Real-World Activity and Safety of Trifluridine-Tipiracil Plus Bevacizumab Therapy in Patients with Refractory Metastatic Colorectal Cancer

Background The combination of trifluridine-tipiracil and bevacizumab was compared with trifluridine-tipiracil monotherapy in a randomized, open-label, phase II trial, resulting in a statistically significant and clinically relevant improvement in progression-free survival (PFS), with tolerable toxicity in patients with refractory metastatic colorectal cancer (mCRC); however, evidence supporting the role of this combination in a real-world setting is limited. Objective The aim of our work was to provide further evidence on the activity and safety of this combination in a real-world series of Western mCRC patients refractory or intolerant to previous therapies. Patient and Methods We conducted a retrospective, observational study of patients with mCRC refractory or intolerant to standard therapies. Patients were treated with trifluridine-tipiracil and bevacizumab. Previous therapy with fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab, aflibercept, regorafenib, and cetuximab or panitumumab (only RAS wild-type) was allowed, as was previous participation in clinical trials. Clinicopathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety data were retrospectively collected and analyzed. Results We recorded 31 patients treated between 1 December 2017 and 30 June 2022. Median age was 69 years (range 38-82 years), 39% were male, 100% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, tumor location was left-sided in 77% of cases, 54% had synchronous presentation, 35% were RAS mutant, 3% were BRAF mutant, and 71% underwent primary tumor resection; 64% of patients had liver metastases, 55% had lung metastases, and 23% had peritoneal carcinomatosis. The median number of previous treatment lines was 2 (range 0-5), and 84% of patients received at least one previous anti-angiogenic agent. The ORR and DCR were 3% and 71%, respectively. With a median follow-up of 8 months (range 2-39), median PFS was 6 months (95% confidence interval [CI] 3.1-8.9 months) and median OS was 14 months (95% CI 10.1-17.8 months). Adverse events of any grade were reported in 58% of patients. The most common grade 3-4 toxicities were neutropenia (19%) and anemia (6%); 35% of patients required either dose delays or dose reductions due to toxicity. Granulocyte colony-stimulating factor (G-CSF) prophylaxis was administered either on first or subsequent cycles of treatment in 35% of patients. No treatment-related deaths occurred. Sixty percent of the patients who discontinued treatment eventually received one or more lines of subsequent therapy. Conclusions Our series provides further evidence on the activity and safety of the combination of trifluridine-tipiracil and bevacizumab in a real-world series of Western refractory mCRC patients

Eribulin for metastatic breast cancer (MBC) treatment: a retrospective, multicenter study based in Campania, south Italy (Eri-001 trial)

Background On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease.Methods In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC.Results Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3-4 toxicities were neutropaenia and neurotoxicity.Conclusions With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC

Eribulin for metastatic breast cancer (MBC) treatment. A retrospective, multicenter study based in Campania, South Italy (ERI-001 trial)

Background On the basis of the results of two pivotal phase III clinical trials, eribulin mesylate is currently approved in EU for the treatment of advanced breast cancer (aBC) in patients who have previously received an anthracycline and a taxane in either the adjuvant or the metastatic setting, and at least one chemotherapeutic regimen for metastatic disease.Methods In our study, we investigated the efficacy and tolerability of eribulin as second or further line chemotherapy in 137 women affected by aBC.Results Eribulin as monotherapy provided benefit in terms of progression-free survival (PFS), response rate (RR) and disease control rate (DCR) independently of its use as second or late-line therapy. The overall RR and DCR were 17.5% and 64%, respectively. In particular, DCR and overall RR were 50% and 13.6%, 65.4% and 21.1%, 70.4% and 14.8% and 66.7% and 16.7% in second, third, fourth and further lines of treatment, respectively. Median PFS (mPFS) according to the line of therapy was 5.7, 6.3, 4.5 and 4.0 months in patients treated with eribulin in second, third, fourth and over the fourth line, respectively. No significant difference in terms of mPFS was found between the various BC subtypes. Overall, eribulin resulted safe and most adverse events were of grade 1 or 2 and easily manageable. Grades 3-4 toxicities were neutropaenia and neurotoxicity.Conclusions With the limitations due to the observational nature of our findings, eribulin was shown to be an effective and safe therapeutic option in heavily pretreated patients with aBC

