Safety Of Maintenance Therapy Research Articles

Efficacy and safety of maintenance therapy with anlotinib for advanced cholangiocarcinoma after first-line chemotherapy and the variations in efficacy based on different neutrophil-to-lymphocyte ratio (NLR)

ObjectiveThis study aimed to evaluate the clinical efficacy and safety of anlotinib as maintenance therapy in patients with advanced cholangiocarcinoma following first-line chemotherapy.MethodsThis retrospective study enrolled 154 patients with advanced biliary tract cancer admitted to the hospital between January 2020 and December 2022. All patients received first-line intravenous chemotherapy with gemcitabine combined with cisplatin, oxaliplatin, or tegafur. Among the 106 patients who achieved disease control, 47 received oral anlotinib hydrochloride (12 mg daily, 2 weeks on/1 week off) as maintenance therapy. Clinical efficacy, including ORR, DCR, DOR, PFS, and OS, was compared between the anlotinib maintenance and non-maintenance groups. Subgroup analysis based on NLR levels was also performed.ResultsAmong the 47 anlotinib maintenance patients, the ORR was 21.28% and the DCR was 51.06%. The median DOR was 36 weeks, and the median PFS was 43 weeks in the anlotinib group, versus 28 weeks and 38 weeks in the non-maintenance group, respectively. The median OS was not reached in the anlotinib group but was 48 weeks in the non-maintenance group. Patients receiving anlotinib maintenance had significantly longer DOR, PFS, and OS (all p < 0.05). Patients with low NLR levels had better survival benefits from anlotinib.ConclusionMaintenance therapy with anlotinib demonstrates potential efficacy and a reliable safety profile in patients with advanced cholangiocarcinoma following first-line treatment. The efficacy of anlotinib therapy appears to be influenced by NLR levels. Further validation with larger sample sizes is warranted to strengthen the robustness and reliability of the results.

Maintenance therapy with anlotinib after induction therapy with platinum-based chemotherapy for advanced non-small-cell lung cancer: A pooled analysis of 2 single-arm trials.

Maintenance therapy could significantly improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. Anlotinib is effective, tolerable, and convenient in administration as a third-line treatment for NSCLC. This study aimed to evaluate the efficacy and safety of maintenance therapy with anlotinib after platinum-based induction chemotherapy for patients with advanced NSCLC. This pooled analysis of 2 multicenter, open-label, single-arm, phase 2 clinical trials (ALTER-L014 and ALTER-L011) enrolled patients with locally advanced or metastatic NSCLC and without known sensitive mutations in China between September 2018 and January 2021. The primary outcome was progression-free survival. The secondary outcomes were objective response rate, disease control rate, overall survival, and safety. The data of 23 patients were pooled, with 15 from ALTER-L014 and 8 from ALTER-L011. At the cutoff date of June 13, 2021, the median progression-free survival since the start of maintenance therapy was 5.95 (95% confidence interval, 4.30-8.80) months. Nineteen patients had stable disease, 1 had a partial response and 3 had progressive disease. The objective response rate was 4.35%, while disease control rate was 86.96%. The median overall survival of the patients since the start of maintenance therapy was 18.60 (95% confidence interval, 6.87-22.80) months. The incidence of adverse events of grade ≥ 3 was 21.7%. Anlotinib might offer a new option for maintenance treatment in patients with locally advanced or metastatic NSCLC without known sensitive mutations after standard first-line platinum-based chemotherapy.

Efficacy and Safety of Maintenance Therapy Using Cetuximab in Patients with Metastatic Colorectal Cancer: Retrospective Study.

