265
Background: Despite the difficulty of directly comparing trastuzumab deruxtecan (T-DXd) and nivolumab as third- or later-line treatment for HER2-positive advanced gastric cancer (AGC) in ...randomized trials, discussions regarding optimal treatment strategies are desired. Methods: This single-institution retrospective study aimed to describe the real-world efficacy and safety of T-DXd and nivolumab as third- or later-line treatment for patients with HER2-positive AGC treated between March 2016 and May 2022. Results: Overall, 58 patients (median age, 64 years; 69% male) were eligible (T-DXd group, n = 20; nivolumab group, n = 38). Most had HER2 3+ (72%) and presented with metastatic disease at diagnosis (66%). Response rates in the 41 patients with measurable lesions were 50% and 15% in the T-DXd and nivolumab groups, respectively. The T-DXd and nivolumab groups had a median progression-free survival of 4.8 months (95% confidence interval CI, 3.3–7.0) and 2.3 months (95% CI, 1.5–3.5), median overall survival of 10.8 months (95% CI, 6.9–23.8) and 11.7 months (95% CI, 7.6–17.1), and grade 3 or greater adverse event rates of 50% and 2%, respectively. Overall, 64% received subsequent treatment. Among 23 patients who received both regimens, the T-DXd–nivolumab and nivolumab–T-DXd groups had a median overall survival of 14.0 months (95% CI, 5.0–not reached) and 19.3 months (95% CI, 9.5–25.1), respectively. Conclusions: T-DXd and nivolumab had distinctive efficacy and toxicity profiles as third- or later-line treatment for HER2-positive AGC. Considering the distinct features of each regimen might help clinicians personalize the optimal treatment approaches for patients with HER2-positive AGC.
93
Background: The prostaglandin E
2
-EP4 signaling is involved in immunosuppression in cancers. In the dose escalation part of the ONO-4578-01, open-label, uncontrolled phase 1 study, ONO-4578, an ...EP4 antagonist, plus nivolumab (4578+NIV) demonstrated manageable safety profile and antitumor activities in metastatic or advanced solid tumors. CRC cohort assessed safety, preliminary efficacy, and biomarkers of 4578+NIV in patients with metastatic colorectal cancer (mCRC). Methods: The CRC cohort was conducted at 12 sites in Japan and it included patients aged ≥20 years with mCRC; those with microsatellite-instability-high, deficient mismatch repair, or BRAF mutations were excluded. The optimal dose was determined based on the results of dose escalation part of ONO-4578-01. Patients received oral ONO-4578 (40 mg, daily) and intravenous nivolumab (480 mg, every 4 weeks) in 28-day cycles. The primary endpoint was safety. Exploratory endpoints included efficacy and biomarkers. Results: A total of 51 patients were enrolled: 24 (47.1%) were male and the median age was 59.0 (range, 33–79) years. Adverse events (AEs) occurred in 48 patients (94.1%), wherein grade 3–4 AEs occurred in 23 (45.1%). No patients died due to AEs. Serious AEs occurred in 11 (21.6%) patients. The most common AEs of any grade were rash (33.3%) and anemia (31.4%). Any-grade and grade ≥3 treatment-related AEs (TRAEs) occurred in 36 (70.6%) and 13 (25.5%) patients, respectively. Two patients achieved partial response and 18 had stable disease; the objective response rate was 3.9% (90% confidence interval CI, 0.7–11.8) and the disease control rate was 39.2% (90% CI, 27.7–51.7). The median progression-free survival and overall survival (OS) were 1.54 (90% CI, 1.41–2.79) and 10.68 months (90% CI, 6.67–not reached NR), respectively. The proportion of patients continuing treatment and OS in subgroups of different PD-L1 combined positive scores (CPS) showed a tendency toward favorable efficacy in CPS-positive subgroups: the proportion of patients continuing treatment for 6 months was 4.5% (1/22) in those with CPS of 0 vs 20% (5/25) in those with CPS ≥1, and the median OS was 9.4 months (90% CI, 5.65–12.06) in those with CPS of 0 vs NR (90% CI, 10.41–NR) in those with CPS ≥1. Conclusions: 4578+NIV showed an acceptable safety profile in patients with mCRC, and no new safety signals were detected. 4578+NIV also showed antitumor activity in patients with mCRC. Favorable efficacy was observed in the PD-L1 CPS-positive subpopulation. Clinical trial information: jRCT2080223441 .