Microsatellite Status Detection in Gastrointestinal Cancers: PCR/NGS Is Mandatory in Negative/Patchy MMR Immunohistochemistry

SIMPLE SUMMARY: Microsatellite instability (MSI) detection has a high impact on eligibility for immune checkpoint inhibitors in gastrointestinal cancers. The appropriate detection of MSI represents the major critical issue in clinical practice, thus a better understanding of the limits related to MSI testing is needed to avoid misinterpretations. This study addresses the discordance between IHC and PCR/NGS testing in a large retrospective series of colorectal and gastric cancers in order to improve diagnosis. Our findings show a disagreement between negative/patchy expression IHC and PCR/NGS results, suggesting that molecular testing is mandatory in this subset of tumors. ABSTRACT: Background: Microsatellite instability (MSI) is a predictive biomarker for immune checkpoint inhibitors. The main goal was to investigate the discordance between IHC and PCR/NGS for MSI testing in gastrointestinal cancers. Methods: Two series were analyzed through IHC for mismatch-repair-system proteins (MMRP) and PCR, with one series of 444 colorectal cancers (CRC) and the other of 176 gastric cancers (GC). All cases with discordant results between IHC and PCR were analyzed by NGS. IHC staining was evaluated as follows: proficient MMR (pMMR), with all MMR positive; deficient MMR (dMMR), with the loss of one heterodimer; and cases with the loss/patchy expression of one MMR (lo-paMMR). Cases with instability in at least two markers by PCR were MSI-high (MSI-H) and with instability in one marker, MSI-low (MSI-L). Cases without instability were evaluated as microsatellite-stable (MSS). Results: In the CRC cohort, 15 out of 444 cases were dMMR and 46 lo-paMMR. Among the 15 dMMR, 13 were MSI-H and 2 MSS. Among the 46 lo-paMMR, 13 were MSI-H and 33 were MSS. In the GC cohort, 13 out of 176 cases were dMMR and 6 cases lo-paMMR. Among the 13 dMMR, 12 were MSI-H and only 1 was MSS. All six lo-paMMR cases were MSS. All NGS results were in agreement with PCR. Conclusions: In clinical practice, MMR–IHC could be used as a screening test and additional molecular analysis is mandatory exclusively in cases carrying loss/patchy MMR-IHC

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study

Abstract BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study

Cronache meridionali. A. III, n.1-12 (1956)

