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Metastatic colorectal cancer; Renal impairment; Safety Cáncer colorrectal metastásico; Insuficiencia renal; Seguridad Càncer colorectal metastàtic; Insuficiència renal; Seguretat Background Trifluridine/tipiracil (FTD/TPI) showed clinical benefit, including improved survival and manageable safety in previously treated patients with metastatic colorectal (mCRC) or gastric/gastroesophageal junction (mGC/GEJC) cancer in the phase III RECOURSE and TAGS trials, respectively. A pooled analysis was conducted to further characterize FTD/TPI safety, including management of haematologic toxicities and use in patients with renal or hepatic impairment. Patients and methods Adults with ≥2 prior regimens for advanced mGC/GEJC or mCRC were randomized (2 : 1) to FTD/TPI [35 mg/m2 twice daily days 1-5 and 8-12 (28-day cycle); same dosage in both trials] or placebo plus best supportive care. Adverse events (AEs) were summarized in the safety population (patients who received ≥1 dose) and analysed by renal/hepatic function. Results TAGS and RECOURSE included 335 and 533 FTD/TPI-treated and 168 and 265 placebo-treated patients, respectively. Overall safety of FTD/TPI was similar in TAGS and RECOURSE. Haematologic (neutropenia, anaemia) and gastrointestinal (nausea, diarrhoea) AEs were most commonly observed. Laboratory-assessed grade 3-4 neutropenia occurred in 37% (TAGS)/38% (RECOURSE) of FTD/TPI-treated patients (median onset: 29 days/55 days), and 96% (TAGS)/97% (RECOURSE) of cases resolved regardless of renal/hepatic function. Supportive medications for neutropenia were received by 17% (TAGS) and 9% (RECOURSE); febrile neutropenia was reported in 2% and 4%, respectively. Overall grade ≥3 AEs were more frequent in patients with moderate renal impairment [81% (TAGS); 85% (RECOURSE)] versus normal renal function (74%; 67%); anaemia and neutropenia were more common in patients with renal impairment. FTD/TPI safety (including haematologic AEs) was consistent across patients with normal and mildly impaired hepatic function. Conclusions These results support FTD/TPI as a well-tolerated treatment in patients with mGC/GEJC or mCRC, with a consistent safety profile. Safety was largely similar in patients with normal or mildly impaired renal/hepatic function; however, patients with renal impairment should be monitored for haematologic toxicities. This work was supported by Taiho Oncology, Inc. and Taiho Pharmaceutical (no grant number). This analysis was funded by Taiho Oncology, Inc. Professional medical writing and editorial assistance were provided by Vasupradha Vethantham, Meredith Kalish, and Jennifer L. Robertson at Ashfield MedComms, an Inizio company, funded by Taiho Oncology, Inc.

A new way to study the spin-isospin dependence of the $ΞN$ interaction is explored through the energy levels of $ΞNα$ and $ΞNαα$ systems with $α$ being a spectator to attract the $ ΞN$ pair without changing its spin-isospin structure. By using the Gaussian expansion method (GEM) with the state-of-the-art $ΞN$ potential obtained from lattice QCD calculations, it is found that $ΞNαα$ has spin-doublet bound states with $J^π={1^-}$ and $2^-$ in both isospin triplet and singlet channels. The inversion of the $1^-$-$2^-$ spin-doublet between the iso-triplet and the iso-singlet is found to be strongly correlated with the relative strengths of the $ΞN$ interaction in the $^{11}{\rm S}_0, ^{13}{\rm S}_1,^{31}{\rm S}_0$ and $^{33}{\rm S}_1$ channels. The $(K^-, K^+)$ and $(K^-,K^0)$ reactions on the $^{10}$B target are proposed to produce those bound states., 5pages, 5figures

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We conducted the coincidence measurement of $��$ particles inelastically scattered from ${}^{20}$Ne at $0^{\circ}$ and decay charged particles in order to search for the alpha-particle condensed state. We compared the measured excitation-energy spectrum and decay branching ratio with the statistical-decay-model calculations, and found that the newly observed states at $E_x$ = 23.6, 21.8, and 21.2 MeV in ${}^{20}$Ne are strongly coupled to a candidate for the 4$��$ condensed state in ${}^{16}$O. This result presents the first strong evidence that these states are the candidates for the 5$��$ condensed state., 6 pages, 5 figures. The part of the analysis is updated, and some discussions are added

