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Papers by Gabriele Minuti
Recenti progressi in medicina, 2021
Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no si... more 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.
Thoracic Cancer
Improved outcome in tobacco smoking patients with non‐small cell lung cancer (NSCLC) following im... more Improved outcome in tobacco smoking patients with non‐small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first‐line immunotherapy in patients with high PD‐L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts.
European Journal of Cancer
European Journal of Cancer
Journal for ImmunoTherapy of Cancer
BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associa... more BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy ...
Journal of Clinical Oncology
e14574 Background: Brain metastases (BM) occur in 1-4% of metastatic colorectal cancer (mCRC) pat... more e14574 Background: Brain metastases (BM) occur in 1-4% of metastatic colorectal cancer (mCRC) patients (pts). Retrospective series evidence that pts with a long survival from the diagnosis of mCRC are more frequently affected. Moreover, BM seem to be associated with lung metastases and KRAS activating mutations. The identification of clinical and molecular features correlated with BM may allow to define a subgroup more likely to develop BM, thus to benefit from neuroimaging follow up and early treatment. Methods: We prospectively tested the hypothesis that a higher incidence of BM occurs in a population of mCRC pts with a survival time from the diagnosis of mCRC ≥10 months, lung metastases and KRAS exons 2 and 3 mutations. Given a reported incidence of BM in unselected mCRC of around 3% (H0) and expecting an incidence in an “at risk” population selected on the basis of the 3 above reported features of 10% (H1), setting α and β errors to 0.05 and 0.10 respectively, we adopted the Fle...
Journal for ImmunoTherapy of Cancer
Background: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer ... more Background: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. Methods: Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. Results: Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM-cases. BoM+ had lower overall response rate (ORR
Journal of Clinical Oncology
3067Background: Nivolumab is the first checkpoint inhibitor approved for the treatment of squamou... more 3067Background: Nivolumab is the first checkpoint inhibitor approved for the treatment of squamous non small cell lung cancer (Sq-NSCLC) to show a survival benefit in a randomised phase III trial. ...
Clinical Cancer Research
Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosi... more Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations. Patients and Methods: Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts. Results: From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2-30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14-mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts. Conclusions: Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.
Journal of Clinical Oncology
e11575 Background: Approximately 5-10% of breast cancer (BC) patients have metastases at the time... more e11575 Background: Approximately 5-10% of breast cancer (BC) patients have metastases at the time of diagnosis (de novo stage IV), suggesting distinct biological and clinical implications as compared to those relapsing after prior treatment for early stage BC (recurrent disease). We evaluated the patterns of care and clinical outcomes of HER2-positive MBC receiving first line trastuzumab-based therapy, according to the type of metastatic presentation. Methods: This is a retrospective cohort study conducted in 14 Italian centers within the GIM (Gruppo Italiano Mammella: Italian Breast Group). Consecutive patients undergoing first-line trastuzumab-based therapy were eligible for the study. Analyses were performed according to the type of presentation of metastatic disease (de novo or recurrent). Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models controlling for relevant demographic, clinicopathologic and therapy characterist...
Oncotarget
Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immuno... more Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1). Although PD-L1 expression seems predictive of response to anti-PD-1/PD-L1 agents, its prognostic value is unclear. In this study we investigated the prognostic value of PD-L1 expression and its correlation with clinical-pathological characteristics in a cohort of surgically resected NSCLC. Material and methods: PD-L1 expression was evaluated in 289 surgically resected NSCLC samples by immunohistochemistry. Our cohort included patients not exposed to adjuvant chemotherapy. PD-L1 status was defined as: 1) PD-L1 high (tumor proportion score, TPS≥50%), PD-L1 low (TPS 1-49%), PD-L1 negative (TPS<1%); 2) PD-L1 positive (TPS≥50%) and negative (TPS<50%); 3) as a continuous variable. Results: Patients were mostly males (79%), former or current smokers (81%), with a median age of 67 years, non-squamous histology (67.5%) and high-grade tumors (55%). PD-L1 tumors were 18.7%. There was no significant association with sex, age, smoking status and histology. A strong correlation between high PD-L1 expression and tumor grade was detected. The difference in median OS in the different groups of patients was not statistically significant. Conclusion: PD-L1 is not prognostic in surgically resected NSCLC. The association with tumor differentiation suggests that grading could represent an easy-to-assess tool for selecting subjects potentially sensitive to immunotherapy warranting further investigations.
Journal of Clinical Oncology
Journal of Thoracic Oncology
and MAP2K1 were detected each with less than 1%. Conclusion: In a representative Brazilian cohort... more and MAP2K1 were detected each with less than 1%. Conclusion: In a representative Brazilian cohort, the percentage of rare mutations detected matches data published elsewhere. An extended cohort and health economics data will be presented during the meeting and will allow a better description of the rare mutations and the potential impact they may have in the landscape of lung adenocarcinoma treatment in Brazil. These data may support drug access decisions in the country.
Recenti progressi in medicina, 2021
Small cell lung cancer (SCLC) is an aggressive disease, difficult to treat. There have been no si... more 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.