N. 1-2 (gennaio-febbraio 1964): Appello del Comitato nazionale per la rinascita del Mezzogiorno, 1 ; Sereni, E., La lotta per la conquista aella terra nel Mezzogiorno, P. 4 ; Viviani, L., Le condizioni di lauoro delle maestre, P. 23 ; Valenza, P., Venosa e la disoccupazione in Lucania, P. 33 ; Silipo, L., La legge speciale per la Calabria, P. 38 ; Cardia, U., La crisi del bacino carbonifero del Sulcis, P. 43 ; La distensione internazionale e lo sviluppo economico del Mezzogiorno, P. 53 ; Il II Congresso dell'Associazione dei contadini del Mezzogiorno, P. 67 ; Pirastu, I., Un convegno regionale dei pastori sardi, P. 68 ; Felicetti, N., I Comuni abruzzesi e molisani per il petrolio, P. 72 ; Pinna, G. L'attuazione dello Statuto regionale in Sardegna, P. 76 ; La commissione parlamentare d'inchiesta nelle fabbriche, P. 88 ; Sansone, N., Danilo Dolci: Banditi a Partinico, P. 95 ; Ricci, P., Alberto Consiglio: Antologia di poeti napoletani, P. 97 ; Mastroianni, G., Fausto Nicolini: Saggi vichiani, P. 101 ; Chiaromonte, G., Ferdinando Ventriglia : Panorami industriali, P. 104 ; Villari, R.,Giuseppe Coniglio: Il viceregno di Napoli nel secolo XVII, P. 106 ; Scibilia, A., Virgilio Titone: La Sicilia dalla dominazione spagnola all'unità d'Italia, P. 107 ; Natale, F., Gianvito Resta: Pascoli a Messina, P. 108 ;Giuseppe Garibaldi: La liberazione di Napoli, P. 110.N. 3 (marzo 1956): Basta con gli eccidi!, P. 113 ; Are, G., La crisi agricola in Sardegna, P. 115 ; Ovazza, M., L'attuazione della riforma agraria in Sicilia, P. 138 ; Alinovi, A., Savoia, C., Mariani, N., Scappini, R., Bianco, M., Mancini, G., e I. Pirastu (a cura di), Le conseguenze del maltempo, P. 145 ; Il Convegno degli ingegneri per la industrializzazione, P. 173 ; Cimino, M., Il cedimento di Alessi, P. 175 ; Chiaromonte, G., Gli «effetti economici» della Cassa, P. 179 ; Valenzi, M., Agostino Degli Espinosa: Il regno del Sud, P. 187 ; Villari, M., Pasquale Villani: Giuseppe Zurlo e la crisi dell'àntico regime nel regno di Napoli, P. 190 ; Sansone, N., Tommaso Fiore: Il cafone all'inferno, P. 191.N. 4 (aprile 1956): Le elezioni amministrative, P. 193 ; Il processo Dolci, P. 197 ; I soprusi prefettizi contro le amministrazioni Democratiche, P. 229 ; Matera, A., Il diritto all'assistenza, P. 234 ; Misefari, E., I comuni meridionali e la S. M. E., P. 237 ; Cassese, A., Eboli, P. 243 ; Cardaci, G., Mazzarino, P.248 ; Mafai, M., Pescara, 255 ; Ziccardi, A., Irsina, P. 259 ; Messinetti, S., Crotone, P. 261 ; Un dibattito sull'edilizia scolastica, P. 266 ; Villari, R.,Editore Passerin D'Entrèves: L'ultima battaglia politica di Cavour, P. 277 ; Formiggini, G., Leonardo Sciascia: Le parrocchie di Regalpetra, P. 280 ; Villari, P., Disordine amministrativo nelle province meridionali; Le ragioni di' un malcontento, Gli errori del governo, 283.N. 5 (maggio 1956): Le elezioni amministrative nel Mezzogiorno continentale, P. 289 ;Occhionero, L., Recenti libri sul petrolio italiano, P. 310 ; Spezzano, F., e R. Agostino, Sulla proroga della legge Sila, P. 324 ; Romano, A., Giampiero Carocci: Agostino Depretis e la politica interna italianadal 1876 al 1887, P. 337 ; Scibilia, A., Movimento operaio, P. 354 ; Villari, R., Giacobini italiani a cura di Delio Cantimori, P. 356 ; Dalla stampa 358.N. 6 (giugno 1956): Sereni, E., Capitale finanziario nelle campagne italiane, P. 361 ; Fortunato, G., Note sulle reazioni di Pontelandolio e Casalduni, P. 381 ; Alinovi, A., Il uoto di Napoli, P. 395 ;Avolio, G., Sui risultati elettorali nelle zone di riforma, P. 404 ; Sotgiu, G., Corrado Alvaro, P. 414 ; Locoratolo, L., Il P.S.I. nel Mezzogiorno, P. 418 ; Chiaromonte, G., Un dibattito sull'industrializzazione, P. 425 ; Amore, S., Alcuni esempi di «relazioni umane» nelle fabbriche napoletane, P. 432 ; Villari, R., G. Carano Donvito: Economisti di Puglia, P. 438.N. 7-8 (luglio-agosto 1956): Una minaccia contro la pace, P. 441 ; Il «secondo ciclo» della