Experimental evidence exists that the $��$-nucleus interaction is attractive. We search for $NN��$ and $NNN��$ bound systems on the basis of the AV8 $NN$ potential combined with either a phenomenological Nijmegen $��N$ potential or a first principles HAL QCD $��N$ potential. The binding energies of the three-body and four-body systems (below the $d+��$ and $^3{\rm H}$/$^3{\rm He}+��$ thresholds, respectively) are calculated by a high precision variational approach, the Gaussian Expansion Method. Although the two $��N$ potentials have significantly different isospin ($T$) and spin ($S$) dependence, the $NNN��$ system with quantum numbers $(T=0, J^��=1^+$) appears to be bound (one deep for Nijmegen and one shallow for HAL QCD) below the $^3{\rm H}$/$^3{\rm He}+��$ threshold. Experimental implications for such a state are discussed., 5 pages, 5 figures, preprint

Bivalent H3K4me3 and H3K27me3 chromatin domains in embryonic stem cells keep active developmental regulatory genes expressed at very low levels and poised for activation. Here, we show an alternative and previously unknown bivalent modified histone signature in lineage-committed mesenchymal stem cells and preadipocytes that pairs H3K4me3 with H3K9me3 to maintain adipogenic master regulatory genes (Cebpa and Pparg) expressed at low levels yet poised for activation when differentiation is required. We show lineage-specific gene-body DNA methylation recruits H3K9 methyltransferase SETDB1, which methylates H3K9 immediately downstream of transcription start sites marked with H3K4me3 to establish the bivalent domain. At the Cebpa locus, this prevents transcription factor C/EBPβ binding, histone acetylation, and further H3K4me3 deposition and is associated with pausing of RNA polymerase II, which limits Cebpa gene expression and adipogenesis.

We perform ab initio self-consistent Green's function calculations of the closed shell nuclei $^{\rm 4}$He, $^{\rm 16}$O and $^{\rm 40}$Ca, based on two-nucleon potentials derived from Lattice QCD simulations, in the flavor SU(3) limit and at the pseudo-scalar meson mass of 469~MeV/c$^{\rm 2}$. The nucleon-nucleon interaction is obtained using the HAL QCD method and its short-distance repulsion is treated by means of ladder resummations outside the model space. Our results show that this approach diagonalises ultraviolet degrees of freedom correctly. Therefore, ground state energies can be obtained from infrared extrapolations even for the relatively hard potentials of HAL QCD. Comparing to previous Brueckner Hartree-Fock calculations, the total binding energies are sensibly improved by the full account of many-body correlations. The results suggest an interesting possible behaviour in which nuclei are unbound at very large pion masses and islands of stability appear at first around the traditional doubly-magic numbers when the pion mass is lowered toward its physical value. The calculated one-nucleon spectral distributions are qualitatively close to those of real nuclei even for the pseudo-scalar meson mass considered here., Comment: 7 pages, 4 figures, RIKEN-QHP-286, RIKEN-iTHEMS-Report-17

To construct a framework for monitoring the effectiveness of influenza vaccine, we retrospectively surveyed elderly (or = 65 years old) people living in rural areas of Kyoto prefecture, Japan, using a self-administered questionnaire, for their influenza-related symptoms during the peak influenza season of 2003-2004. A total of 2301 elderly individuals responded, of whom 1533 (66.6%) had been vaccinated. The odds ratio (OR) of vaccination for fever ofor = 38 degrees C, adjusted for sex, age and underlying conditions, was 0.77 (95% confidence interval (CI), 0.40-1.47), and the OR for a diagnosis of influenza in clinics was 0.81 (95% CI, 0.41-1.57). These findings suggested that the vaccine was 20% effective, although this effectiveness was not statistically significant.

Interstitial lung disease (ILD) can be separated into two groups: (i) that in which the causes are known; and (ii) that in which the etiologies have not been determined. Meanwhile, complement is essential for the inflammatory response and complement systems have been recognized as factors involved in organizing ILD. In the present study we investigated whether there were any differences in complement-related membrane proteins on lymphocytes and alveolar macrophages in bronchoalveolar lavage fluids (BALF) between different ILD. Bronchoalveolar lavage fluid samples were obtained from 12 patients and eight healthy individuals. Bronchoalveolar lavage fluid cells were incubated with monoclonal antibodies (mAbs) against C3b/C4b receptor (CR1), C3bi receptor (CR3), membrane cofactor protein (MCP) and decay accelerating factor (DAF) and were then labeled with fluorescein isothio-cyanate-conjugated anti-mouse IgG. Cells were analyzed using a flow cytometer.The results demonstrate for the first time that CR3 and DAF are elevated on alveolar macrophages, and that MCP and DAF are increased on BALF lymphocytes in sarcoidosis. The possible roles of complement-related membrane proteins in the pathogenesis of immune processes that are ongoing in sarcoidosis are still obscure, but our results may provide some useful information on the mechanisms underlying sarcoidosis.

We present a lattice QCD study of the phase shift of $I{=}2$ $����$ scattering on the basis of two different approaches: the standard finite volume approach by Luscher and the recently introduced HAL QCD potential method. Quenched QCD simulations are performed on lattices with extents $N_s{=}16,24,32,48$ and $N_t{=}128$ as well as lattice spacing $a{\sim}0.115\,\mathrm{fm}$ and a pion mass of $m_��{\sim}940\,\mathrm{MeV}$. The phase shift and the scattering length are calculated in these two methods. In the potential method, the error is dominated by the systematic uncertainty associated with the violation of rotational symmetry due to finite lattice spacing. In Luscher's approach, such systematic uncertainty is difficult to be evaluated and thus is not included in this work. A systematic uncertainty attributed to the quenched approximation, however, is not evaluated in both methods. In case of the potential method, the phase shift can be calculated for arbitrary energies below the inelastic threshold. The energy dependence of the phase shift is also obtained from Luscher's method using different volumes and/or nonrest-frame extension of it. The results are found to agree well with the potential method., Version 2, consistent with published version

CD46, membrane cofactor protein, is a glycoprotein widely present on the cell membranes and is different in molecular weight among organs or cells in the same individual. It acts as a cofactor of I of the complement system, which inactivates C3b bound to the autologous cells, and protects them from the attack of the complement. In this study CD46 was demonstrated in the stomach immunochemically. Gastric CD46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of the vessels in the submucosal layer, whereas expressed weakly in the submucosa and muscle. Western blot analyses revealed that gastric CD46 was expressed as one broad band with molecular weight ranging from 60 kDa to 69 kDa, which was distinct from that of lymphocytes in the peripheral blood.

CD 46, membrane cofactor protein (MCP), is a membrane regulatory glycoprotein of the complement system, and acts as a cofactor of factor I, which inactivates C3b and C4b bound on autologous cell membrane. MCP is present on human peripheral blood cells except erythrocytes, fibroblasts, epithelial and endothelial cells, and has been proved to exist in other organs including gastrointestinal tract recently. In this study the expression and characterization of MCP on normal human colonic mucosa was investigated. Immunohistochemical study showed MCP in the colonic mucosal epithelium. Western blot analysis revealed that MCP protein was expressed as a broad band of 50-65 kDa in all cases and another faint band of 43-46 kDa in 3 out of 20 cases, though the latter band was highly suspected to be originated from contaminated mononuclear cells in the colon.

CD 46, membrane cofactor protein, is a membrane protein which shows different expression and phenotypes with the organ or cell in the same individual. Previously, we reported that gastric CD 46 was expressed strongly in the mucosal epithelium, mucosa and endothelial cells of vessels in the submucosal layer. Western blot analysis revealed that gastric CD 46 was expressed as one broad band with a molecular weight ranging from 60 kDa to 69 kDa, which was different from that of lymphocytes. In this study, we investigated the differences in expression and characterization of CD 46 in gastric cancer obtained by surgery as compared with non-cancerous mucosa. Expression of CD 46 was greater in gastric cancer than in non-cancerous mucosa. In some cases, the phenotypes of CD 46 in gastric cancer were different from those in the non-cancerous tissue.

We study the three nucleon force in the triton channel using dynamical clover fermion lattice QCD. The Nambu-Bethe-Salpeter wave function is utilized to obtain the potentials among three nucleons. Since the straightforward calculation is prohibitively expensive, two different frameworks are developed to meet the challenge. In the first method, we study the effective two nucleon potentials in the three nucleon system, where the differences between the effective two nucleon potentials and the genuine two nucleon potentials correspond to the three nucleon system effect, part of which is originated from the three nucleon force. The calculation is performed using Nf=2 clover fermion at m(\pi)= 1.13GeV generated by CP-PACS Collaboration, and Nf=2+1 clover fermion at m(\pi)= 0.70, 0.57GeV generated by PACS-CS Collaboration. In the second method, we study the three nucleon system with 3D-configuration of nucleons fixed. This enables us to extract the three nucleon force directly, if both of parity-even and parity-odd two nucleon potentials are provided. Since parity-odd two nucleon potentials are not available in lattice QCD at this moment, we propose a new general procedure to identify the three nucleon force using only parity-even two nucleon potentials. The calculation are performed with Nf=2 clover fermion at m(\pi)= 1.13GeV generated by CP-PACS Collaboration, employing the linear setup for the 3D-configuration. Preliminary results for the scalar/isoscalar three nucleon force are presented., Comment: Talk given at 28th International Symposium on Lattice Field Theory (Lattice 2010), Villasimius, Italy, 14-19 Jun 2010, 7 pages, 6 figures

Results are presented for the electromagnetic mass splittings of the low lying hadrons. These are used to determine the non-degenerate light quark masses. It is found that m_u=2.24(10)(34), m_d=4.65(15)(32), and $m_s=97.6(2.9)(5.5)$ MeV (MSbar scheme, 2 GeV scale). The first error is statistical and the second systematic. We find the lowest order electromagnetic splitting (m_pi+-m_pi0)_QED=3.38(23) MeV, the splittings including next-to-leading order, (m_pi+-m_pi0)_QED=4.50(23) MeV, (m_K+-m_K0)_QED=1.87(10) MeV, and the m_u != m_d contribution to the kaon mass difference, (m_K+-m_K0)_(m_u-m_d)=-5.840(96) MeV. All errors are statistical only, and the next-to-leading order pion splitting is only approximate; it does not contain all next-to-leading order contributions. We also computed the proton-neutron mass difference, including for the first time, QED interactions in a realistic 2+1 flavor calculation. We find $(m_p-m_n)_{\rm QED}=0.383(68)$ MeV, (m_p-m_n)_(m_u-m_d)=-2.51(14) MeV, and the total m_p-m_n=-2.13(16)(70) MeV, where the first error is statistical, and the second, part of the systematic error. We use domain wall fermions and the Iwasaki gauge action (gauge coupling beta=2.13). We use two lattice sizes, 16^3 and 24^3, to address finite volume effects. Non-compact QED is treated in the quenched approximation. We present new results for the electromagnetic low energy constants in SU(3) and SU(2) partially-quenched chiral perturbation theory to the next-to-leading order, obtained from fits to our data. Detailed analysis of systematic errors in our results and methods for improving them are discussed. Finally, new analytic results for SU(2)_L x SU(2)_R-plus-kaon chiral perturbation theory, including the one-loop logs proportional to alpha_em*m, are given., Comment: Significant additions: finite volume analysis of kaon mass (Sec. II and the Appendix) which is used to obtain new central values, extended discussion of the breaking of Dashen's theorem (VII), additional phenomenological results (VII), and a new section (VIII) on isospin breaking effects on the kaon decay constant. No conclusions or results from the first version changed significantly

免疫グロブリン(IG)療法の有する補体学的活性について検討するため,重症肺感染症患者11症例にのべ12回のIG療法を行い,末梢血の補体溶血活性,補体蛋白量,補体分解産物の変動を経時的に検討した. IG療法によりACH 50は低下し, C3, C9やB因子の蛋白量は減少した.またBbは早期に増加し, iC 3 bはこれに遅れて増加した. CH 50やC4dの変動は認められなかった.これらの事実より, IG療法には補体第2経路の活性化を充進させる作用があるものと考えられた.またIGには,直接的なB因子の活性化作用があることもin vitroの実験から示された.これらの現象から推定されるIGの有する生物学的作用は,補体系を介した効率的な抗菌作用の促進と補体活性の制御であろうが,同時に本研究で確認されたBb, iC 3 bと言った補体分解産物の有する生物学的活性に関する検討が重要と思われた.

