External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

Estudio de la supervivencia global y de los factores pronósticos del cáncer gástrico localizado tratado de forma radical en el Hospital Parc Taulí de Sabadell entre los años 2004 y 2020

Estudi observacional, unicèntric, retrospectiu dels pacients afectes de càncer gàstric no metastàtic, tractats amb intenció radical a l'Hospital Parc Taulí de Sabadell des del 01 de gener de 2004 fins al 31 de desembre de 2020. S'hi van incloure un total de 266 pacients, intervinguts de manera radical. L'objectiu principal va ser determinar la supervivència global i la supervivència lliure de malaltia. Els objectius secundaris, determinar la morbiditat i mortalitat quirúrgica, l'efecte de la cirurgia radical, tipus de limfadenectomia, localització del tumor, el valor pronòstic del sexe, l'edat al diagnòstic i les característiques patològiques del tumor (classificació de Lauren, grau histològic, invasió perineural i vasculolinfàtica) en la supervivència global i en la supervivència lliure de malaltia, a més de l'efecte dels tractaments complementaris realitzats (QT adjuvant, QTRT adjuvant i QT perioperatòria).Estudio observacional, unicéntrico, retrospectivo de los pacientes afectos de cáncer gástrico no metastásico, tratados con intención radical en el Hospital Parc Taulí de Sabadell desde el 01 de enero de 2004 hasta el 31 de diciembre de 2020. Se incluyeron un total de 266 pacientes, intervenidos de manera radical. El objetivo principal fue determinar la supervivencia global (SG) y la supervivencia libre de enfermedad (SLE). Los objetivos secundarios, determinar la morbilidad y la mortalidad quirúrgica, el efecto de la cirugía radical, tipo de linfadenectomía, localización del tumor, el valor pronóstico del sexo, la edad al diagnóstico y las características patológicas del tumor (clasificación de Lauren, grado histológico, invasión perineural y vasculolinfática) en la SG y en la SLE, además del efecto de los tratamientos complementarios realizados (QT adyuvante, QTRT adyuvante y QT perioperatoria).This is a retrospective, single-center, observational study of patients with non-metastatic gastric cancer who underwent radical treatment at the Parc Taulí Hospital in Sabadell from January 1st, 2004 to December 31st, 2020. A total of 266 patients who underwent radical surgery were included. The primary objective was to determine overall survival (OS) and disease-free survival (DFS). Secondary objectives included determining surgical morbidity and mortality, the effect of radical surgery, type of lymphadenectomy, tumor location, prognostic value of sex, age at diagnosis, and pathological characteristics of the tumor (Lauren classification, histological grade, perineural and vasculolymphatic invasion) on OS and DFS, as well as the effect of adjuvant treatments (adjuvant chemotherapy, adjuvant chemoradiotherapy, and perioperative chemotherapy)

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma : data from the AGAMENON-SEOM registry

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials

Second-line treatment in advanced gastric cancer: Data from the Spanish AGAMENON registry

Background: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. Materials and methods: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). Results: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). Conclusion: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines