12-month Overall Survival Research Articles

CT-098 Impact of T-Cell Dose on Outcome of T Cell–Replete HLA-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation

The outcome of allogeneic hematopoietic cell transplantation (HCST) relies on both disease-related factors and transplant-related factors including the conditioning regimen and immunotherapy exploiting the graft-versus-tumor (GVT) effect. CD3+ T cells are the main player in the GVT process, but an increased dose of these cells results in an increased risk of acute graft-versus-host disease (GVHD). We aimed to study whether the T-cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes in our patient population. This is a retrospective chart review study including patients over 18 years of age, diagnosed with AML, ALL, or MDS, who underwent PBSC mismatched allogeneic transplant, including haploidentical, one-antigen mismatched related, or 2-alleles mismatched related transplants at the King Hussein Cancer Center's bone marrow transplant program between January 2010 and December 2020. We calculated the median CD3 cell dose and divided all patients into 2 groups (Low and High dose groups) and then measured the cumulative incidence of acute GVHD, chronic GVHD, and 1- and 2-year overall survival (OS). Thirty-five patients were stratified according to the median CD3+ cell dose into the Low CD3 group, which included 18 (51%) patients with a mean dose of 13.7×107/kg (range: 2.8-19.7), and the High CD3 group, which included 17 (49%) patients with a mean dose of 29.7×107/kg (range: 19.8-93.1) (P-value: 0.000). The cumulative incidence of acute GVHD was 60% (n=12) in the Low CD3 group and 40% (n=8) in the High CD3 group (P-value: 0.24). The cumulative incidence of chronic GVHD was 64% (n=9) in the Low CD3 group and 35% (n=5) in the High CD3 group (P-value: 0.26). The overall survival for the cohort (n=35) at 12 months was 60.9% and reached 49.6% at 24 months. The 12-month OS for the Low and High CD3 groups was 66.7% and 52.9%, respectively. The 24-month OS for the Low and High CD3 groups was 66.7% and 33.1%, respectively (P-value: 0.084). Although the study showed a trend toward better OS in the Low CD3+ dose group, the difference was not statistically significant.

MM-233 Evaluation of the Comparative Effectiveness of In-Class Transition (iCT) to All-Oral Ixazomib-Lenalidomide-Dexamethasone (IRd) After Bortezomib (V)-Based Induction Therapy vs Patients Who Continued to Receive Parenteral V-Based Therapy in Newly Diagnosed Multiple Myeloma (NDMM)

Increasing the duration of proteasome inhibitor-based treatment could improve outcomes in NDMM patients. To evaluate the comparative effectiveness of in-class transition (iCT) to IRd following V-based induction vs continued V-based therapy. A secondary analysis of patients from US MM-6, (NCT03173092; Manda CLML 2020; phase IV, single-arm study) which is evaluating iCT from parenteral V to all-oral IRd ('IRd' cohort), and a comparator ('V-based') cohort of patients from INSIGHT MM (Costello Future Onc 2019; prospective, observational study) who continued to receive V-based therapy. Routine community clinical practice in the US. Non-transplant-eligible NDMM patients with ≥stable disease after 3 cycles of V-based induction and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 from US MM-6 (IRd cohort, n=100) and INSIGHT MM (V-based cohort, n=111). First-line duration of treatment (DOT), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and reasons for treatment discontinuation. Kaplan-Meier methodology was used for time-to-event outcomes. To reduce imbalances between cohorts, inverse probability of treatment weighting (IPTW) was used. Results are presented as IRd vs V-based cohorts. After IPTW, median age was 75.0 vs 74.8 years; 56.7 vs 51.3% of patients were male, 37.4 vs 29.1% had ECOG PS of 2, and 48.8 vs 41.4% were International Staging System stage III at diagnosis. Initial induction therapy was VRd/V-cyclophosphamide (C)-d/VRCd in 79.5/17.7/2.8 vs 77.3/19.5/3.1% of patients. ORRs were 73.2 (95% confidence interval [CI]: 65.0-81.3) vs 57.5% (95% CI: 47.9-67.1; p<0.0001). Median DOT was 10.8 (95% CI: 6.5-24.4) vs 5.3 months (95% CI: 4.3-7.0; p<0.0001; median follow-up, 20.3 vs 15.8 months). Median PFS and OS were not estimable in either cohort. 24-month PFS rates were 85.7 (95% CI: 68.1-94.0) vs 76.5% (95% CI: 62.6-85.8). 24-month OS rates were 94.0 (95% CI: 77.7-98.5) vs 84.9% (95% CI: 70.6-92.6). Overall, 17.6% discontinued IRd and 24.4% discontinued V due to an adverse event. In NDMM patients treated at US community oncology clinics, those who transitioned to IRd following 3 cycles of V-based induction had significantly higher ORR and longer DOT than those who continued to receive V-based therapy.