びまん性汎細気管支炎(DPB) 3症例に対して延べ7回の免疫グロブリン(IG)療法を施行し,末梢血の血算や補体レセプターの変動を検討した.IG療法により赤血球は一過性に減少し,また治療前には著増していた単球や顆粒球の補体レセプターも減少した.赤血球の減少に対する確証は得られないが,肝脾など網内系での一過性捕捉が推定され,免疫複合体などのクリアランスが行われているものと推測された.単球膜表面CR 1, CR 2, CR 3と顆粒球膜表面CR 1の減少はそれぞれの血球膜上のC 3の増減をみないことから,この原因としてリガンド結合後に生じるinteriorizationやcappingによるレセプター性状の変化,あるいはレセプター自体の膜表面からの離脱が考えられ,同時にレセプターのregulation過剰亢進状態における膜表面へのレセプター補充の遅延があるものと考えられた.また症例によってはこれらのレセプターの減少に先立ち,短期間の間むしろレセプターが増加しており,補体レセプターはIG療法によりいったん増加した後減少している可能性が高いものと思われた.こうしたレセプターの増減が有する生物学的意義は,貪食細胞の機能亢進作用や,細胞内活性物質の遊離亢進作用であろうと考えられた.またIGの末梢血に対する直接的作用を検索するために,健常人のヘパリン化末梢血にIGを最終濃度3mg/mlとなるように添加し振盪加温した.その結果intact globulinおよびFc部分を欠くF (ab')2 globulinともに単球と顆粒球のCR 1を増加させ,単球のHLA・DRをも増加させた.またintact globulinは単球のIL-2レセプターを増加させ,リンパ球のHLA・DRを減少させた. DPBに対するIG療法には,補体系の関与したオプソニン効果の増強とともに,単球の活性化やリンパ球の抑制作用などの細胞性免疫にもなんらかの調節作用が存在するものと推定された.

補体系の動態をより詳細に評価するため,補体系活性化の過程で生じる分解産物(C4d, iC3b, Bb)を,結合織疾患患者において測定し,その臨床的有用性につき検討した.測定は各補体分解産物に対するモノクローナル抗体を用いたELISA法により行った.健常人に比しSLE, RAでは測定したすべての分解産物が, MCTDではC4d, iC3bが有意の高値を示した.またSLEでは溶血補体価(CH50)と各補体分解産物値は相関をせず, CH50高度低下群,正常群で分解産物の有意な高値を認めた.種々の結合織疾患においてC3, C4などの蛋白定量やCH50の測定が診断の一助となり,さらにSLEなどにおいては,疾患活動性の指標として利用される.しかしその一方で一部のSLEやRA, MCTDなどで痛感されるように,従来の補体系の検査は必ずしも補体系の動態を反映しているとは限らない.これら補体分解産物の測定は,従来の溶血補体活性とはまた違った意義があり,補体系の関与する病態解明へのアプローチに有用であると思われた.

We report a case of Churg-Strauss syndrome complaining of gross hematuria. A 74-year-old man was admitted to our hospital for further examination of gross hematuria. Abdominal CT and retrograde pyelography revealed left renal pelvic tumor, and left nephrectomy was performed. There was no tumor, but submucous hemorrhage was seen in the renal pelvis. The histopathologic diagnosis was allergic granulomatous angitis. The administration of prednisolone was done, but he suddenly died of acute heart failure after 1 month postoperatively.

An increase in glomerular size occurs in normal maturation after subtotal renal ablation and disease states such as diabetes mellitus. The role that growth hormone (GH), growth hormone releasing factor (GHRF), and insulinlike growth factor-1 (IGF-1) play in these processes has been investigated using transgenic mice chronically expressing these hormones. The glomeruli were enlarged in all 3 strains of mice. Mesangial proliferation followed by progressive glomerulosclerosis was observed in the GH and GHRF animals only. In the IGF-1 mice the large glomeruli remained morphologically normal except for the enlargement. These data suggest that the glomerulosclerosis was due, in part, to disordered mesangial cell growth in response to circulating GH. The mesangial lesions in mice with chronically high plasma GH levels mimicked those in human diabetes mellitus. These models provide a means to study the hormonal regulation of glomerular growth and the role that specific hormones might play in the pathogenesis of glomerulosclerosis.

