Trial in Progress: A Perspective Study of Pan-Oral Triplet Regimen Pomalidomide, Ixazomib and Dexamethasone in Relapsed or Refractory Myeloma Patients

Abstract Background ： During the past decade, bortezomib, lenalidomide and dexamethasone (VRd) followed by lenalidomide maintenance has become one of the most effective first-line regimens in multiple myeloma (MM) and been recommended by many guidelines. However, when disease relapses after VRd induction and lenalidomide maintenance, further generation of proteasome inhibitors or immunomodulator drugs, or agents with different mechanism should be considered. Pomalidomide, a new-generation oral immunomodulator drug, can overcome lenalidomide resistance and has better efficacy and safety in MM patients. Pomalidomide has a synergistic effect with proteasome inhibitor and dexamethasone, which has been proved more effective than pomalidomide and dexamethasone dual-drug regimen in relapsed or refractory MM (RRMM) patients (Richardson, et al. Lancet Oncol 2019). The overall response rate (ORR) of lenalidomide retreatment is only 54% (Sumit, et al. Blood 2011). A convenient and safe pan-oral regimen, ixazomib, pomalidomide and dexamethasone (IxaPd) is expected to improve the efficacy and survival in RRMM patients. The purpose of this study is to evaluate the efficacy and safety of IxaPd regimen in RRMM patients who have received lenalidomide in China. Study Design and Methods: This multi-center open-label, single-arm study (NCT04989140) will enroll patients with measurable M protein who have received 1 to 3 prior lines of therapy (including lenalidomide) with documented disease progression during or after their most recent treatment. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, expected overall survival (OS) ≥3 months, and who provide informed consent will be eligible. Patients with prior exposure to pomalidomide, ixazomib and those intolerant/refractory to bortezomib will be excluded. Eligible 60 patients will be enrolled in this IxaPD regimen. Clinical and laboratory parameters will be recorded at baseline. Cytogenetic abnormalities are tested via fluorescence in situ hybridization (FISH) in CD138 sorted myeloma cells. Ixazomib 4 mg on days 1, 8 and 15 every 28 days, pomalidomide 4mg qd day 1-21 every 28-day, dexamethasone 40 mg (20 mg for patients >75 years of age) every week will be administrated. Treatment will continue until disease progression or unacceptable toxicity. Drug doses will be adjusted or withdrawn according to the degree of toxicities. The primary endpoint is progression free survival (PFS), the secondary endpoints include OS, time to next treatment (TTNT), ORR, safety. Patients are stratified into subpopulation on the basis of cytogenetic abnormalities, prior treatment lines and exposure drugs, ect. PFS, OS and TTNT were analyzed by Kaplan-Meier survival plot. Response will be evaluated according to International Myeloma Working Group (IMWG) 2016 criteria, and done at baseline and each cycle from 1-5, then every other cycle till cycle 13, and every three cycles till cycle 28 if the subjects do not relapse. Patients who reach complete response (CR) need to perform a minimal residual disease (MRD) test via next-generation flow (NGF) . Conclusion: This is the first prospective clinical study to examine the efficacy and safety of pan-oral IxaPd regimen for RRMM in Chinese patients. Disclosures Research sponsor: CHIATAI TIANQING PHARMACEUTICAL GROUP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Pomalidomide, Bortezomib, and Dexamethasone (PVd) for Chinese Multiple Myeloma Patients at First Relapse

Blood ◽

10.1182/blood-2021-147749 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4781-4781

Author(s):

Lugui Qiu ◽

Gang An

Keyword(s):

Multiple Myeloma ◽

Peripheral Neuropathy ◽

Group Performance ◽

Conflicts Of Interest ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Chinese Patients ◽

