Impacte del tractament quimioteràpic en terceres línies i posteriors en el mesotelioma pleural maligne

La baixa incidència del mesotelioma maligne dificulta la realització d'estudis clínics que aportin coneixement de la millor seqüència de tractaments a administrar. No existeix consens més enllà de la primera línea de quimioteràpia basada en la combinació de cisplatí i pemetrexed. S'ha recollit una mostra de pacients diagnosticats a l'Hospital Germans Trias i Pujol entre els anys 2003 i 2010. S'han avaluat les característiques dels pacients així com la seva supervivència. S'ha realitzat un subanàlisi en el subgrups de malalts que han rebut tres o més línies de tractament quimioteràpic

Multicenter Real-World Data of Subsequent Chemotherapy after Progression to PARP Inhibitors in a Maintenance Relapse Setting

Càncer d'ovaris; Inhibidors PARP; QuimioteràpiaCáncer de ovarios; Inhibidores PARP; QuimioterapiaOvarian cancer; PARP inhibitors; ChemotherapyBackground: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8-17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6-9.2), and median OS (mOS) of 20.6 months (95% CI 13.6-28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2-22.2] and 10.3 [IQR 7.4-14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5-8.6) versus 7.5 months (95% CI 6.5-10.1, p = 0.03), and 16.4 (95% CI 9.3-27.5) versus 24.2 months (95% CI 17.2-NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients

Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

Metastatic prostate cancer; Chemotherapy; Hormonal therapyCáncer de próstata metastásico; Quimioterapia; Terapia hormonalCàncer de pròstata metastàtic; Quimioteràpia; Teràpia hormonalBackground: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

Impacte del tractament quimioteràpic en terceres línies i posteriors en el mesotelioma pleural maligne

La baixa incidència del mesotelioma maligne dificulta la realització d’estudis clínics que aportin coneixement de la millor seqüència de tractaments a administrar. No existeix consens més enllà de la primera línea de quimioteràpia basada en la combinació de cisplatí i pemetrexed. S’ha recollit una mostra de pacients diagnosticats a l’Hospital Germans Trias i Pujol entre els anys 2003 i 2010. S’han avaluat les característiques dels pacients així com la seva supervivència. S’ha realitzat un subanàlisi en el subgrups de malalts que han rebut tres o més línies de tractament quimioteràpic

Impacte del tractament quimioteràpic en terceres línies i posteriors en el mesotelioma pleural maligne

La baixa incidència del mesotelioma maligne dificulta la realització d'estudis clínics que aportin coneixement de la millor seqüència de tractaments a administrar. No existeix consens més enllà de la primera línea de quimioteràpia basada en la combinació de cisplatí i pemetrexed. S'ha recollit una mostra de pacients diagnosticats a l'Hospital Germans Trias i Pujol entre els anys 2003 i 2010. S'han avaluat les característiques dels pacients així com la seva supervivència. S'ha realitzat un subanàlisi en el subgrups de malalts que han rebut tres o més línies de tractament quimioteràpic