S1173 Terlipressin Treatment of Patients With Hepatorenal Syndrome Type 1 Decreased the Need for Renal Replacement Therapy in Transplant Recipients: A 12-Month Follow-Up of the CONFIRM Study

Introduction: Hepatorenal syndrome type 1 (HRS) is a rapid-onset renal failure in the setting of end-stage liver disease. While liver transplant (LT) is the definitive treatment, posttransplant renal failure requiring renal replacement therapy (RRT) is common and contributes to low patient survival rates. A randomized, placebo (PBO)-controlled study (CONFIRM; NCT02770716) demonstrated that terlipressin (TERLI) reversed HRS and reduced the need for RRT. This subgroup analysis of LT recipients from CONFIRM assessed whether TERLI treatment reduced the incidence of RRT and improved overall survival (OS) through 12-months posttransplant. Methods: Patients with HRS were treated with TERLI plus albumin (n=199) or PBO plus albumin (n=101) for up to 14 days. RRT was defined as any procedure that replaced nonendocrine kidney function including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques. The incidence of verified HRS reversal (primary endpoint in CONFIRM), HRS reversal, the need for RRT (pretransplant; at Day 180 and Day 365 posttransplant), and OS at 12-months were compared between groups. Verified HRS reversal was defined as the percentage of patients with 2 consecutive qualified serum creatinine (SCr) values of ≤1.5 mg/dL at least 2 hours apart. HRS reversal was defined as the percentage of patients with a SCr value of ≤1.5 mg/dL while receiving treatment by Day 14 or day of discharge. Results: In total, 46 (23%) patients in the TERLI group and 29 (28%) patients in the PBO group received an LT (P=.290). Five of these patients (TERLI n=3; PBO n=2) received a simultaneous liver–kidney transplant. Verified HRS reversal was comparable between the TERLI group (30%, n=14) and the PBO group (17%, n=5; P=.168). HRS reversal was significantly higher in the TERLI group (37%, n=17) vs the PBO group (14%, n=4; P=.021). The pretransplant need for RRT was significantly lower in the TERLI group compared with PBO (P=.007; Figure). The posttransplant need for RRT was significantly lower in the TERLI vs PBO group at Day 180 (P=.017; Figure) and Day 365 (P=.009; Figure). Posttransplant 12-month OS in the TERLI group was 94% (n=43) compared with 83% (n=24) in the PBO group (P=.093). Conclusion: Patients with HRS who received TERLI treatment and an LT had a decreased need for RRT for up to 12-months posttransplant. These findings have implications for morbidity and mortality in patients with advanced cirrhosis.Figure 1.: Incidence of RRT by Treatment Group in Transplant Recipients in the CONFIRM Study, ITT population. Values at the bottom of each bar represent n/N. ITT, intent-to-treat; n, number of patients requiring RRT; N, number of patients who were alive at each timepoint; RRT, renal replacement therapy.

Lanreotide Depot to Treat Gastroenteropancreatic Neuroendocrine Tumors in a US Community Oncology Setting: A Prospective, Observational Study.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) can result in symptoms such as diarrhea, flushing, abdominal pain, and fatigue and are often associated with a significant disease burden and poor prognosis. This non-interventional, prospective, observational study evaluated the real-world safety and effectiveness of lanreotide depot, a somatostatin analog (SSA) used to treat GEP-NETs, in a community setting. In this prospective, non-interventional study (NCT02730104), adult patients with locally advanced (inoperable), metastatic GEP-NETs treated with lanreotide depot were evaluated by their physician every 6 months from enrollment for 24months. Clinically defined time to disease progression (TTDP) and overall survival (OS) were estimated for the total population and by primary tumor type (gastrointestinal [GI], pancreatic, unknown origin), and an exploratory analysis determined the rate of progression-free survival (PFS) at 12 and 24months. Patient satisfaction was evaluated via the Treatment Satisfaction Questionnaire for Medication (TSQM-9), and safety information was recorded. Of 99 patients, the 24-month PFS rate was 73.7% (95% confidence interval [CI] 63.1-81.7) and 24-month OS rate was 84.2% (95% CI 74.0-90.7). Median TTDP was not reached because few patients experienced disease progression during the study period. The majority of responding patients expressed satisfaction with treatment on each domain of the TSQM-9. Treatment-related adverse events (AEs) occurred in 19.2% of patients, while no serious AEs (SAEs) were related to the study drug. Lanreotide depot is an effective and well-tolerated treatment for GEP-NETs in the real-world community setting. ClinicalTrials.gov identifier, NCT02730104.

Dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation–positive hairy cell leukemia

AbstractBRAF V600E is the key oncogenic driver mutation in hairy cell leukemia (HCL). We report the efficacy and safety of dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600E mutation–positive HCL. This open-label, phase 2 study enrolled patients with BRAF V600E mutation–positive HCL refractory to first-line treatment with a purine analog or relapsed after ≥2 prior lines of treatment. Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed objective response rate (ORR) per criteria adapted from National Comprehensive Cancer Network-Consensus Resolution guidelines. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Fifty-five patients with BRAF V600E mutation–positive HCL were enrolled. The investigator-assessed ORR was 89.0% (95% confidence interval, 77.8%-95.9%); 65.5% of patients had a complete response (without minimal residual disease [MRD]: 9.1% [negative immunohistochemistry of bone marrow {BM} biopsy], 12.7% [negative BM aspirate flow cytometry {FC}], 16.4% [negative immunohistochemistry and/or FC results]; with MRD, 49.1%), and 23.6% had a partial response. The 24-month DOR was 97.7% with 24-month PFS and OS rates of 94.4% and 94.5%, respectively. The most common treatment-related adverse events were pyrexia (58.2%), chills (47.3%), and hyperglycemia (40.0%). Dabrafenib plus trametinib demonstrated durable responses with a manageable safety profile consistent with previous observations in other indications and should be considered as a rituximab-free therapeutic option for patients with relapsed/refractory BRAF V600E mutation–positive HCL. This trial is registered at www.clinicaltrials.gov as #NCT02034110.

Outcomes After Nonresponse and Relapse Post-Tisagenlecleucel in Children, Adolescents, and Young Adults With B-Cell Acute Lymphoblastic Leukemia.

Nonresponse and relapse after CD19-chimeric antigen receptor (CAR) T-cell therapy continue to challenge survival outcomes. Phase II landmark data from the ELIANA trial demonstrated nonresponse and relapse rates of 14.5% and 28%, respectively, whereas use in the real-world setting showed nonresponse and relapse rates of 15% and 37%. Outcome analyses describing fate after post-CAR nonresponse and relapse remain limited. Here, we aim to establish survival outcomes after nonresponse and both CD19+ and CD19- relapses and explore treatment variables associated with inferior survival. We conducted a retrospective multi-institutional study of 80 children and young adults with B-cell acute lymphoblastic leukemia experiencing nonresponse (n = 23) or relapse (n = 57) after tisagenlecleucel. We analyze associations between baseline characteristics and these outcomes and establish survival rates and salvage approaches. The overall survival (OS) at 12 months was 19% across nonresponders (n = 23; 95% CI, 7 to 50). Ninety-five percent of patients with nonresponse had high preinfusion disease burden. Among 156 morphologic responders, the cumulative incidence of relapse was 37% (95% CI, 30 to 47) at 12 months (CD19+; 21% [15 to 29], CD19-; 16% [11 to 24], median follow-up; 380 days). Across 57 patients experiencing relapse, the OS was 52% (95% CI, 38 to 71) at 12 months after time of relapse. Notably, CD19- relapse was associated with significantly decreased OS as compared with patients who relapsed with conserved CD19 expression (CD19- 12-month OS; 30% [14 to 66], CD19+ 12-month OS; 68% [49 to 92], P = .0068). Inotuzumab, CAR reinfusion, and chemotherapy were used as postrelapse salvage therapy with greatest frequency, yet high variability in treatment sequencing and responses limits efficacy analysis across salvage approaches. We describe poor survival across patients experiencing nonresponse to tisagenlecleucel. In the post-tisagenlecleucel relapse setting, patients can be salvaged; however, CD19- relapse is distinctly associated with decreased survival outcomes.

1019P Pattern of clinical activity of anticancer vaccine OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in phase III Atalante-1 randomized trial

OSE2101 (Tedopi) is an anticancer vaccine increasing overall survival (OS) with HR of 0.59 (p=0.017) versus Standard of Care Chemotherapy (SoC CT) in the population of interest (PoI) of HLA-A2+ NSCLC patients with IO secondary resistance after sequential CT-IO (ESMO 2021 #47LBA). The objective of this analysis was to explore the pattern of activity of OSE2101. 118 NSCLC EGFR and ALK negative patients were randomized (2:1) in OSE2101 or SoC (docetaxel or pemetrexed) in the PoI. OS of OSE2101 versus SoC was described according to best response (partial response (PR), Stable Disease (SD) and Progressive Disease (PD)) and to the administration of post progression anticancer treatment. OS was described in Late Progressors (LP) defined as no RECIST 1.1 nor clinical PD within the first 6 months after randomization. Median (95%CI) OS in months by best response and by post progression anticancer treatment are described in the table. 16 (20%) patients fulfilled the criteria for Late Progressors with OSE2101. Late Progressors included 4 (25%) patients with PR and 12 (75%) patients with prolonged SD. mOS was 14.7 months with 1-year OS rate of 68%. mPFS was 8.8 months with 23% of patients progression-free at 1-year.Table: 1019PmOS (months)OSE2101 n=80SoC n=38By Best ResponsePRn=6 11.2 (5.4, NE)n=7 13.8 (2.6, NE)HR=0.75 (0.18, 3.23)SDn=36 13.1 (8.8, 16.8)n=19 9.4 (6.5, 12.2)HR=0.61 (0.33, 1.14)PDn=32 8.0 (5.4, 11.1)n=7 5.0 (1.0, 7.2)HR=0.45 (0.19, 1.04)By Post Progression anticancer treatmentWith anticancer treatmentn=55 13.5 (9.6,16.6)n=16 10.6 (7.2, 16.1)HR=0.71 (0.38, 1.30)Without anticancer treatmentn=25 6.3 (3.6, 7.6)n=22 4.5 (2.3, 8.3)HR=0.76 (0.41, 1.41) Open table in a new tab In advanced HLA-A2+ NSCLC patients with IO secondary resistance after sequential CT-IO, OS was longer with OSE2101 versus SoC regardless the use of post progression anticancer treatment. By Best Response to study treatement, OS was longer with OSE2101 in patients with Stable Disease or Progressive Disease compared to SoC. Late progressors with OSE2101 were mainly driven by long Stable Disease. These data suggest that the cancer vaccine OSE2101 may act as an anti-tumor brake in controlling the tumor growth regardless of best response.