politica meridionale, P. 443 ; Incoronato, L., I minatori di Manoppello, P. 448 ; Napolitano, G., Prospettive dell'industrializzazione e linee di un intervento dell' I.r.i., P. 455 ; Cimino, M., La crisi del governo Alessi, P. 469 ; Lapiccirella, R., Un dibattito al Consiglio comunale di Napoli, P. 476 ; La formazione delle giunte comunali e provinciali, P. 483 ; Maglietta, C., Le ispezioni del lavoro, P. 494 ; Vitale, G., Problemi attuali degli enti di riforma, P. 496 ; Chiaromonte, G., Le variazioni nella distribuzione della proprietà fondiaria, P. 501 ; Di Lillo, G, “L. Piccardi R. Morghen. G. Calogero, L Borghi, H. Zanotti-Bianco, Dibattito sulla scuola”, P. 505 ; Villari, R., La «Statistica » del Regno di Napoli del 1811. Relazioni sulla provincia di Salerno. A cura di L. Cassese, P. 509 ; Ricci, P., Antologia, della canzone napoletana, P. 510 ; Franchetti, L., Capitali e agricoltura nel Mezzogiorno, P. 514 ; Franchetti, L., Contadini e proprietari, P. 517.N. 9 (settembre 1956): Unificazione socialista e rinascita del Mezzogiorno, P. 521 ; Renda, F., Il piano quinquennale per lo sviluppo economico e sociale della Sicilia, P. 524 ; Villari, R., Questione agraria e sviluppo, del capitalismo nel Risorgimento, P. 536 ; Vella, N., L'approvvigionamento idrico dell'Irpinia e del Sannio, P. 543 ; Nunziante, G., La situazione edilizia napoletana, P. 553 ; Granati, F., La difesa del prezzo del pomodoro nel Salernitano, P. 556 ; Napolitano, G., Natura e limiti del programma di Vanoni, P. 570 ; Chiaromonte, G., Le finanze comunali net Mezzogiorno, P. 576 ; Villari, R., Sull'evoluzione d'ella proprietà fondiaria privata in Italia, P. 579 ; Chiaromonte, G., Campilli, Malvestiti, Moro, Pella, Piccioni, Porzio, Scelba, Segni, Spataro, Togni, Tridente: Il dialogo continua alIa Fiera del Levante e la politica meridionalistica, P. 584 ; Sonnino, S., L'alienazione dei bent demaniali ed ecclesiastici in Sicilia, P. 587.N. 10 (ottobrebre 1956): Chiaromonte, G., Per la pace e per la libertà, P. 593; Montalbano, G., Corte costituzionale e Alta Corte siciliana, P. 596 ; Raucci, E., L'Ente Regione strumento di democrazia e di progresso, P. 612 ; Corbi, B., Problemi di economia e politica agraria nel Fucino, P. 646 ; Gigliotti, A., L'opera Sila ela riforma fondiaria in Calabria, P. 650 ; Chiaromonte, G., Il convegno di Sorrento e il carattere « settoriale » della questione meridionale, P. 661 ; Il Mezzogiorno al Congresso di Trento, P. 665 ; Santarelli, G., Giampiero Carocci, Giovanni Amendola nella crisi della Stato italiano, P. 669 ; Villari, R., René Bouvier e Andrè Laffargue, La vie napolitaine au XVIIIe siècle, P. 671.N. 11 (novembre 1956): Ingrao, P., Per una politica di amicizia col mondo arabo, P. 673 ; Vitale, G.,Il movimento democratico e la riforma agraria, P. 679 ; Cimino, M., Personaggi ed eventi della crisi politica siciliana, P. 690 ; Felicetti, N., L'emigrazione dall'Abruzzo, P. 695 ; Gallo, N., l patti colonici nei bergamotteti del Reggino, P. 706 ; Rossi, C., Le finanze delle province meridionali, P. 723 ; La Cassa per il Mezzogiorno a metà strada, P. 727 ; Renda, F., Ed Reid, La mafia, P. 732 ; Villari, R., Giuliano Procacci, Le elezioni del 1874 e l'opposizione meridionale, P. 735 ; Ricci, P., Vincenzo Dattilo, Castel dell'Ovo, P. 737 ; L'Inchiesta agraria (dalla Rassegna settimanale). 740.N. 12 (dicembre 1956): Napolitano, G., La crisi della politica meridionale e la legge di proroga della Cassa, P. 745 ; Chiaromonte, G., Le regioni arretrate ID Jugoslavia, P. 754 ; Conte L., Effetti della meccanizzazione nell'agricoltura del Foggiano, P. 766 ; Faletra, G., La cassa per il Mezzogiorno in Sicilia, P. 773 ; Levrero, S., La posizione dei lavoratori sullo sviluppo :industriale di Napoli, P. 793 ; Villari, L., Studi in onore di Antonio Genovesi nel bicentenario della istituzione della cattedra di economia, P. 799 ; La questione sociale in Italia (dalla Rassegna settimanale), P. 804