Cetuximab (CET) combined with chemotherapy significantly improved the survival in RAS and RAF wild-type metastatic colorectal cancer (mCRC) patients, while clinical evidence was lacking on the use of maintenance therapy (MT). The study aimed to explore the role of maintenance therapy following Cetuximab + chemotherapy and the optimal Cetuximab-based maintenance therapy regimen. We retrospectively reviewed data on the efficacy and safety of CET-based MT in patients with mCRC who achieved diseasecontrolafter induction therapy. Eighty-one patients with mCRC who achieved disease control after CET + chemotherapy induction were enrolled. Overall median progression-free survival (PFS) was 10.5 (95% CI = 8.8-12.2) months and median maintenance/observation PFS (mnPFS) was 6.0 (95% CI = 5.0-7.0) months. Among these 81 patients, 61 patients were prescribed MT (CET alone for 21 patients and CET + chemotherapy for 40 patients). Median PFS and mnPFS in the MT group were significantly longer than those for the non-MT group. Different MT regimens did not affect PFS and mnPFS significantly. Univariate and multivariate analysis demonstrated MT, complete response/partial response during induction therapy, and absence of peritoneal metastasis to be positively associated with longer PFS and mnPFS. Treatment-related adverse events (AEs) were tolerable during MT, and AE-related deaths were not observed. MT with CET or CET + chemotherapy was an appropriate option following initial induction chemotherapy for patients with RAS and RAF wild-type mCRC. This strategy endowed survival benefits and a tolerable safety profile.

P566 Maintenance vedolizumab treatment in pediatric IBD: 54-week follow-up of the prospective multicenter VEDOKIDS study

Abstract Background Prospective long-term data on vedolizumab (VDZ) in children with Crohn’s disease (CD) and ulcerative colitis (UC) are lacking. In this prospective, multicenter cohort study, we aimed to evaluate the effectiveness and safety of maintenance therapy with VDZ in pediatric CD and UC. Methods Children commenced on VDZ were followed at baseline and 2, 6, 14, 30 and 54 weeks thereafter. Serum for drug levels and stool for calprotectin were repeatedly obtained. The primary outcome was sustained steroid-free remission (SSFR), defined as clinical remission )PUCAI&amp;lt;10 or wPCDAI&amp;lt;12.5) without steroids/EEN at both 30 and 54 weeks, analyzed under the ITT principle. Results 139 children were enrolled (77 [55%] UC, 62 [45%] CD; age 14.9 years (IQR 12.0-16.6). Of the 119 (86%) children &amp;gt;30kg, 110 (92%) received a dose of 300mg; 20 (14%) weighed&amp;lt;30 kg and received a dose of 8.3mg/kg (IQR 7–10.3). Week-54 remission rate was 52% in UC and 37% in CD; SSFR rates were 42% and 24%, respectively (OR 2.2 [95%CI 1.1-4.7] Figure). SSFR rate was numerically higher in isolated colonic CD than in ileal disease (5/11 [45%] vs 10/49 [20%], OR 3.3 [95%CI 0.8-12.9]; p=0.08). Infusion interval was shortened in 22 children (10 [13%] UC, 12 [19%] CD), of whom none achieved SSFR. SSFR rate was higher in week-6 responders compared to non-responders in UC (51% vs 27%, OR 2.9 [1.1-7.7]) and CD (35% vs 14%, OR 3.4 [95%CI 0.95-12.4]), similar to the week-14 figures (UC: 50% vs 22%, OR 3.6 [1.2-11.1]; CD: 36% vs 8%, OR 6.2 [1.3-30.8]). SSFR was eventually achieved in 49% of UC children having mild disease at week-6 and 14% with moderate-severe disease (OR 5.8 [95%CI 1.2-28.2]); the corresponding rates in CD were 31% and 0% (p=0.02). In multivariable models, the best predictors in CD were lower wPCDAI at baseline (AUROC 0.88 [95%CI 0.79-0.96]; optimal cutoff 25 (sens/spec 76%/80%)) and at week 6 (0.90 [0.82-0.98]; optimal cutoff 17.5 (80%/87%)). In UC, the best predictors were PUCAI at week 6 (0.70 [0.57-0.82]; optimal cutoff 10 (64%/57%)) and at week-14 (0.78 [0.67-0.89]; optimal cutoff 5 (76%/60%; Table). In children &amp;lt;30kg, SSFR was associated with week 6 drug levels &amp;gt;30ug/mL, not reaching statistical significance (3/6 [50%] vs 1/8 [13%], OR 7.0 [95%CI 0.5-97]). By week 54, 197 adverse events were recorded, of which were VDZ-related in 8 (5.8%) children, and in 2 (1.4%) led to stopping VDZ; none were severe. There was 1 lymphoma case judged to be unrelated to VDZ. Conclusion VDZ was effective for maintaining remission, more so in UC and in colonic CD. The likelihood of eventually achieving SSFR was very low in children with moderate-severe disease or those not showing response at week-6, particularly in CD.