667P Updated efficacy and safety of larotrectinib in patients with TRK fusion salivary gland tumours

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers of various tumour types, including salivary gland tumours (SGTs). Secretory carcinoma of the salivary gland, a rare subset of SGTs, is characterised by an ETV6-NTRK3 gene fusion found in ≥80% of cases. Larotrectinib is a highly selective, central nervous system-active, tropomyosin receptor kinase (TRK) inhibitor with an objective response rate (ORR) of 92% across 24 evaluable patients (pts) with a variety of SGTs, as of July 2020 (Le et al. Oncologist 2022 [in press]). We report updated efficacy and safety of larotrectinib in pts with TRK fusion SGTs with longer follow-up. Pts with TRK fusion SGTs were identified from two larotrectinib clinical trials (NCT02122913, NCT02576431). Pts received larotrectinib 100 mg twice a day (BID) except for one pt who received 150 mg BID in the phase 1 trial (NCT02122913). Response was assessed by independent review committee (per Response Evaluation Criteria in Solid Tumours v1.1). As of July 2021, 25 pts with TRK fusion SGTs were identified, including 24 with an additional year of follow-up. Median age was 59.0 years (range 28–80). All pts had ETV6-NTRK3 gene fusions. ORR was 84% (95% CI 64–95%): 8 complete responses, 13 partial responses, 2 stable disease and 2 progressive disease. Median time to response was 1.8 months. Median duration of response (DoR) was not reached; median follow-up was 39.6 months. Median progression-free survival (PFS) was 56.0 months (95% CI 30.8–not estimable) at a median follow-up of 41.3 months. Median overall survival (OS) was not reached at a median follow-up of 43.7 months. The 36-month DoR, PFS, and OS rates were 71%, 64%, and 82%. Duration of treatment ranged from 1.0 to 68.0 months. At data cut-off, 8 pts had progressed, with 5 pts continuing treatment post-progression for ≥4 weeks. Treatment-related adverse events (TRAEs) were mostly Grade 1–2. Grade 3–4 TRAEs were reported in 6 pts (24%). There were no treatment discontinuations due to TRAEs. Larotrectinib demonstrated rapid and durable efficacy with a favourable safety profile in pts with TRK fusion SGTs. These data highlight the importance of identifying NTRK gene fusions in pts with SGTs.

Treatment Outcome and Safety of the TCX Regimen for Advanced Gastric Cancer: A Prospective Cohort Study.

ObjectiveTo evaluate the outcome and safety of the paclitaxel, carboplatin, and capecitabine (TCX) regimen in patients with advanced gastric cancer.MethodsAdvanced gastric cancer patients received the TCX regimen for up to six cycles, which were 3 weeks apart. Paclitaxel (175 mg/m2) was given over a 3-hour infusion, followed by carboplatin in a 1-hour infusion on day 1. Capecitabine (850 mg/m2) was given orally twice daily from day 1 to day 14. Primary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsAmong 83 patients at stage IVa and IVb, the median PFS was 9.3 months; 6-month, 1-year, and 2-year PFS were 74.6%, 32.5%, and 14.4%, respectively. The median OS was 17.0 months; 6-month, 1-year, and 2-year OS were 97.5%, 68.7%, and 21.7%, respectively. In the multivariable Cox regression model, higher CEA was associated with poor OS. Common adverse events included hand-food syndrome (77.9%), peripheral neuropathy (63.2%), fatigue (68.7%), and nausea (54.2%).ConclusionThe TCX regimen provided good survival and a better safety profile. More clinical trials are needed to confirm its treatment efficacy and safety, especially in comparison with other triplet regimens.

Efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory soft tissue sarcoma: a multicenter, phase 2 trial.

