treatment explains the need to maximize the duration and efficacy of up-front systemic therapies, in particular, the emerging role of radiotherapy, also in ES-SCLC. On 10 November 2022, a meeting concerning the integrated treatment of patients with ES-SCLC was held in Rome and was attended by 12 specialists in oncology and radiotherapy from various centers in Lazio, under the direction of Federico Cappuzzo, Emilio Bria and Sara Ramella. The aim of the meeting was to share their clinical experience and to provide a series of practical indications in order to support physicians in the correct integration between first-line chemo-immunotherapy and radiotherapy treatments in ES-SCLC.
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Oncologia , Médicos , Humanos , Pacientes , ImunoterapiaRESUMO
Purpose: Metastatic breast cancer patients are the most prevalent oncology population with advanced disease facing COVID-19 pandemic. Immune responses after mRNA-based vaccination during treatment with CDK4/6 inhibitors or HER2-directed agents remain unclear. We conducted a prospective analysis to elucidate changes in antibody titers and lymphocyte counts following full course of mRNA-BNT162b2 (tozinameran) vaccination in recipients undergoing these targeted therapies. Methods: Patients who had received a booster dosing and had been treated for at least 6 months were eligible. Antibody titers against SARS-CoV-2 spike protein were measured at four subsequent time points. Immunophenotyping of circulating lymphocytes was performed before the third dose of tozinameran and four weeks later to quantify the absolute counts of CD3+CD4+ T-helper cells, CD3+CD8+ T-cytotoxic cells, CD19+ B cells, and CD56+CD16+ NK cells. We also assessed the incidence of breakthrough infections and investigated whether immune changes affect time-to-treatment failure (TTF) after booster vaccination. Results: The current analysis included 69 patients, of whom 38 (55%) and 31 (45%) were being treated with CDK4/6 inhibitors and HER2-targeted therapies, respectively. All participants received a third dose of tozinameran between September 23 and October 7, 2021. Multivariate analysis revealed that CDK4/6 inhibition predicted a significantly impaired humoral response after the booster dose. This detrimental effect was also evident for T-helper cell counts before the third immunization, but it disappeared in the subsequent evaluation. After a median follow-up of 22.3 months, we observed 19 (26%) cases of COVID-19 outbreaks, all experiencing favorable clinical outcomes. Univariate analysis showed a significant association between the onset of SARS-CoV-2 infections and the use of CDK4/6 inhibitors, as well as with an impaired antibody and T-helper cell response. Only the last two covariates remained independent predictors after multivariate testing. Dynamic variations in antibody titers and T-helper cell counts did not affect TTF in multivariate regression analysis. Conclusions: Our results confirm that the immune response to tozinameran is impaired by CDK4/6 inhibitors, increasing the odds of breakthrough infections despite the third vaccine dose. Current evidence recommends maintaining efforts to provide booster immunizations to the most vulnerable cancer patients, including those with advanced breast cancer undergoing CDK4/6 inhibition.
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BACKGROUND: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade are not fully understood. We conducted a prospective analysis of the Vax-On-Third-Profile study to evaluate the impact of circulating lymphocyte dynamics on disease outcomes in this subgroup of patients. METHODS: Recipients of booster dosing who had received before vaccination at least one course of an anti-PD-1/PD-L1 treatment for an advanced solid tumor were eligible. Immunophenotyping of peripheral blood was performed before the third dose of tozinameran (timepoint-1) and four weeks later (timepoint-2) to quantify the absolute counts of lymphocyte subpopulations, including CD3+CD4+ T cells, CD3+CD8+ T cells, B cells, and NK cells. Logistic regression was used to analyze the relationship between lymphocyte subsets and durable clinical benefit (DCB). The log-rank test and Cox regression model were applied to evaluate the relationship between lymphocyte subpopulations and both vaccine-related time-to-treatment failure (V-TTF) and overall survival (OS). RESULTS: We included a total of 56 patients with metastatic disease who were given a third dose of tozinameran between 23 September and 7 October 2021 (median age: 66 years; male: 71%). Most recipients had a diagnosis of lung cancer and were being treated with pembrolizumab or nivolumab. Compared to baseline, the third immunization resulted in an incremental change in the median counts of all lymphocyte subpopulations, which was statistically significant only for NK cells (p < 0.001). A significant correlation was found between NK cell counts and DCB at timepoint-2 (p < 0.001). Multivariate logistic regression analysis of DCB confirmed the predictive significance of high-level NK cell counts (p = 0.020). In multivariate Cox regression analysis, high-level NK cell counts independently predicted longer V-TTF [HR 0.34 (95% CI 0.14-0.80), p = 0.014] and OS [HR 0.36 (95% CI 0.15-0.89), p = 0.027]. CONCLUSIONS: Our data suggest expansion of NK cell counts as the most noteworthy change in circulating lymphocytes after the third dose of tozinameran in cancer patients receiving PD-1/PD-L1-targeted agents. This change correlated with enhanced therapeutic efficacy, improving the rate of disease control, and prolonging survival outcomes. Similar findings have not been previously reported, implying that they have proof-of-concept value and warrant further confirmation.