Abstract
We fabricated (Ph
4
P)
2
ZnCl
4
and (Ph
4
P)
2
ZnBr
4
crystals (Ph
4
P: tetraphenylphosphonium) with zero-dimensional structures via solvent evaporation and evaluated their optical and ...scintillation properties. Fluorescence and phosphorescence peaks derived from Ph
4
P
+
cations appeared at 345 and 510 nm, respectively, for both crystals, while an emission originating from self-trapped excitons was also detected for (Ph
4
P)
2
ZnBr
4
. In the scintillation spectra, both samples exhibited a phosphorescence peak, while a weak fluorescence peak was also observed for (Ph
4
P)
2
ZnCl
4
. In addition, the scintillation light yield (LY) was determined by pulse-height spectra with 1
μ
s shaping time. A pulse-height peak was observed from (Ph
4
P)
2
ZnCl
4
, and the scintillation LY was about 670 photons/5.5 MeV-
α
, which was higher than that of a ZnO single crystal.
Abstract
Y
2
SiO
5
(YSO) single crystals with various Ce concentrations were fabricated and their photoluminescence (PL) and optically stimulated luminescence (OSL) properties analyzed. From the ...evaluation of PL properties, there was an emission band centered at 420 nm in Ce:YSO samples. The observed emission originated from the 5d-4f transitions of Ce
3+
ions. In OSL properties, OSL spectra under stimulation at 520 nm exhibited emission peaks at 420 nm, and the emission origin was also the 5d-4f transitions of Ce
3+
ions. The OSL dose response functions had a lower detection limit of 1 mGy for the 0.5 and 1.0% Ce:YSO samples, and 10 mGy for the 0.1 and 2.0% Ce: YSO samples. The OSL intensity of the 1.0% Ce:YSO sample was approximately 69.3% after 24 h from X-ray irradiation compared to immediately after X-ray irradiation.
Eulytite-type Ba
RE(PO
)
(RE = Y, La, and Lu) single crystals were synthesized by the floating zone method, and their scintillation properties were investigated. The powder X-ray diffraction ...measurement revealed that the single phase of Ba
RE(PO
)
samples were successfully synthesized. The samples exhibited a luminescence peak due to self-trapped exciton at around 400 nm under vacuum ultraviolet and X-ray irradiation. The X-ray-induced scintillation decay time constants of the samples were several microseconds at room temperature. In the
Am α-ray irradiated pulse height spectra, all the samples showed a clear full energy peak, and the absolute light yields of the Ba
Y(PO
)
, Ba
La(PO
)
, and Ba
Lu(PO
)
single crystals were estimated to be 960, 1160, and 1220 ph/5.5 MeV-α, with a typical error of ±10%, respectively. The scintillation light yields of the Ba
RE(PO
)
have been quantitatively clarified for the first time.
There are no optimal indication criteria for neoadjuvant chemotherapy (NAC) in patients with resectable colorectal liver metastases (CLM). The aim of this study was to prospectively assess the ...survival benefit of selective NAC administration in this patient population based on tumor characteristics.
Borderline resectable CLM (BR-CLM) were defined as four or more liver metastases, CLM larger than 5 cm, or CLM with concomitant resectable extrahepatic metastases. From 2010 to 2015, NAC was administered to BR-CLM patients. Upfront surgery without NAC was performed to patients having clearly resectable CLM (less than 3 lesions, smaller than 5 cm, and no extrahepatic metastases: CR-US group). Survival outcomes of the two groups were assessed.
The BR-NAC group comprised 73 patients and the CR-US group 172. All patients in the BR-NAC group underwent subsequent resection, as none showed disease progression or chemotherapy-associated liver damage. The 3- and 5-year overall survival rates of the CR-US group were 83.0% and 74.0%, while patients in the BR-NAC group had comparable 3-year and 5-year overall survivals (80.5% and 66.6%, P = 0.397).