BackgroundAnti-angiogenic agents have been reported to exert promising clinical activity for advanced soft tissue sarcoma (STS). Apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, is effective and safe for various solid tumors, but its role in STS remains unclear. The aim of this study was to explore the efficacy and safety of apatinib in patients with untreated or chemotherapy-refractory STS.MethodsIn this multicenter, single-arm, phase 2 trial, patients aged 18–70 years with untreated or chemotherapy-refractory STS were enrolled and received 500 mg apatinib per day. During treatment, patients were followed up with imaging every 8 weeks. The primary endpoint was the 6-month progression-free survival (PFS) rate. The secondary endpoints were objective response rate (ORR), overall survival (OS), and adverse events (AEs), which were graded following the National Cancer Institute common terminology criteria for AEs version 4.03.ResultsFrom June 2017 to October 2018, 53 patients were enrolled, 51 of whom received at least one dose of apatinib. Of the 53 patients, 41 (77.4%) had chemotherapy-refractory disease. The median follow-up was 13.3 months. The 6- and 12-month PFS rates were 46.8% and 25.2%, respectively, with a median PFS of 5.6 months [95% confidence interval (CI): 3.8–9.2 months]. The median PFS was 5.5 months for chemotherapy-refractory patients, 9.1 months for untreated patients, 13.9 months for patients with alveolar soft part sarcoma (ASPS), and 3.7 months for patients with clear cell sarcoma (CCS). The 12- and 24-month OS rates were 58.6% and 44.9%, respectively, with a median OS of 20.0 months (95% CI: 9.2–31.1 months). The median OS was 10.7 months for chemotherapy-refractory patients and not estimated for untreated, ASPS, nor CCS patients. In 50 evaluable patients, the ORR was 18.0% and the disease control rate was 86.0%. These results were similar to those of the per-protocol set. The most common grade 3 or 4 AEs included hypertension [30 (58.8%) of 51 patients], leukopenia [12 (23.5%)], proteinuria [8 (15.69%)], and hematuria [8 (15.69%)]. One patient died of unknown cause.ConclusionsThis study suggested that apatinib might be effective and tolerable in patients with untreated or chemotherapy-refractory STS (NCT03064243).

EP08.01-087 First-Line Pembrolizumab-Combination Therapy for Advanced Squamous NSCLC: Real-World Outcomes at US Oncology Practices

In KEYNOTE-407, median overall survival (OS) was 17.1 months (95% CI, 14.4-19.9); 12- and 24-month OS rates were 64.7% and 37.5%, respectively; and median duration of exposure was 7.1 months (range, 0.03-26.3) for patients with metastatic squamous NSCLC treated with first-line pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel (pembrolizumab-chemotherapy). This study aimed to examine real-world time on treatment (rwToT) and OS among patients with advanced squamous NSCLC treated with first-line pembrolizumab-chemotherapy at US oncology practices.

Brigatinib in Japanese patients with tyrosine kinase inhibitor-naive ALK-positive non-small cell lung cancer: first results from the phase 2 J-ALTA study

BackgroundWe evaluated the safety and efficacy of the anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) brigatinib in Japanese patients with TKI-naive ALK-positive non-small cell lung cancer (NSCLC) from the phase 2, open-label, single-arm, multicenter J-ALTA study.MethodsIn the TKI-naive cohort of J-ALTA, the primary end point was independent review committee (IRC)-assessed 12-month progression-free survival (PFS). Secondary end points included objective response rate (ORR), intracranial response, overall survival (OS), and safety.ResultsThe data were cut approximately 12 months after last patient enrollment. Thirty-two patients with ALK TKI-naive ALK-positive NSCLC were enrolled (median age [range], 60.5 [29–85] years; median duration of follow-up, 14.2 [3.2–19.3] months; median treatment duration, 13.8 [0.4–19.3] months). IRC-assessed 12-month PFS was 93.0% (90% confidence interval (CI) 79.2–97.8%); ORR, 96.9% (95% CI 83.8–99.9%), 12-month OS, 96.9% (95% CI 79.8–99.6%), and median OS was not reached. Of five patients with measurable baseline CNS metastases, two had partial intracranial response. The most common treatment-emergent adverse events were increased blood creatine phosphokinase (81%), hypertension (59%), and diarrhea (47%). Grade ≥ 3 adverse events occurred in 91% of patients; pneumonitis was reported in 3 (9%) patients.ConclusionsIn the J-ALTA TKI-naive cohort, brigatinib demonstrated clinically meaningful efficacy consistent with the international phase 3 study. The safety profile in Japanese patients was consistent with previous studies. Brigatinib is an important first-line option for Japanese patients with ALK-positive NSCLC.Clinical registrationNCT03410108