In 2010, the Human Space Technology Initiative (HSTI) was launched by the United Nations Office for Outer Space Affairs (UNOOSA) within the United Nations Programme on Space Applications. The Initiative aims at promoting international cooperation in human spaceflight and space exploration-related activities, creating awareness among countries on the benefits of utilizing human space technology and its applications, and building capacity in microgravity education and research. HSTI has conducted a series of outreach activities and expert meetings bringing together participants from around the world. HSTI will also be implementing science and educational activities in relevant areas to raise the capacities, particularly in developing countries, in pursuit of the development goals of the United Nations, thus contributing to promoting the peaceful uses of outer space., Comment: 7 pages

The United Nations Human Space Technology Initiative (HSTI) aims at promoting international cooperation in human spaceflight and space exploration-related activities; creating awareness among countries on the benefits of utilizing human space technology and its applications; and building capacity in microgravity education and research. HSTI has been conducting various scientific activities to promote microgravity education and research. The primary science activity is called 'Zero-gravity Instrument Distribution Project', in which one-axis clinostats will be distributed worldwide. The distribution project will provide unique opportunities for students and researchers to observe the growth of indigenous plants in their countries in a simulated microgravity condition and is expected to create a huge dataset of plant species with their responses to gravity., Comment: 8 pages. arXiv admin note: text overlap with arXiv:1210.4797

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/m2 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 cut-off 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

Background Metastatic gastric cancer and cancer of the esophagogastric junction (GC/EGJ) is an aggressive disease with poor prognosis. In the TAGS study, trifluridine/tipiracil (FTD/TPI) improved overall survival (OS) compared with placebo in heavily pre-treated patients. This unplanned, exploratory subgroup analysis of the TAGS study aimed to clarify outcomes when FTD/TPI was used as third-line (3L) treatment and fourth- or later-line (4L+) treatment. Patients and methods Patients were divided into a 3L group (126 and 64 in FTD/TPI and placebo arms, respectively) and 4L+ group (211 and 106 in FTD/TPI and placebo arms, respectively). Endpoints included OS, progression-free survival (PFS), time to Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration to ≥2, and safety. Results Baseline characteristics were generally well balanced between FTD/TPI and placebo for 3L and 4L+ treatment. Median OS (mOS) for FTD/TPI versus placebo was: 6.8 versus 3.2 months {hazard ratio (HR) [95% confidence interval (CI)] = 0.68 (0.47-0.97), P = 0.0318} in the 3L group; and 5.2 versus 3.7 months [0.73 (0.55-0.95), P = 0.0192] in the 4L+ group. Median PFS for FTD/TPI versus placebo was 3.1 versus 1.9 months [0.54 (0.38-0.77), P = 0.0004] in the 3L group; and 1.9 versus 1.8 months [0.57 (0.44-0.74), P < 0.0001] in the 4L+ group. Time to deterioration of ECOG PS to ≥2 for FTD/TPI versus placebo was 4.8 versus 2.0 months [HR (95% CI) = 0.60 (0.42-0.86), P = 0.0049] in the 3L group; and 4.0 versus 2.5 months [0.75 (0.57-0.98), P = 0.0329] in the 4L+ group. The safety of FTD/TPI was consistent in all subgroups. Conclusions This analysis confirms the efficacy and safety of FTD/TPI in patients with GC/EGJ in third and later lines with a survival benefit that seems slightly superior in 3L treatment. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide patients with an mOS of 6.8 months., Highlights • The TAGS study included patients with GC/EGJ receiving FTD/TPI as 3L and 4L+ treatment. • Improved mOS with FTD/TPI versus placebo led to international guidance to use FTD/TPI as 3L treatment. • This analysis showed a potential differential benefit in OS with FTD/TPI versus placebo in 3L or 4L+ treatment. • Safety was consistent in all subgroups and quality of life was maintained in all patients during the study. • Findings clarify outcomes that physicians can expect when prescribing FTD/TPI according to international guidelines.