Maintenance therapy for chronic lymphocytic leukaemia.

Maintenance therapy for chronic lymphocytic leukaemia.

Maintenance Therapy With Cetuximab After FOLFIRI Plus Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer

The optimal maintenance strategy after induction chemotherapy with anti-epidermal growth factor receptor antibody for patients with RAS wild-type metastatic colorectal cancer (mCRC) remains to be debated. To evaluate the efficacy and safety of maintenance therapy with single-agent cetuximab after FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) plus cetuximab induction therapy. The TIME (Treatment After Irinotecan-Based Frontline Therapy: Maintenance With Erbitux]) (PRODIGE 28 [Partenariat de Recherche en Oncologie Digestive]-UCGI 27 [UniCancer GastroIntestinal Group]) phase 2 noncomparative, multicenter randomized clinical trial was conducted from January 15, 2014, to November 23, 2018, among 139 patients with unresectable RAS wild-type mCRC. The cutoff date for analysis was July 21, 2022. After first-line induction therapy with 8 cycles of FOLFIRI plus cetuximab, patients without disease progression were randomized (1:1) to biweekly maintenance with cetuximab or observation. On disease progression, the same induction regimen was recommended for 16 weeks followed by further maintenance with cetuximab or observation until disease progression under the full induction regimen. The primary end point was the 6-month progression-free rate from randomization. Analysis was performed on an intention-to-treat basis. An exploratory biomolecular analysis, using next-generation sequencing, investigated the putative prognostic value of the tumor mutation profile. Of 214 patients enrolled (141 men [65.9%]; median age, 67 years [range, 23-85 years]), 139 were randomized to receive cetuximab (n = 67; 45 men [67.2%]; median age, 64 years [range, 34-85 years]) or to be observed (n = 72; 50 men [69.4%]; median age, 68 years [23-85 years]). The 6-month progression-free rate was 38.8% ([26 of 67] 95% CI, 27.1%-51.5%) in the cetuximab group and 5.6% ([4 of 72] 95% CI, 1.5%-13.6%) in the observation group. At a median follow-up of 40.5 months (95% CI, 33.6-47.5 months), median progression-free survival (PFS) from randomization was 5.3 months (95% CI, 3.7-7.4 months) in the cetuximab group and 2.0 months (95% CI, 1.8-2.7 months) in the observation group. Median overall survival (OS) was 24.8 months (95% CI, 18.7-30.4 months) in the cetuximab group and 19.7 months (95% CI, 13.3-24.4 months) in the observation group. In an exploratory multivariate analysis, any tumor-activating mutation in the mitogen-activated protein kinase (MAPK) pathway genes was associated with shorter PFS from randomization regardless of treatment group (hazard ratio, 1.63 [95% CI, 1.01-2.62]; P = .04). The most frequent grade 3 or 4 treatment-related toxic effect in the cetuximab group during maintenance therapy was rash (8 of 67 [11.9%]). The randomized clinical trial did not meet its primary end point but suggests clinically meaningful PFS and OS benefits associated with cetuximab maintenance therapy. However, maintenance cetuximab or treatment breaks after first-line combination FOLFIRI-cetuximab therapy seems inappropriate for patients with MAPK-mutated independently of the side of primary tumor. A more complete assessment of MAPK pathway mutations warrants further investigation to the refine treatment strategy for patients with RAS wild-type mCRC. ClinicalTrials.gov Identifier: NCT02404935.

Efficacy and safety of maintenance therapy using bevacizumab for advanced ovarian cancer

Efficacy and safety of maintenance therapy using bevacizumab for advanced ovarian cancer

Impact of maintenance therapy using a half dose of the bacillus Calmette\u2013Gu\xe9rin Tokyo strain on recurrence of intermediate and high-risk nonmuscle invasive bladder cancer: a retrospective single-center study

BackgroundData are scarce regarding intravesical maintenance therapy (MT) with the low-dose bacillus Calmette–Guérin (BCG) Tokyo strain. We investigated the efficacy and safety of MT with a half dose of the Tokyo strain for patients following transurethral resection of nonmuscle invasive bladder cancer (NMIBC).MethodsThis study retrospectively reviewed clinical data on 78 patients diagnosed with intermediate or high-risk NMIBC followed by either MT (n = 38) or IT alone (n = 40) between January 2012 and March 2018. Statistical analysis was performed to compare recurrence-free survival (RFS) and adverse effects between the two groups. BCG was instilled once weekly for 6 weeks as IT, then once weekly in 2-week for a total of 20 instillations over 3 years.ResultsKaplan–Meier analyses showed that patients undergoing MT had significantly better RFS than did those undergoing IT alone (hazard ratio (HR):0.32, 95% confidence interval (CI):0.12–0.89, P = 0.02). The 3-year RFS was 65.0% in the IT group and 89.5% in the MT group. Multivariate analysis showed that MT was associated with a reduced risk of recurrence (HR: 0.32, 95% CI:0.11–0.93, P = 0.03). One MT patient (2.6%) exhibited progression.ConclusionsThe BCG Tokyo strain showed acceptable efficacy and safety in patients undergoing MT; thus, it is a potential treatment for preventing bladder cancer recurrence.

A randomized phase 3 study of maintenance therapy with S‐1 plus best supportive care versus best supportive care after induction therapy with carboplatin plus S‐1 for advanced or relapsed squamous cell carcinoma of the lung (WJOG7512L)

A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S-1 after induction therapy with carboplatin plus S-1 in patients with advanced squamous non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3weeks) plus S-1 (40mg/m2 twice per day on days 1-14 every 3weeks) as induction therapy. Patients who did not progress after 4 cycles of induction therapy were randomized to receive either S-1 plus best supportive care (BSC) or BSC alone. The primary objective of the study was to confirm the superiority of S-1 plus BSC in comparison with BSC alone with respect to progression-free survival. Of the 365 patients enrolled in the study, 347 participated in the induction phase, and 131 of these individuals were randomized to receive S-1 plus BSC (n=67) or BSC alone (n=64). The risk of disease progression was significantly lower for patients in the S-1 plus BSC arm than those in the BSC-alone arm (hazard ratio, 0.548; 95% confidence interval, 0.374-0.802; P=.0019). The most common toxicities during maintenance therapy with S-1 included anorexia, anemia, and fatigue, but most cases were not severe. Continued maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC previously treated with carboplatin plus S-1.

Treating progressive disseminated histoplasmosis in people living with HIV.

BackgroundProgressive disseminated histoplasmosis (PDH) is a serious fungal infection that affects people living with HIV. The best way to treat the condition is unclear.ObjectivesWe assessed evidence in three areas of equipoise.1. Induction. To compare efficacy and safety of initial therapy with liposomal amphotericin B versus initial therapy with alternative antifungals.2. Maintenance. To compare efficacy and safety of maintenance therapy with 12 months of oral antifungal treatment with shorter durations of maintenance therapy.3. Antiretroviral therapy (ART). To compare the outcomes of early initiation versus delayed initiation of ART.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane CENTRAL; MEDLINE (PubMed); Embase (Ovid); Science Citation Index Expanded, Conference Proceedings Citation Index‐Science, and BIOSIS Previews (all three in the Web of Science); the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry, all up to 20 March 2020.Selection criteriaWe evaluated studies assessing the use of liposomal amphotericin B and alternative antifungals for induction therapy; studies assessing the duration of antifungals for maintenance therapy; and studies assessing the timing of ART. We included randomized controlled trials (RCT), single‐arm trials, prospective cohort studies, and single‐arm cohort studies.Data collection and analysisTwo review authors assessed eligibility and risk of bias, extracted data, and assessed certainty of evidence. We used the Cochrane 'Risk of bias' tool to assess risk of bias in randomized studies, and ROBINS‐I tool to assess risk of bias in non‐randomized studies. We summarized dichotomous outcomes using risk ratios (RRs), with 95% confidence intervals (CI).Main resultsWe identified 17 individual studies. We judged eight studies to be at critical risk of bias, and removed these from the analysis.1. InductionWe found one RCT which compared liposomal amphotericin B to deoxycholate amphotericin B. Compared to deoxycholate amphotericin B, liposomal amphotericin B may have higher clinical success rates (RR 1.46, 95% CI 1.01 to 2.11; 1 study, 80 participants; low‐certainty evidence). Compared to deoxycholate amphotericin B, liposomal amphotericin B has lower rates of nephrotoxicity (RR 0.25, 95% CI 0.09 to 0.67; 1 study, 77 participants; high‐certainty evidence). We found very low‐certainty evidence to inform comparisons between amphotericin B formulations and azoles for induction therapy.2. MaintenanceWe found no eligible study that compared less than 12 months of oral antifungal treatment to 12 months or greater for maintenance therapy.For both induction and maintenance, fluconazole performed poorly in comparison to other azoles.3. ARTWe found one study, in which one out of seven participants in the 'early' arm and none of the three participants in the 'late' arm died.Authors' conclusionsLiposomal amphotericin B appears to be a better choice compared to deoxycholate amphotericin B for treating PDH in people with HIV; and fluconazole performed poorly compared to other azoles. Other treatment choices for induction, maintenance, and when to start ART have no evidence, or very low certainty evidence. PDH needs prospective comparative trials to help inform clinical decisions.