Apatinib for recurrent/progressive glioblastoma multiforme: A salvage option

Purpose: The recurrent/progressive glioblastoma multiforme (GBM) carries a dismal prognosis and the definitive treatment strategy has not yet been established. This study aimed to assess the efficacy and safety of apatinib in recurrent/progressive GBM patients. Materials and methods: The clinical data of 19 recurrent/progressive GBM patients who received apatinib treatment from November 2015 to December 2019 at Sun Yat-sen University Cancer Center were collected retrospectively in this study. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were reviewed and assessed. Results: The overall ORR was 52.6%, and the DCR was 73.7%. Median PFS and OS were 5.1 and 10.4 months, respectively. The 6-month PFS and OS rates were 38.9% and 68.4%, respectively. The 12-month PFS and OS rates were 16.7% and 36.8%, respectively. The treatment-related toxicities were generally well-tolerated. The most common grade 3/4 AEs were hand-foot syndrome (36.8%) and hypertension (21.1%). Conclusion: Our study showed that apatinib therapy provided a better salvaging option for recurrent/progressive GBM patients and the toxicity was manageable.

Feasibility of Cyclosporine Prophylaxis Withdrawal in Critically Ill Allogenic Hematopoietic Stem Cell Transplant Patients Admitted to the Intensive Care Unit With No GVHD

Twenty percent of allogenic hematopoietic stem cell transplantation (allo-HSCT) patients require intensive care unit (ICU) admission. Feasibility and long-term consequences of cyclosporine graft-versus-host disease (GVHD) prophylaxis withdrawal in the ICU are unknown. To assess the impact of cyclosporine prophylaxis withdrawal in critically ill allo-HSCT patients admitted to the ICU on GVHD incidence and to evaluate 6-month overall survival according to cyclosporine withdrawal and GVHD occurrence. From 2010 to 2020, 101 critically ill allo-HSCT patients admitted to the ICU in our institution were included. All received cyclosporine as GVHD prophylaxis. None of them had GVHD at ICU admission. Patients were admitted in the ICU after a median time of 11 days (5.5-18) after allo-HSCT. ICU, hospital mortality, and 6-month mortality were 43.6%, 56.4%, and 59.4%, respectively. Cyclosporine was withdrawn for 52 and continued for 49 patients in the ICU. A total of 38.6% (n=39) developed secondarily acute GVHD (aGVHD) after a median of 28 days (15-40) after cyclosporine was discontinued. In 74.4% (n=29) of cases, patients in the hematology ward developed aGVHD after ICU discharge. Cyclosporine dosages were similar in both groups. Factors independently associated with aGVHD occurrence in multivariate analysis were cyclosporine withdrawal in the ICU (subdistribution hazard ratios [sHR]=2.04, 95% confidence interval [CI]=1.02-4.1, P=.044), renal replacement therapy (RRT) (sHR=0.43, 95% CI=0.19-0.9, P=.03) and fungal prophylaxis (sHR=2.62, 95% CI=1.35-5.07, P=.004). Cyclosporine withdrawal in the ICU was associated with poorer 6-month overall survival (OS) (HR=1.96, 95% CI=1.16-3.33, P=.012), but after adjusting on severity (simplified acute physiology score, vasopressors, mechanical ventilation and RRT requirement), 6-month OS did not differ (HR=1.35, 95% CI=0.76-2.42, P=.30). GVHD occurrence after ICU stay was significantly associated with better 6-month OS in unadjusted (HR=0.53, 95% CI=0.31-0.90, P=.02) and severity-adjusted analysis (HR=0.54, 95% CI=0.31-0.93, P=.028). Cyclosporine prophylaxis withdrawal in critically ill allo-HSCT patients in the ICU appears to be feasible and did not impair long-term outcome.

Diagnostic and prognostic nomograms for newly diagnosed intrahepatic cholangiocarcinoma with brain metastasis: A population-based analysis.

Brain metastasis (BM) is one of the rare metastatic sites of intrahepatic cholangiocarcinoma (ICC). ICC with BM can seriously affect the quality of life of patients and lead to a poor prognosis. The aim of this study was to establish two nomograms to estimate the risk of BM in ICC patients and the prognosis of ICC patients with BM. Data on 19,166 individuals diagnosed with ICC were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent risk factors and prognostic factors were identified by the logistic and the Cox regression, respectively. Next, two nomograms were developed, and their discrimination was estimated by concordance index (C-index) and calibration plots, while the clinical benefits of the prognostic nomogram were evaluated using the receiver operating characteristic (ROC) curves, the decision curve analysis (DCA), and the Kaplan-Meier analyses. The independent risk factors for BM were T stage, N stage, surgery, alpha-fetoprotein (AFP) level, and tumor size. T stage, surgery, radiotherapy, and bone metastasis were prognostic factors for overall survival (OS). For the prognostic nomogram, the C-index was 0.759 (95% confidence interval (CI) = 0.745-0.773) and 0.764 (95% CI = 0.747-0.781) in the training and the validation cohort, respectively. The calibration curves revealed a robust agreement between predictions and actual observations probability. The area under curves (AUCs) for the 3-, 6-, and 9-month OS were 0.721, 0.727, and 0.790 in the training cohort and 0.702, 0.777, and 0.853 in the validation cohort, respectively. The DCA curves yielded remarkable positive net benefits over a wide range of threshold probabilities. The Kaplan-Meier analysis illustrated that the nomogram could significantly distinguish the population with different survival risks. We successfully established the two nomograms for predicting the incidence of BM and the prognosis of ICC patients with BM, which may assist clinicians in choosing more effective treatment strategies.