Kaplan Meier ◽

First Relapse ◽

Grade 3

Abstract Background: The phase 3 OPTIMISMM（NCT01734928） trial done at 133 hospitals and research centres in 21 countries but no Chinese site involved in this study. In the OPTIMISMM study ,pomalidomide, bortezomib, and dexamethasone (PVd) demonstrated excellent efﬁcacy in patients at ﬁrst relapse, including immediately after upfront lenalidomide treatment failure and other common ﬁrst-line treatments, the mPFS was 20.73 months, the ORR was 90.1%, and no new safety signals were observed. Building on these promising results, we decided to explore PVd in Chinese patients at ﬁrst relapse. Study Design/Methods: This is a multicenter, prospective, single-arm phase 2 study designed to evaluate the efﬁcacy and safety of PVd in Chinese patients at ﬁrst relapse. Eligible patients were aged ≥18 years and had a diagnosis of multiple myeloma, measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were required to have had only 1 prior antimyeloma regimen. Key exclusion criteria included creatinine clearance<30 mL/min requiring dialysis, grade ≥3 peripheral neuropathy, or grade 2 peripheral neuropathy with pain. Patients with prior exposure to bortezomib were eligible, provided they were not refractory to a bortezomib-containing regimen dosed at 1.3 mg/m 2 twice weekly. Patient（n=62,Figure 1）will receive pomalidomide 4 mg on days 1-14 of each cycle. Bortezomib 1.3 mg/m 2 on days 1, 4, 8, and 11 of cycles 1-8 and on days 1 and 8 of cycles 9 and beyond. Dexamethasone was given on days 1, 2, 4, 5, 8, 9, 11, and 12 of cycles 1-8 and on days 1, 2, 8, and 9 of cycles 9 and beyond; patients received 20 mg of dexamethasone if aged ≤75 years and 10 mg otherwise. The primary endpoint is ORR, the secondary endpoints are≥VGPR, MRD(-) rate, PFS, OS and safety. ORR will be assessed by the International Myeloma Working Group criteria after each cycle until PD. The Kaplan-Meier method will be used to estimate PFS and OS. Safety analysis will be conducted in the safety population, which are composed of all patients who received ≥1 dose of study medication. The trial is currently enrolling and will be open in 7 sites of China. Disclosures: Research Sponsor: CHIATAI TIANQING PHARMACEUTICAL GROUP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

Blood Advances ◽

10.1182/bloodadvances.2019000010 ◽

2019 ◽

Vol 3 (12) ◽

pp. 1815-1825 ◽

Cited By ~ 4

Author(s):

M. O’Dwyer ◽

R. Henderson ◽

S. D. Naicker ◽

M. R. Cahill ◽

P. Murphy ◽

...

Keyword(s):

Partial Response ◽

Group Performance ◽

Residual Disease ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Staging System ◽

Complete Response ◽

Weekly Schedule ◽

Intention To Treat ◽

Good Partial Response

Abstract Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

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Cohort compassionate-use program (CUP) and early access program (EAP) with cabazitaxel (Cbz) plus prednisone (P; Cbz + P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D): Analysis by age group.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.109 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 109-109

Author(s):

Zafar Malik ◽

Giuseppe di Lorenzo ◽

Sergio Bracarda ◽

Alexandros Ardavanis ◽

Mert Basaran ◽

...

Keyword(s):

Disease Progression ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Age Groups ◽