Thoracic Cancer
Improved outcome in tobacco smoking patients with non‐small cell lung cancer (NSCLC) following im... more Improved outcome in tobacco smoking patients with non‐small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first‐line immunotherapy in patients with high PD‐L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts.
European Journal of Cancer
European Journal of Cancer
Journal for ImmunoTherapy of Cancer
BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associa... more BackgroundSome concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate.MethodsWe present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression ≥50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses.Results950 and 595 patients were included in the pembrolizumab and chemotherapy ...
Journal of Clinical Oncology
e14574 Background: Brain metastases (BM) occur in 1-4% of metastatic colorectal cancer (mCRC) pat... more e14574 Background: Brain metastases (BM) occur in 1-4% of metastatic colorectal cancer (mCRC) patients (pts). Retrospective series evidence that pts with a long survival from the diagnosis of mCRC are more frequently affected. Moreover, BM seem to be associated with lung metastases and KRAS activating mutations. The identification of clinical and molecular features correlated with BM may allow to define a subgroup more likely to develop BM, thus to benefit from neuroimaging follow up and early treatment. Methods: We prospectively tested the hypothesis that a higher incidence of BM occurs in a population of mCRC pts with a survival time from the diagnosis of mCRC ≥10 months, lung metastases and KRAS exons 2 and 3 mutations. Given a reported incidence of BM in unselected mCRC of around 3% (H0) and expecting an incidence in an “at risk” population selected on the basis of the 3 above reported features of 10% (H1), setting α and β errors to 0.05 and 0.10 respectively, we adopted the Fle...
Journal for ImmunoTherapy of Cancer
Background: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer ... more Background: Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. Methods: Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. Results: Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM-cases. BoM+ had lower overall response rate (ORR
Journal of Clinical Oncology
3067Background: Nivolumab is the first checkpoint inhibitor approved for the treatment of squamou... more 3067Background: Nivolumab is the first checkpoint inhibitor approved for the treatment of squamous non small cell lung cancer (Sq-NSCLC) to show a survival benefit in a randomised phase III trial. ...
Clinical Cancer Research
Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosi... more Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations. Patients and Methods: Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts. Results: From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2-30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14-mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts. Conclusions: Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.
Journal of Clinical Oncology
e11575 Background: Approximately 5-10% of breast cancer (BC) patients have metastases at the time... more e11575 Background: Approximately 5-10% of breast cancer (BC) patients have metastases at the time of diagnosis (de novo stage IV), suggesting distinct biological and clinical implications as compared to those relapsing after prior treatment for early stage BC (recurrent disease). We evaluated the patterns of care and clinical outcomes of HER2-positive MBC receiving first line trastuzumab-based therapy, according to the type of metastatic presentation. Methods: This is a retrospective cohort study conducted in 14 Italian centers within the GIM (Gruppo Italiano Mammella: Italian Breast Group). Consecutive patients undergoing first-line trastuzumab-based therapy were eligible for the study. Analyses were performed according to the type of presentation of metastatic disease (de novo or recurrent). Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models controlling for relevant demographic, clinicopathologic and therapy characterist...
Oncotarget
Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immuno... more Introduction: For several years non-small cell lung cancer (NSCLC) has been considered non-immunogenic. Recent advances in antitumor immunity brought to the discovery of checkpoints that modulate immune response against cancer. One of them is programmed death receptor 1 (PD-1) and its ligand (PD-L1). Although PD-L1 expression seems predictive of response to anti-PD-1/PD-L1 agents, its prognostic value is unclear. In this study we investigated the prognostic value of PD-L1 expression and its correlation with clinical-pathological characteristics in a cohort of surgically resected NSCLC. Material and methods: PD-L1 expression was evaluated in 289 surgically resected NSCLC samples by immunohistochemistry. Our cohort included patients not exposed to adjuvant chemotherapy. PD-L1 status was defined as: 1) PD-L1 high (tumor proportion score, TPS≥50%), PD-L1 low (TPS 1-49%), PD-L1 negative (TPS<1%); 2) PD-L1 positive (TPS≥50%) and negative (TPS<50%); 3) as a continuous variable. Results: Patients were mostly males (79%), former or current smokers (81%), with a median age of 67 years, non-squamous histology (67.5%) and high-grade tumors (55%). PD-L1 tumors were 18.7%. There was no significant association with sex, age, smoking status and histology. A strong correlation between high PD-L1 expression and tumor grade was detected. The difference in median OS in the different groups of patients was not statistically significant. Conclusion: PD-L1 is not prognostic in surgically resected NSCLC. The association with tumor differentiation suggests that grading could represent an easy-to-assess tool for selecting subjects potentially sensitive to immunotherapy warranting further investigations.
Journal of Clinical Oncology
Journal of Thoracic Oncology
and MAP2K1 were detected each with less than 1%. Conclusion: In a representative Brazilian cohort... more and MAP2K1 were detected each with less than 1%. Conclusion: In a representative Brazilian cohort, the percentage of rare mutations detected matches data published elsewhere. An extended cohort and health economics data will be presented during the meeting and will allow a better description of the rare mutations and the potential impact they may have in the landscape of lung adenocarcinoma treatment in Brazil. These data may support drug access decisions in the country.