3.0-T closed MR-guided microwave ablation for HCC located under the hepatic dome: a single-center experience

Purpose To analyze the clinical safety and efficacy of 3.0-T closed MR-guided microwave ablation (MWA) for the treatment of HCC located under the hepatic dome. Methods From May 2018 to October 2020, 49 patients with 74 HCCs located under the hepatic dome underwent MWA using 3.0-T closed MR guidance. The technical success rate, operative time, complete ablation (CA) rate, complications, local tumor progression (LTP), tumor-free survival (TFS) and overall survival (OS) were examined. Routine blood analysis, liver/kidney function and alpha fetoprotein (AFP) and protein induced by vitamin k absent or antagonist (PIVKA) levels were compared before and 2 months after MWA. Results All patients underwent MWA successfully, including 10 patients who underwent general anesthesia. The technical success rate was 100% without major complications. The CA rate was 95.9% (71/74) at the 2-month evaluation. The LTP rate was 2.7% during the median follow-up of 17.8 months (range: 4–43 months); the 6-, 12-, 18-month TFS rates were 97.8, 90.6, 68.1%, respectively, and the 6-, 12-, 18-month OS rates were 100, 97.6, 92.1%, respectively. There were no significant changes in routine blood tests and liver/kidney function (p > 0.05), while the AFP and PIVKA level decreased significantly at 2 months (p < 0.05). Conclusion 3.0-T MR-guided MWA is safe and feasible for HCC lesions located under the hepatic dome.

First-Line Pembrolizumab Monotherapy for Advanced NSCLC With Programmed Death-Ligand 1 Expression Greater Than or Equal to 50%: Real-World Study Including Older Patients in Japan

IntroductionPembrolizumab became available in Japan in February 2017 for first-line monotherapy of unresectable advanced and metastatic NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. This retrospective chart review study aimed to describe real-world clinical outcomes of first-line pembrolizumab monotherapy, including for patients 75 years or older, who are under-represented in clinical trials. MethodsWe identified patients (≥20 y old) at 23 sites initiating first-line pembrolizumab monotherapy from July 1, 2017, to December 20, 2018, for stages IIIB, IIIC, and IV NSCLC with PD-L1 TPS greater than or equal to 50% and Eastern Cooperative Oncology Group performance status of 0 to 2 or unknown. Patients with actionable genomic alterations (EGFR, ALK, ROS1, BRAF) and clinical trial participants were excluded. Time-to-event outcomes were estimated using Kaplan-Meier, with data cutoff on September 30, 2019. ResultsOf 441 eligible patients (78% men), 303 (69%) were younger than 75 years and 138 (31%) were 75 years or older; median age was 70 years. With median follow-up of 13.5 months, median overall survival (OS) was not reached (NR); 12- and 24-month OS rates were 72% and 58%, respectively. For ages younger than 75 and 75 years or older, median OS was NR and 23.5 months (95% confidence interval: 16.2–NR), respectively; 12-month OS rates were 74% and 67% and 24-month OS rates were 62% and 48%, respectively. Median real-world progression-free survival was similar in the two age groups (10.1 and 9.5 mo, respectively), as was median real-world time on treatment with pembrolizumab (5.7 and 5.6 mo). ConclusionsThese findings complement clinical trial results, adding real-world evidence supporting benefits of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 TPS greater than or equal to 50%, including for patients 75 years or older.

Bevacizumab combined with re-irradiation in recurrent glioblastoma.

