Background In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS. Methods Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m 2 twice daily on days 1-5 and 8-12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≥ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≥ 2. Results Of 507 randomized patients, 496 had baseline QoL data available. The analysis cutoff was 6 cycles for trifluridine/ tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS. Conclusion QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo. Trial registration ClinicalTrials.gov number: NCT02500043
4043 Background: The phase 3, randomized, double-blind, placebo-controlled study (TAGS) evaluated the efficacy and safety of FTD/TPI (35 mg/m² given orally twice a day on days 1–5 and 8–12 of a 28-day cycle) in mGC patients who had previously received≥2 prior regimens for advanced disease and demonstrated a clinically relevant and statistically significant benefit in OS and PFS with a predictable and manageable safety profile. HRQoL data and association between QoL and time to ECOG status deterioration (2 or more) are reported here. Methods: HRQoL was evaluated using EORTC QLQ-C30 and the gastric-specific module (QLQ-STO22) questionnaires at baseline and at every 4 weeks thereafter until treatment discontinuation. Prespecified key HRQoL were changes from baseline and time to deterioration. Changes ≥10 points were deemed clinically relevant. A time-dependent Cox-regression analysis was performed to evaluate the association of 10-point Global Health Status deterioration with worsening ECOG status. Results: Of 507 patients randomized, 332/337 (98.5%) of FTD/TPI and 164/170 (96.5%) of placebo had baseline QoL data. Overall compliance was 84% for both questionnaires. Demographic and disease were generally balanced between the two groups; QoL scores were also similar between groups. HRQoL was largely maintained during treatment in both arms for most items; mean changes from baseline remained under the 10-point threshold. Clinically relevant changes from baseline were observed only for pain relief at cycle 2 (favouring FTD/TPI); and improved role functioning at cycle 3 (favouring placebo). In a sensitivity analysis including death or progression as an event, FTD/TPI was associated with a positive trend suggesting a reduced risk of QoL deterioration across all scales compared to placebo (HRs ranged from 0.57 to 0.74. A 10-point Global Health Status deterioration was associated with a worsening ECOG status (HR, 95% CI, 1.5, 1.2 to 1.86). Conclusions: During the treatment period, HRQoL remained stable for most functional and symptom scales in both arms, suggesting that HRQoL is largely maintained with FTD/TPI. Treatment with FTD/TPI was associated with a positive trend toward a lower risk of QoL deterioration than placebo across all scales. Changes in QoL were informative for patients ‘expected ECOG status. Clinical trial information: NCT02500043.
4040 Background: Gastric cancer is the 5th cancer diagnosis and 3rd cause of cancer death worldwide. Metastatic gastric cancer (mGC) has a median survival of 11 months. mGC is an heterogeneous disease and different biologic characteristics may justify differential therapeutic opportunities. Tumors with homologous recombination (HR) deficiency may benefit with treatment with PARP inhibitors or immune checkpoint inhibitors. The purpose of this study was to evaluate the prevalence and prognostic impact of altered expression of HR proteins as surrogates for homologous recombination deficiency (HRD) in mGC. Methods: Multicenter retrospective cohort of mGC treated with platinum-based chemotherapy. HRD defined as absence of at least one of the following proteins: ATM, ATR, CHK2, RAD51, RAD52, BRCA1, BRCA2, MRE11 by immunohistochemistry. Survival time calculated as the difference between first cycle of platinum-based chemotherapy and death or last observation. Association between HRD and survival examined with log-rank test. Results: 440 patients included, of which 70% male, with mean age of 58 years (SD: 11). 75% of patients had mGC at diagnosis, 43% had 2 or more organs involved and 63% were registered as ECOG 0 or 1 at the start of first line chemotherapy. The most common histologic subtype was tubular adenocarcinoma (44%) followed by diffuse carcinoma (32%). HRD was noted in 196 (45%) cases (95%CI: 40%-49%). The most commonly altered proteins were ATM (21%) and BRCA2 (18%). In HRD tumors, 99 (51%) had altered expression of only one HR protein; 47 (24%) had altered expression of two HR proteins; the remaining cases had altered expression of 3 or more proteins. After a median follow up of 11 months, median survival for the cohort was 11 months (95% CI 9-12). HRD was associated with an improved survival, HR = 0.61 (95%CI: 0.48-0.78, p < 0.001), that remained significant after adjustment for sex, age, performance status and disease status (HR = 0.63; 95%CI: 0.48-0.82; p < 0.001). Conclusions: HRD phenotype was present in 45% of mGC cases and is associated with improved prognosis for mGC treated with platinum-based first line chemotherapy.
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