Phase Iii ◽

World Population ◽

Age Group ◽

Castration Resistant Prostate Cancer ◽

Grade 3

109 Background: Cbz + P demonstrated an overall survival benefit vs mitoxantrone + P in pts with mCRPC in the Phase III TROPIC trial. The CUP (CABAZ_C_05005) and EAP (NCT01254279) (both funded by Sanofi) were established to allow access to Cbz ahead of commercial availability. The programs are also evaluating Cbz safety in a real-world population. Data analyzed by age group (≤75 and >75 years) are presented here. Methods: Expected enrolment across both programs is 1,450 pts from 236 centres worldwide. Pts received Cbz 25 mg/m2 IV Q3W + P 10 mg QD until disease progression, death, unacceptable toxicity or physician/pt decision. G-CSF is administered as per ASCO guidelines. Results: As of May 30, 2012, 1,301 pts have enrolled (≤75 years: 1,061 pts [81.6%]; >75 years: 240 pts [18.4%]). Eastern Cooperative Oncology Group performance status and incidence of visceral metastases were generally balanced between treatment groups. The most frequent reasons for discontinuation were disease progression (46.8%) followed by adverse events (AEs; 24.4%) in pts ≤75 years, and AEs (36.4%) followed by disease progression (31.1%) in pts >75 years. Time from initial diagnosis to inclusion was greater in pts >75 years (median 79.66 months) than in pts ≤75 years (median 53.94 months), but time from mCRPC diagnosis to inclusion was approximately equivalent (>75 years: median 22.6 months; ≤75 years: median 20.94 months). G-CSF use was more frequent in pts >75 years (cycle 1: 62.9% of pts) compared with pts ≤75 years (cycle 1: 52.2% of pts). AEs of clinical concern were more frequent in the older age group (Grade ≥3 AEs: >75 years 64.2%; ≤75 years 54.8%). Grade ≥3 neutropenia was observed in 25.8% of pts >75 years and in 17.0% of pts ≤75 years. Conclusions: We observed several differences between age groups in baseline and on-treatment parameters, suggesting differences in the natural history of mCRPC (faster disease progression in pts ≤75 years than in pts >75 years) and secondary to treatment (AEs more frequent in pts >75 years compared with pts ≤75 years). Clinical trial information: NCT01254279.

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Randomized Trial Comparing Pomalidomide, Bortezomib, and Dexamethasone (PVd) Versus Bortezomib and Dexamethasone（Vd） in NDMM with Renal Impairment（RI）

Blood ◽

10.1182/blood-2021-146914 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1660-1660

Author(s):

Jian Hou

Keyword(s):

Multiple Myeloma ◽

Renal Function ◽

Renal Impairment ◽

Creatinine Clearance ◽

Group Performance ◽

Conflicts Of Interest ◽

Eastern Cooperative Oncology Group ◽

Phase 2 ◽

Efficacy And Safety ◽

Renal Response

Abstract Background: RI is one of the most common complications of multiple myeloma (MM). The incidence of RI at diagnosis ranges from 20% to 50%, Bortezomib-based regimens remain the cornerstone of the management of myeloma-related RI, and the addition of a third drug to Vd seems to be beneﬁcial，but not for sure. Pomalidomide is extensively metabolized by liver, with only approximately 2% of active substance eliminated in the urine, which suggests that RI may not affect pomalidomide exposure in a clinically relevant manner. The MM013(phase 2, NCT02045017) trial confirmed that Pomalidomide could be safely used in RRMM with RI and achieved good response in MM and Renal function. The OPTIMISMM (phase 3, NCT01734928) trial Subgroup analysis reported efficacy and safety of PVd vs Vd at first relapse by renal function (creatinine clearance [CrCl] < 60 vs ≥ 60 mL/min) before. The ORR significantly improved with PVd vs Vd regardless of renal status (P < .001 for both renal groups): 91.4% vs 53.6% (≥ VGPR,54.3% vs 21.4%) in the CrCl < 60 mL/min group and 89.5% vs 55.2% (≥ VGPR, 64.5% vs 23.0%) in the CrCl ≥ 60 mL/min group. Since RVd is the standard treatment for NDMM patients, We believe that standard dose Pomalidomide plus Vd will be very promising for NDMM patients with RI Study Design/ Methods: This is a multicenter, prospective, randomized phase 2 study designed to evaluate the efﬁcacy and safety of PVd Versus Vd in Patients With NDMM and Renal Impairment（RI）. Eligible patients were aged ≥18 years and had a diagnosis of multiple myeloma, measurable disease, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were required to have had no prior antimyeloma regimen. The deﬁnition of RI is based on reduced creatinine clearance (15 mL/min≤CrCl＜60 mL/min) without indication for hemodialysis, which have to be the result of myeloma. Key exclusion criteria included previous course of chemotherapy; uncontrolled malignant disorder, infection, or peripheral neuropathy, patients on dialysis will be excluded too. Approximately 79 patients will be randomized 2:1(Figure 1) to Arm A (PVd) or Arm B (Vd), both Arms will have induction therapy for 4 cycles. In Arm A, patients will receive pomalidomide 4 mg on days 1-14 of each cycle. Bortezomib 1.3 mg/m 2 on days 1, 4, 8, and 11 of each cycle. Dexamethasone 20mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (21-day cycles); In Arm B, patients will receive the same bortezomib and dexamethasone as Arm A. The primary endpoint is ≥VGPR, the secondary endpoints are MRD(-) rate,renal response,Immune function,Renal tubular function, and safety. Myeloma response and renal response will be assessed by the International Myeloma Working Group criteria after each cycle. Eficacy analyses will be performed on the intent-to-treat population; Safety analysis will be conducted in the safety population, which are composed of all patients who received ≥1 dose of study medication. The trial is currently enrolling and will be open in 8 sites in China. Disclosure：Research Sponsor : CHIATAI TIANQING PHARMACEUTICAL GROUP. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Pomalidomide which was approved in RRMM will be used in NDMM with RI