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(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5-17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210-505) vs. 2798 BAU/mL (95% CI 2323-3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3-3.6) vs. 16.2 months (95% CI 14.3-17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0-4.5) vs. 14.6 months (95% CI 11.9-16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes.
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COVID-19 , Neoplasias , Humanos , Vacinas contra COVID-19/uso terapêutico , Formação de Anticorpos , SARS-CoV-2 , Vacina BNT162 , Infecções Irruptivas , Neoplasias/tratamento farmacológicoRESUMO
Purpose: Clinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients. Methods: We conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities. Results: From March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts. Conclusion: Our findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes.
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BACKGROUND: The adaptive immune response following COVID-19 vaccination is essential for humoral immunogenicity and clinical protection against symptomatic infections. We present the results of circulating lymphocyte profiling and their correlation with antibody response in cancer patients tested serologically six months after receiving a two-dose schedule of mRNA-BNT162b2 vaccine. METHODS: Absolute counts of lymphocyte subsets were determined using peripheral blood immunophenotyping. We collected samples for flow cytometry analysis alongside quantitative detection of IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S1). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. RESULTS: 311 patients were evaluable for lymphocyte profiling and serologic testing. A preliminary multivariate analysis revealed that cytotoxic chemotherapy was the most consistent factor associated with lower counts of all lymphocyte subpopulations. T helper and B cells were found to be useful in predicting the occurrence of a positive seroconversion response using ROC curve analysis. A significant positive linear correlation was shown when anti-RBD-S1 IgG titers were compared to these lymphocyte subset counts. Univariate analysis indicated that antibody titers and seroconversion rates were significantly improved in the high-level T and B cell subgroups. Multivariate analysis confirmed these significant interactions, as well as the negative predictive value of immunosuppressive corticosteroid therapy. CONCLUSIONS: These findings suggest that simple and widely available peripheral counts of T helper and B cells correlate with humoral response to mRNA-BNT162b2 vaccine in actively treated cancer patients. Upon validation, our results could provide additional insights into the predictive assessment of vaccination efficacy.
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Formação de Anticorpos , Vacina BNT162 , COVID-19 , Neoplasias , Anticorpos Antivirais , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Humanos , Imunoglobulina G , Subpopulações de Linfócitos , Linfócitos , SARS-CoV-2 , Glicoproteína da Espícula de CoronavírusRESUMO
Background: There is no clear information on the proportion of patients who need therapy for immune-related thyroid dysfunction (irTD) or who need to delay, omit, or discontinue immunotherapy. Furthermore, it is not well known whether irTD correlates with better outcomes or not. Patients and Methods: We conducted a retrospective study in patients with metastatic non-small cell lung cancer (NSCLC) treated with anti-PD1 or anti-PD-L1. Results: Our study enrolled 75 patients, 25.3% of them developed immune-related thyroid dysfunction. Three patients delayed a course of immunotherapy due to irTD, 2 patients omitted a course and 1 patient permanently discontinued. In patients with irTD compared with those without irTD the ORR was 42.1% vs. 7.1% (p<0.001), DCR was 78.9% vs. 32.1% (p<0.001); mPFS was 15.7 vs. 3.6 months (p<0.001) and mOS was 18.6 months vs. 5.1 months (p<0.001). Conclusion: Immune-related thyroid dysfunction has a mild impact on the immunotherapy treatment program. The occurrence of irTD correlates with more favorable response and survival.
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The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. An IgG titer ≥ 4446 AU/mL was assumed as a correlate of 50% vaccine efficacy against symptomatic infections. A total of 258 patients on active treatment within the previous six months were enrolled between September 23 and October 7, 2021. The third dose resulted in an exponential increase in median anti-RBD-S1 IgG titer (P < 0.001), seroconversion rates (P < 0.001), and 50% vaccine efficacy rates (P < 0.001). According to ROC curve analysis, T helper and B cells were significantly associated with seroconversion responses at timepoint-1, whereas only B cells were relevant to 50% vaccine efficacy rates at timepoint-2. A positive linear correlation was shown between anti-RBD-S1 IgG titers and these lymphocyte subset counts. Multivariate analysis ruled out a potential role of T helper cells but confirmed a significant interaction between higher B cell levels and improved antibody response. These findings suggest that peripheral counts of B cells correlate with humoral response to the third dose of mRNA-BNT162b2 vaccine in actively treated cancer patients and could provide insights into a more comprehensive assessment of vaccination efficacy.