BackgroundGlioblastoma is characterized by rich vasculature and abnormal vascular structure and function. Currently, there is no standard treatment for recurrent glioblastoma (rGBM). Bevacizumab (BEV) has established role of inhibiting neovascularization, alleviating hypoxia in the tumor area and activating the immune microenvironment. BEV may exert synergistic effects with re-irradiation (re-RT) to improve the tumor microenvironment for rGBM.PurposeThe purpose of this study was to evaluate the safety, tolerability, and efficacy of a combination of BEV and re-RT for rGBM treatment.MethodsIn this retrospective study, a total of 26 rGBM patients with surgical pathologically confirmed glioblastoma and at least one event of recurrence were enrolled. All patients were treated with re-RT in combination with BEV. BEV was administered until progression or serious adverse events.ResultsMedian follow-up was 21.9 months for all patients, whereas median progression-free survival (PFS) was 8.0 months (95% confidence interval [CI]: 6.5–9.5 months). In addition, the 6-month and 1-year PFS rates were 65.4% and 28.2%, respectively. The median overall survival (OS), 6-month OS rate, and 1-year OS rate were 13.6 months (95% CI: 10.2–17.0 months), 92.3%, and 67.5%, respectively. The patient showed good tolerance during the treatment with no grade > 3 grade side event and radiation necrosis occurrence rate of 0%. Combined treatment of gross total resection (GTR) before re-RT and concurrent temozolomide during re-RT was an independent prognostic factor that affected both OS and PFS in the whole cohort (OS: 0.067, 95% CI: 0.009–0.521, p = 0.010; PFS: 0.238, 95% CI: 0.076–0.744, p = 0.038).ConclusionIn this study, re-RT combined with concurrent and maintenance BEV treatment was safe, tolerable, and effective in rGBM patients. Moreover, GTR before re-RT and selective concurrent temozolomide could further improve patient PFS and OS.

The Prognostic Value of Baseline Clinical and Radiologic Imaging Features in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab.

PurposeTo identify prognostic clinical and radiologic features in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab.Patients and MethodsClinical and imaging records of patients with unresectable HCC were retrospectively reviewed, and baseline features were recorded. Patients’ records and imaging studies were used to determine the patients’ overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were performed to determine prognostic features. Subanalyses of treatment-naïve patients (who never received local or systemic therapy) and previously treated patients were also performed.ResultsFifty-five patients were included in the final analysis, 23 (41.8%) of whom were treatment naïve. The median PFS and OS for the entire cohort were 3.0 months and 7.9 months. The 3-, 6- and 12-month OS rates were 85.5%, 79.8% and 45.7%, respectively. The 3-, 6- and 12-month PFS rates were 50.1%, 41.2% and 20.1%, respectively. On multivariate analysis, independent prognostic features for poor PFS of the entire cohort were pleural effusions (p = 0.047, HR: 6.3; CI: 1.03–38.90) and hepatic vein tumor thrombus (p = 0.005; HR: 23.37; CI: 2.63–207.67); independent prognostic features for poor OS were ascites (p = 0.008; HR: 37.37; CI: 2.53–467.64), pleural effusion (p = 0.003; HR: 110.17; CI: 5.00–2426.54), and low (<40HU) pre-contrast attenuation on CT images (p = 0.007; HR: 0.09; CI: 0.02–0.53). On subanalysis of treatment-naïve patients, the median OS and PFS were 7.4 months and 2.8 months, respectively. The 3-, 6- and 12-month PFS rates were 43.5%, 38.6% and 24.8%, respectively. Pleural effusion was the only independent poor prognostic feature (p = 0.036; HR: 206.34; CI: 1.41–30,167.58).ConclusionIndependent prognostic features for survival outcomes include the presence of ascites, pleural effusions, hepatic vein tumor thrombus, and HCC with low attenuation (<40 HU) on unenhanced CT images. Although several biochemical variables were significant on univariate analysis, none were independent predictors of OS or PFS.

Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study

BackgroundTalazoparib, a poly(ADP-ribose) polymerase enzyme inhibitor, is approved for the treatment of patients with germline BRCA1/2 (gBRCA1/2)-mutated HER2-negative advanced breast cancer. This two-part study, a recently published dose-escalation part followed by the dose-expansion part reported here, evaluated the efficacy and safety of talazoparib in Japanese patients with gBRCA1/2-mutated advanced breast cancer.MethodsIn this open-label, multicenter phase 1 study (NCT03343054), the primary endpoint of the dose-expansion part was confirmed objective response rate (ORR), determined by investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Patients received the recommended phase 2 dose (1 mg/day; 0.75 mg/day moderate renal impairment).ResultsNineteen Japanese patients with gBRCA1/2-mutated locally advanced or metastatic breast cancer were enrolled. Confirmed ORR was 57.9% (11/19; 90% confidence interval [CI] 36.8–77.0). Stable disease was observed in 36.8% (7/19) of patients. Per investigator assessment, median PFS was 7.2 months (95% CI 4.1–not estimable) and 12-month OS rate was 84.7% (90% CI 57.5–95.1). Median OS was not reached; 17/19 patients were alive and censored at 12 months. All patients experienced treatment-related adverse events (AEs); the majority were hematologic. The most common treatment-related AE was anemia (68.4%; [13/19]). Grade 3/4 treatment-related AEs were observed in 52.6% (10/19) of patients. During the safety period, there were no grade 5 treatment-emergent AEs, treatment-related serious AEs, or deaths.ConclusionsIn Japanese patients with gBRCA mutations and locally advanced or metastatic breast cancer, talazoparib monotherapy was generally well tolerated and resulted in clinically meaningful ORRs.Clinicaltrials.gov identifierNCT03343054.