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Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

Leukemia ◽

10.1038/s41375-021-01488-8 ◽

2022 ◽

Author(s):

Thierry Facon ◽

Gordon Cook ◽

Saad Z. Usmani ◽

Cyrille Hulin ◽

Shaji Kumar ◽

...

Keyword(s):

Multiple Myeloma ◽

Subgroup Analysis ◽

Group Performance ◽

Residual Disease ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Newly Diagnosed ◽

Frailty Status ◽

Frail Patients

AbstractIn the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n = 368; Rd, n = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P < 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P = 0.003). Improved rates of complete response or better and minimal residual disease (10–5) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.

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A preliminary study of apatinib in Chinese patients with osteosarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e22500 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e22500-e22500 ◽

Cited By ~ 2

Author(s):

Yong Zhou ◽

Fan Tang ◽

Li Min ◽

Wenli Zhang ◽

Rui Shi ◽

...

Keyword(s):

Safety Profile ◽

Kinase Inhibitor ◽

Group Performance ◽

Pulmonary Metastases ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Chinese Patients ◽

First Line

e22500 Background: Osteosarcoma is the most common malignant tumor of bone that displays hyperproliferative characteristics and high vascularity, making vascular endothelial growth factor receptors (VEGFRs) become promising targets. Apatinib, a tyrosine kinase inhibitor targeting VEGFR-2, shows anti-cancer effects against a broad range of malignancies. This study reported the clinical experience of apatinib in osteosarcoma. Methods: We collected the medical data of osteosarcoma cases who received apatinib for at least one month in our hospital. The objective response rate (ORR), disease control rate (DCR), and 6-month progression-free survival (PFS) and overall survival (OS) rates were evaluated, and the safety profile was observed. The cut-off date of analysis was 01/17/2017. Results: Between May 2015 and Nov 2016, a total of 34 cases received apatinib with informed consent (4 as neoadjuvant, 1 as neoadjuvant and first line, 10 as first line, 15 as second line and 4 as third line). Among them, 18 (52.9%) cases suffered from pulmonary metastases before apatinib administration; 29 (85.3%) patients had an Eastern Cooperative Oncology Group performance status of 1–2. Initial dosages of 250, 425, and 500 mg/d were given to 5 (14.7%), 3 (8.8%), and 26 (76.5%) cases, respectively. Dosage adjustment occurred in only 8 (23.5%) patients. The median duration was 5.9 months (95%CI, 4.5–9.4 months). According to RECIST v1.1, complete response, partial response, stable disease and progressive disease were achieved in 1 (2.9%), 6 (17.6%), 25 (73.5%) and 2 (5.9%) patients, respectively. The ORR was 20.5%, and the DCR was 94.1%. Patients with pulmonary metastases showed a relatively better response to apatinib, as the ORR and DCR were 33.3% and 88.9%, respectively. As for safety analysis, the most 3 common adverse events (AEs) were hand-foot syndrome (HFS) (29, 85.3%), diarrhea (16, 47.1%), and decreased appetite (9, 26.5%). Nine grade III AEs were occurred including 3 HFS, 2 hypertension, 1 diarrhea, 1 oral mucositis, 1 proteinuria and 1 serious peeling. Conclusions: Apatinib seems to be effective in treating osteosarcoma with acceptable safety profile. Perspective clinical studies with adequate sample size are required to validate our results.