Comparison of PARPis with Angiogenesis Inhibitors and Chemotherapy for Maintenance in Ovarian Cancer: A Network Meta-Analysis.

Seventy-five percent of ovarian cancer would relapse within 18-28months after platinum-base chemotherapy. Evidence suggests that maintenance chemotherapy is effective in prolonging remission. Recent target therapies such as poly(ADP-ribose) polymerase inhibitors (PARPis) and angiogenesis inhibitors (AIs) are known to ease burden and recurrence of ovarian cancer. There is limited data for head-to-head comparison of PARPis, AIs, and chemotherapeutic agents (CTAs) as maintenance treatment. This network meta-analysis thus assessed the effectiveness and toxicity of these three maintenance therapies in patients with ovarian cancer. We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials assessing efficacy and safety of maintenance therapy in patients with ovarian cancer. Primary outcome was progression-free survival (PFS) as assessed by blinded review; safety and tolerability were secondary outcomes. A network meta-analysis to compare three drug classes was performed using statistical software R. We included 24 trials (11,366 patients) assessing efficacy and safety of PARPis (n = 4), AIs (n = 12), and CTAs (n = 8). PARPis [hazard ratio (HR) 0.64; 95% credible intervals (CrI) 0.55-0.73] and AIs (HR 0.87; 95% CrI 0.81-0.93) showed significant improvement in PFS compared to placebo but not CTA (HR 1.00; 95% CrI 0.86-1.15). PARPis showed significant improvement in PFS compared to AIs (HR 0.73; 95% CrI 0.63-0.86) and CTA (HR 0.64; 95% CrI 0.52-0.78). Adverse events (AEs) leading to treatment discontinuation and dose reduction were lower in PARPis [incidence rate ratio (IRR) 0.60; CrI 0.31-1.18 and IRR 0.73, 95% CrI 0.50-1.06, respectively] compared to AIs, but the differences were not significant. PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of implications caused by AEs when compared to AIs. This network meta-analysis provides valuable evidence and significant insights into treatment of ovarian cancer.

PB2330 EFFICACY OF MAINTENANCE THERAPY AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN HIGH‐RISK AGGRESSIVE LYMPHOMA: A SINGLE‐CENTER NON‐RANDOMIZED STUDY