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Formação de Anticorpos , Vacina BNT162 , COVID-19 , Neoplasias , Humanos , Anticorpos Antivirais/sangue , Vacina BNT162/imunologia , COVID-19/prevenção & controle , Imunoglobulina G/sangue , Linfócitos , Neoplasias/imunologia , SARS-CoV-2RESUMO
Background Numerous research studies have looked into how the primary tumor location (PTL) affects patients' prognosis for colorectal cancer (CRC). Our research aimed to investigate the prognostic effects of PTL in patients with synchronous (SM) and metachronous (MM) colorectal cancer liver metastases (CRCLM). Material and methods From 2016 to 2021, we looked back at the records of patients at our institute who were affected by CRCLM. Results 109 patients were included, of whom 21.1% received CRCLM resection (R0=73.9%), with 57.7% having left-sided colon cancer (LCC) and 42.2% having right-sided colon cancer (RCC). SM predominated (69.7%). The median duration of follow-up was 21,3 months (95%CI=15,4-25,2). ≥5 hepatic metastases prevailed in the SM group (N=61; 83.5%). 21% of all patients underwent CRCLM resection (R0=78.2%). We observed a double rate of patients unresponsive to standard systemic antineoplastic treatments in the SM group (35.8% vs. 17.9% of the MM group) (p=0.27). We found a significantly longer median overall survival (OS) in patients with MM-LCC compared with the other groups (27.7 months; HR=0.3797; 95%CI=0.19-0.74; p=0.0205). The median OS, regardless of PTL, was higher in the MM group (16,5 months vs. 16,1 months; HR=0,29; 95%CI=0,13-0,67; p=0.0038) as well as progression-free survival (PFS) (11 months vs. 10,2 months; HR=0,61; 95%CI=0,33-1,12; p=0.11). Finally, in patients undergoing liver surgery, a noteworthy median OS was shown to be significantly in favor of patients with metachronous liver metastases from the primary left tumor (37.0 months; HR=0.47; 95%CI=0.11-1.96; p=0.0041). Conclusions Our real-life study demonstrated that patients with LCC, particularly MM-LCC, have the highest survival and that the timing of CRCLM should be a prognostic factor.
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Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no significant therapeutic advances over platinum and etoposide chemotherapy in the last 20 years until the introduction of immunotherapy. In 2020 atezolizumab, an immune checkpoint inhibitor against PD-L1 was approved in Italy in combination with carboplatin and etoposide for the first-line treatment of patients with extensive stage disease (ES-SCLC), becoming the new standard treatment. On May 20, 2021, a virtual meeting, directed by profs. Federico Cappuzzo and Emilio Bria, was held in which 14 clinicians from different oncology centers in Lazio, Umbria and Sardinia discussed the issues of ES-SCLC patients treatment, after the advent of immunotherapy. The aim of the meeting was to share their clinical experience and to provide a series of practical indications that can support clinicians in the management of ES-SCLC patients in first-line with chemo-immunotherapy.
Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo , Humanos , Itália , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
INTRODUCTION: Pemetrexed maintenance significantly improved progression-free survival (PFS) and overall survival (OS) in advanced nonsquamous non-small-cell lung cancer (NSCLC) patients not progressing after induction chemotherapy. OBJECTIVES: This study is aimed at examine the association of various clinical factor and survival in a real-world cohort analysis. MATERIALS AND METHODS: One hundred ninety-four patients were included and classified as "PM" cohort ("Pemetrexed Maintenance", including patients given with pemetrexed maintenance after induction chemotherapy, n=112), and "noPM" cohort ("no Pemetrexed Maintenance" including those discontinuing pemetrexed, n=82). RESULTS: The median PFS was 8.8 and 5.4 months in the PM and noPM cohorts, respectively (p=0.001). The median OS was 19.6 months in the "PM" cohort and 13.2 months in the "noPM" cohort (p<0.02). In the multivariate analysis, ECOG Performance Status (PS) 0 and maintenance therapy were independently associated with improved PFS and OS. A longer median PFS was reported in patients given ≥5 cycles of pemetrexed maintenance (p<0.01). DISCUSSION: These results further confirm the survival benefit of pemetrexed maintenance in a real-word population. All eligible advanced NSCLC patients should be strongly considered for at least 5 of pemetrexed maintenance.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Coortes , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pemetrexede/uso terapêutico , Resultado do TratamentoRESUMO
Lung cancer is a disease extremely heterogeneous in the molecular aspect and knowing the mutational profile of patients is essential in order to initiate the most appropriate treatment. In 2018, alectinib was approved in Italy for the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC), becoming a new therapeutic option for this patient group which constitutes approximately 3-7% of patients with NSCLC. On October 26th a virtual meeting was held in which 10 clinicians from various oncology centers in Lazio took part on the management of therapy of patients with Alk translocation, directed by Dr. Maria Rita Migliorino. The aim of the meeting was to share their clinical experience and to provide a series of practical that can help clinicians during treatment with target therapies in ALK-positive NSCLC.