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Preoperative prediction of suboptimal resection in advanced ovarian cancer based on clinical and CT parameters

Acta Radiologica ◽

10.1177/0284185116658683 ◽

2016 ◽

Vol 58 (4) ◽

pp. 498-504 ◽

Cited By ~ 4

Author(s):

Hye Min Son ◽

See Hyung Kim ◽

Bo Ra Kwon ◽

Mi Jeong Kim ◽

Chan Sun Kim ◽

...

Keyword(s):

Ovarian Cancer ◽

Logistic Regression ◽

Group Performance ◽

Residual Disease ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Advanced Ovarian Cancer ◽

Cox Proportional Hazards Model ◽

Validation Dataset ◽

Predictive Values

Background Cytoreduction is important as a survival predictor in advanced ovarian cancer. Purpose To determine the prediction of suboptimal resection (SOR) in advanced ovarian cancer based on clinical and computed tomography (CT) parameters. Material and Methods Between 2007 and 2015, 327 consecutive patients with FIGO stage III–IV ovarian cancer and preoperative CT were included. During 2007–2012, patients were assigned to a derivation dataset ( n = 220) and the others were assigned to a validation dataset ( n = 107). Clinical parameters were reviewed and two radiologists assessed the presence or absence of tabulated parameters on CT images. Logistic regression analyses based on area under the receiver-operating characteristic curve (AUROC) were performed to identify variables predicting SOR, and generated simple score using Cox proportional hazards model. Results There was no statistical difference in patients’ characteristics in both datasets, except for residual disease ( P = 0.001). Optimal resection improved from 45.0% (99/220) in the derivation dataset to 64.4% (69/107) in the validation dataset. Logistic regression identified that Eastern Cooperative Oncology Group-performance status (ECOG-PS 2), involvements of peritoneum, diaphragm, bowel mesentery and suprarenal lymph nodes, and pleural effusion were independent variables of SOR. Overall AUROC for score predicting SOR was 0.761 with sensitivity, specificity, and positive and negative predictive values of 70.6%, 73.2%, 68.7%, and 91.9%, respectively. In the derivation dataset, AUROC was 0.792, with sensitivity of 71.4% and specificity of 74.3%, and AUROC of 0.758 with sensitivity of 69.2% and specificity of 72.8% in the validation dataset. Conclusion CT may be a useful preoperative predictor of SOR in advanced ovarian cancer.

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Myosteatosis as a novel prognostic biomarker after radical cystectomy for bladder cancer

Scientific Reports ◽

10.1038/s41598-020-79340-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Shimpei Yamashita ◽

Yuya Iwahashi ◽

Haruka Miyai ◽

Takashi Iguchi ◽

Hiroyuki Koike ◽

...

Keyword(s):

Bladder Cancer ◽

Radical Cystectomy ◽

Cox Regression ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Psoas Muscle ◽