Background:Autologous hematopoietic stem cell transplantation is the main treatment for lymphoma. While relapse after autologous hematopoietic stem cell transplantation (ASCT) is still challenging for high‐risk aggressive lymphoma.Aims:This study was to investigate the efficacy and safety of maintenance therapy post‐ASCT.Methods:From June 2009 to December 2018, patients with high‐risk aggressive lymphoma in our hospital were treated with maintenance therapy post‐ASCT according to the patient's needs and wishes, and then assigned to maintenance group or observation group. The end point of follow‐up was disease progression or death. The 4‐year overall survival (OS) and disease‐free survival (DFS) were compared between these two groups.Results:A total of 92 patients were enrolled, apart from 2 cases of early death, the remaining 90 patients underwent ASCTsuccessfully and achieved CR post‐ASCT. 59 patients were assigned to the observation group, and 31 patients to the maintenance group, including 22 with rituximab regimen,7 with DPP/DCEP‐G alternation regimen, and 2 with Chidamideregimen. There were no significant differences in gender, age,diagnosis,IPI score,pre‐transplant disease status, and hematopoietic reconstitution between the two groups. The main causes of death were disease recurrence. No serious adverse reactions occurred during the maintenance treatment period. After a median follow‐up of 616 days (12‐2854 days), and the DFS of the 1st, 2nd,3rd and 4thyears were67.1% VS 95.2%, 51.1% VS 90.5%, 48.1% VS 90.5%, 43.8% VS 90.5% (P = 0.002), respectively. The OS of the 1st, 2nd, 3rd and 4thyears were 90.0% VS 100%, 84.4% VS 95.2%, 77.3% VS 95.2%, 73.3% VS 95.2% (P = 0.126), respectively.For the overall survival rate, single factor analysis showed age &lt;30 years old, LDH increased before ASCTwere prognostic factors affecting OS; COX multi‐factor regression analysis showed age &lt;30 years old, LDH increased before ASCTwere independent prognostic factors for OS. The risk of death in patients &lt;30 years of age was 4.376 times higher than that in patients aged 30 years or older (P = 0.026, HR = 4.376, 95% CI = 1.188‐16.116). The risk of death in patients with LDH increased before ASCT was 5.165 times higher than in patients with normal LDH before ASCT (P = 0.015, HR = 5.165, 95% CI = 1.375‐19.395).For the disease‐free survival rate, single factor analysis showed that the initial admission to LDH increased, LDH increased before ASCT, IPI score≥2 points, maintenance treatment after ASCT were prognostic factors for DFS; COX multi‐factorregression Analysis showed that LDH increased before ASCTand maintenance treatment after ASCT were independent prognostic factors for DFS. The risk of recurrence of patients with LDH increased before ASCT was 2.648 times higher than that of normal LDH patients before ASCT (P = 0.034, HR = 2.648, 95% CI = 1.078‐6.507), and the risk of recurrence in maintenance‐treated patients after ASCT was 0.130 times than that in patients without maintenance therapy after ASCT (P = 0.006, HR = 0.130, 95% CI = 0.031‐0.557).Conclusion: Maintenance therapy post‐ASCT could reduce the risk of relapse and promote disease‐free survival, which deserves further investigation.Summary/Conclusion:Maintenance therapy post‐ASCT could reduce the risk of relapse and promote disease‐free survival, which deserves further investigation.image

The role of maintenance therapy in patients with diffuse large B cell lymphoma: A systematic review and meta-analysis.

Randomized trials of maintenance therapy (MT) in diffuse large B cell lymphoma (DLBCL) are inconclusive regarding its effect on overall survival (OS) and disease control. We aimed to examine the efficacy and safety of MT in this meta-analysis. Systematic review and meta-analysis of randomized controlled trials comparing MT with observation or placebo, in patients with DLBCL, who achieved complete response (CR) or partial response (PR) after first-line chemotherapy with or without rituximab. Primary outcome was OS. Secondary outcomes included relapse rate, disease control (defined as progression-free survival, event-free survival, or disease-free survival, as reported in the original trials), and safety. Our search yielded 14 trials including 5122 patients. Median age of patients was 49 to 70years. Six trials included rituximab as the MT; three included Interferon alfa; other trials include thalidomide, lenalidomide, cyclophosphamide and prednisone, serine threonine kinase inhibitor enzastaurin, and mTOR inhibitor everolimus. MT did not improve OS compared to observation, OR 0.91, (95% CI 0.78-1.07). Results were the same in a subgroup analysis by the type of maintenance (rituximab vs other). MT did decreased relapse rate, RR 0.76 (95% CI 0.65-0.89) and improved disease control, OR 0.74 (95% CI 0.65-0.84). Disease control was significantly improved in the subgroup of studies evaluating rituximab as maintenance OR 0.61 (95% CI 0.47-0.79) and in the subgroup of R-CHOP induction studies OR 0.77 (95% CI 0.67-0.88). Serious or grade III/IV adverse events including neutropenia and infections were significantly more common in the maintenance arm, RR=1.69 (95% CI 1.29-2.22). MT in patients with DLBCL achieving CR or PR after induction therapy did not affect OS, yet it decreased relapse rate and improved disease control at the cost of higher infection rate. Our data do not support routine administration of MT in patients with DLBCL.