Defining BR-CLM based on tumor characteristics optimizes patient selection for NAC. Favorable overall survival can be achieved by upfront surgery in patients with clearly resectable CLM and by NAC in patients with BR-CLM.
T-cell lymphoma is a rare hematologic malignancy with an incidence rate between 10% and 20% of that of non-Hodgkin lymphomas. Patients with peripheral T-cell lymphoma (PTCL) generally have a poor ...prognosis when treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP)/CHOP-like chemotherapy; once relapse occurs, it is mostly regarded as an incurable disease. To overcome the chemorefractoriness of PTCL, several novel agents have been developed. Since the first approval of pralatrexate, a dihydrofolate reductase inhibitor, for relapsed/refractory PTCL by the US Food and Drug Administration, several new agents, such as romidepsin (histone deacetylase inhibitor), brentuximab vedotin (antibody-drug conjugate targeting CD30), chidamide (histone deacetylase inhibitor), and mogamulizumab (anti-CC chemokine receptor 4 monoclonal antibody), have been approved as a therapeutic option for relapsed/refractory PTCL in several countries, including the US, Europe, China, and Japan. Forodesine is a novel, potent purine nucleoside phosphorylase inhibitor that is effective against T-cell malignancies. Although the clinical development of forodesine was discontinued in the US and Europe, a multicenter Phase I/II study of oral forodesine for relapsed PTCL was recently completed in Japan. The overall response rate was 24% (10 of 41 patients), which included four patients with complete response. In general, the toxicity of forodesine is manageable. As the study met the primary end point, forodesine was approved for the treatment of relapsed/refractory PTCL in Japan in March 2017, which was the first approval of forodesine in the world. As forodesine is an oral formulation, it is more convenient than other novel intravenous agents approved for PTCL. However, it is necessary to appropriately manage opportunistic infections and secondary lymphomas possibly associated with long-lasting lymphocytopenia caused by forodesine. In this manuscript, we have summarized the currently available evidence for forodesine and discussed the clinical implications for PTCL treatment.
Eulytite-type Basub.3RE(POsub.4)sub.3 (RE = Y, La, and Lu) single crystals were synthesized by the floating zone method, and their scintillation properties were investigated. The powder X-ray ...diffraction measurement revealed that the single phase of Basub.3RE(POsub.4)sub.3 samples were successfully synthesized. The samples exhibited a luminescence peak due to self-trapped exciton at around 400 nm under vacuum ultraviolet and X-ray irradiation. The X-ray-induced scintillation decay time constants of the samples were several microseconds at room temperature. In the sup.241Am α-ray irradiated pulse height spectra, all the samples showed a clear full energy peak, and the absolute light yields of the Basub.3Y(POsub.4)sub.3, Basub.3La(POsub.4)sub.3, and Basub.3Lu(POsub.4)sub.3 single crystals were estimated to be 960, 1160, and 1220 ph/5.5 MeV-α, with a typical error of ±10%, respectively. The scintillation light yields of the Basub.3RE(POsub.4)sub.3 have been quantitatively clarified for the first time.
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of clinically aggressive diseases associated with poor outcome. Studies that focus specifically on PTCL are emerging, with the ultimate ...goal of improved understanding of disease biology and the development of more effective therapies. However, one of the difficulties in classifying and studying treatment options in clinical trials is the rarity of these subtypes. Various groups have developed lymphoma classifications over the years, including the World Health Organization, which updated its classification in 2008. This article briefly reviews the major lymphoma classification schema, highlights contributions made by the collaborative International PTCL Project, discusses prognostic issues and gene expression profiling, and outlines therapeutic approaches to PTCL. These include the standard chemotherapeutic regimens and other modalities incorporating antifolates, conjugates, histone deacetylase inhibitors, monoclonal antibodies, nucleoside analogs, proteasome inhibitors, and signaling inhibitors. As this review emphasizes, the problem has now evolved into an abundance of drugs and too few patients available to test them. Collaborative groups will aid in future efforts to find the best treatment strategies to improve the outcome for patients with PTCL.
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