Hounsfield Units ◽

Computed Tomography Images ◽

Psoas Muscles

AbstractThis study aims to evaluate the influence of myosteatosis on survival of patients after radical cystectomy (RC) for bladder cancer. We retrospectively identified 230 patients who underwent RC for bladder cancer at our three institutions between 2009 and 2018. Digitized free-hand outlines of the left and right psoas muscles were made on axial non-contrast computed tomography images at level L3. To assess myosteatosis, average total psoas density (ATPD) in Hounsfield Units (HU) was also calculated as an average of bilateral psoas muscle density. We compared cancer-specific survival (CSS) between high ATPD and low ATPD groups and performed cox regression hazard analyses to identify the predictors of CSS. Median ATPD was 44 HU (quartile: 39–47 Hounsfield Units). Two-year CSS rate in overall patients was 76.6%. Patients with low ATPD (< 44 HU) had significantly lower CSS rate (P = 0.01) than patients with high ATPD (≥ 44 HU). According to multivariate analysis, significant independent predictors of poor CSS were: Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.03), decreasing ATPD (P = 0.03), non-urothelial carcinoma (P = 0.01), pT ≥ 3 (P < 0.01), and pN positive (P < 0.01). In conclusion, myosteatosis (low ATPD) could be a novel predictor of prognosis after RC for bladder cancer.

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Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Cancers ◽

10.3390/cancers13061388 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1388

Author(s):

Manlio Mencoboni ◽

Marcello Ceppi ◽

Marco Bruzzone ◽

Paola Taveggia ◽

Alessia Cavo ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Group Performance ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Small Cell ◽

Small Cell Lung ◽

Eligibility Criteria

Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs. We performed a systematic review and a meta-analysis to evaluate the effectiveness and safety of these drugs, and more generally of ICIs, as second-line therapy in NSCLC patients in real world practice. MEDLINE, PubMed, Scopus and Web of Science were searched to include original studies published between January 2015 and April 2020. A total of 32 studies was included in the meta-analysis. The overall radiological response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were 21%, 52%, 3.35 months and 9.98 months, respectively. The results did not change when analysis was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) and age. A unitary increase in the percent of patients with liver and CNS metastases reduced the occurrence of DCR by 7% (p < 0.001) and the median PFS by 2% (p = 0.010), respectively. The meta-analysis showed that the efficacy and safety of immunotherapy in everyday practice is comparable to that in clinical trials.

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Definitive carbon ion radiotherapy for tracheobronchial adenoid cystic carcinoma: a preliminary report

BMC Cancer ◽

10.1186/s12885-021-08493-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jian Chen ◽

Jingfang Mao ◽

Ningyi Ma ◽

Kai-Liang Wu ◽

Jiade Lu ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Group Performance ◽

Primary Tumour ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Tumour Response ◽

Carbon Ion Radiotherapy ◽

Rare Tumour ◽

Carbon Ion ◽

Adenoid Cystic

Abstract Background Tracheobronchial adenoid cystic carcinoma (TACC) is a rare tumour. About one-third of patients miss their chance of surgery or complete resection as it is mostly detected in the advanced stage; hence, photon radiotherapy (RT) is used. However, the outcomes of photon RT remain unsatisfactory. Carbon ion radiotherapy (CIRT) is thought to improve the therapeutic gain ratio; however, the outcomes of CIRT in TACC are unclear. Therefore, we aimed to assess the effects and toxicities of CIRT in patients with TACC. Methods The inclusion criteria were as follows: 1) age 18–80 years; 2) Eastern Cooperative Oncology Group Performance Status 0–2; 3) histologically confirmed TACC; 4) stage III–IV disease; 5) visible primary tumour; and 6) no previous RT history. The planned prescription doses of CIRT were 66–72.6 GyE/22–23 fractions. The rates of overall survival (OS), local control (LC), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Treatment-induced toxicities and tumour response were scored according to the Common Terminology Criteria for Adverse Events and Response Evaluation Criteria in Solid Tumors, respectively. Results Eighteen patients with a median age of 48 (range 30–73) years were enrolled. The median follow-up time was 20.7 (range 5.8–44.1) months. The overall response rate was 88.2%. Five patients developed lung metastasis after 12.2–41.0 months and one of them experienced local recurrence at 31.9 months after CIRT. The rates of 2-year OS, LC, and PFS were 100, 100, and 61.4%, respectively. Except for one patient who experienced grade 4 tracheal stenosis, which was relieved after stent implantation, no other ≥3 grade toxicities were observed. Conclusions CIRT might be safe and effective in the management of TACC based on a short observation period. Further studies with more cases and longer observation are warranted.

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