A Randomized Phase II Study of Axitinib as Maintenance Therapy After First-line Treatment for Metastatic Colorectal Cancer

IntroductionThe aim of this study was to evaluate the efficacy and safety of maintenance therapy with axitinib versus placebo following induction therapy in patients with metastatic colorectal cancer (mCRC). Patients and MethodsIn this double-blinded, phase II trial, patients with mCRC who had not progressed after 6 to 8 months of first-line chemotherapy were randomized to receive axitinib (5 mg twice a day) (arm A) or placebo (arm B). ResultsForty-nine patients were included: 25 in arm A and 24 in arm B. The median follow-up was 26.07 months (95% confidence interval [CI], 18.44-31.73 months). Progression-free survival (PFS) rate at 6 months was 40.00% (95% CI, 21.28%-58.12%) in the axitinib arm versus 8.33% (95% CI, 1.44%-23.30%) in the placebo arm (P = .0141). The median PFS was statistically significantly longer in the axitinib group than in the placebo group (4.96 vs. 3.16 months; hazard ratio, 0.46; 95% CI, 0.25-0.86; P = .0116). Median overall survival was also longer in the axitinib arm but did not reach statistical significance (27.61 vs. 19.99 months; hazard ratio, 0.68; 95% CI, 0.31-1.48; P = .3279). Grade 3 to 4 treatment-related toxicities were experienced by 7 patients (28%) in cohort A and 1 patient (4%) in cohort B (P = .0488). The most frequent grade 3 to 4 treatment-related toxicities were hypertension, diarrhea, and asthenia. There were no toxic deaths. The study was prematurely closed because of slow recruitment. ConclusionsIn our study, maintenance treatment with axitinib monotherapy showed a significant increase in PFS and a good safety profile. Axitinib should be further explored as a possible option for first-line chemotherapy maintenance treatment in patients with mCRC.

Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis.

Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM.

A prospective study of the efficacy and safety of maintenance therapy with recombinant human thrombopoietin in patients with primary immune thrombocytopenia: a multicenter study

目的评价重组人血小板生成素（rhTPO）减量维持治疗对于原发免疫性血小板减少症（ITP）的有效性和安全性。方法ITP患者接受连续2周的rhTPO治疗（300 U·kg−1·d−1），PLT ≥ 50×109/L者进入维持治疗。入组者初始给予隔日用药方案，根据血小板计数调整rhTPO给药间隔，维持PLT（30~100）×109/L，维持治疗共12周。结果在91例rhTPO治疗有效的患者中，14例退出研究（12例依从性欠佳，2例经研究者决定换用其他治疗方案）。77例患者完成研究，其中38例在12周维持治疗中始终维持治疗有效（PLT≥30×109/L）。在维持治疗第4、8、12周时，治疗有效率分别为92.6%（63/68）、82.7%（43/52）、85.0%（34/40）。所有接受治疗患者的中位血小板计数波动于（70~124）×109/L。rhTPO相关不良反应发生率为7.7%，均为轻度。结论延长给药间隔的减低剂量rhTPO维持治疗可使绝大多数ITP患者的血小板计数维持于安全水平，但给药间隔差异较大，需进行个体化调整。

Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety

The optimal strategy of maintenance therapy for patients with mCRC is controversial. This study was to evaluate the efficacy and safety of maintenance therapy with capecitabine versus observation following inductive chemotherapy in patients with metastatic colorectal cancer. In this randomized, open-label, multicenter, phase III trial, patients who received 18-24 weeks of induction chemotherapy with XELOX or FOLFOX and achieved disease control were randomly assigned centrally (1:1) to receive maintenance therapy of capecitabine or only observation until disease progression. The primary end point was progression-free survival (PFS) from randomization; the secondary end points included overall survival (OS), PFS from induction treatment (PFS2) and safety. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02027363. Between 30 July 2010 and 15 September 2013, 274 patients were enrolled in the study from 11 sites in China and randomly assigned to maintenance group (n = 136) or observation group (n = 138). Clinicopathological characteristics were balanced in two groups. The median follow-up time from randomization was 29.0 months [interquartile range (IQR) 21-36 months]. The primary end point of PFS was statistically significantly longer in capecitabine maintenance group than in observation group {6.43 [95% confidence interval (CI) 5.26-7.71] versus 3.43 (2.83-4.16) months, HR 0.54 (0.42-0.70), P < 0.001}. The median OS of capecitabine maintenance group was longer than that of observation group, but not statistically significant [25.63 (22.46-27.80) versus 23.30 (19.68-26.92) months; HR 0.85 (0.64-1.11), P = 0.2247]. Similar safety profiles were observed in both arms. The most common grade 3 or 4 toxicities in capecitabine maintenance group versus observation group were neutropenia, hand-foot syndrome, and mucositis. Maintenance therapy with a single agent of capecitabine can be considered an appropriate option following the induction of XELOX or FOLFOX in mCRC patients with acceptable toxicities. NCT02027363.

Double-blind, placebo-controlled, randomized, phase 2 study to evaluate the efficacy and safety of maintenance therapy with anti-TA-MUC1 monoclonal antibody PankoMab after chemotherapy in patients with recurrent epithelial ovarian carcinoma.

TPS5622 Background: PankoMab is a potent humanized glyco-engineered IgG1 recognizing the tumor-specific carbohydrate/protein epitope TA-MUC1 expressed virtually only on tumor cells of a wide variet...

A Randomized Comparison Of Maintenance Therapy With Subcutaneous Rituximab For 2 Years Versus Until Progression In Patients With Indolent Non-Hodgkin's Lymphoma: Interim Safety Data From The Mabcute Study

BackgroundRituximab is part of the standard induction and maintenance therapy for most patients with first-line or relapsing indolent non-Hodgkin's lymphoma (iNHL). However, the optimal duration of maintenance is still to be defined. The MABCUTE trial is designed to evaluate the efficacy and safety of maintenance therapy with subcutaneous (SC) rituximab until disease progression (PD). Patients with relapsed or refractory iNHL, who respond to induction and an initial 2 years' maintenance therapy, are randomized to receive additional maintenance therapy or observation. Here we report the findings of a planned interim safety analysis in the first 231 patients enrolled in the trial. MethodsMABCUTE (NCT01461928) is an ongoing multicenter, randomized, parallel-group, phase IIIb study that started in December 2011. Eligible patients were aged ≥18 years with relapsed or refractory CD20+ iNHL (histologically confirmed) following ≥1 line of immunotherapy and/or chemotherapy and/or radiotherapy. Patients were scheduled to receive induction therapy consisting of rituximab every 3–4 weeks for 8 cycles (intravenous [IV] 375 mg/m2 in cycle 1 then SC 1400 mg in cycles 2–8) and 6–8 cycles of standard chemotherapy. Patients who achieved a complete or partial response (CR/PR) continued into standard maintenance (rituximab SC 1400 mg every 8 weeks for 24 months). Upon completion of standard maintenance, patients in sustained CR/PR will be randomized to receive additional maintenance (rituximab SC 1400 mg every 8 weeks) until PD, or observation. ResultsAt data cut-off (January 16, 2013), the safety population consisted of 216 patients who had received ≥1 dose of rituximab SC: 70 (32%) had completed induction therapy, 122 (57%) were receiving induction therapy, and 24 (11%) had discontinued induction therapy. A total of 58 (27%) patients had continued into standard maintenance, with 2 patients having subsequently discontinued maintenance therapy. Patients had a median age of 64.5 years (range, 20–90). At screening, the most common types of iNHL were follicular NHL (n=131, 61%), marginal zone lymphoma (n=41, 19%), and Waldenström's macroglobulinemia (n=31, 14%). The most commonly used chemotherapy regimens were bendamustine (n=137, 63%), CHOP (n=31, 14%) and CVP (n=21, 9.7%). During therapy, AEs occurred in 174 (81%) patients (Table), grade 3 or higher AEs in 70 (32%) patients and serious AEs (SAEs) in 44 (20%) patients. Administration-related reactions (ARRs) were reported by 61 (28%) patients after 1 dose of rituximab IV and by 89 (41%) patients after a median (range) of 5 (1–11) doses of rituximab SC. The majority of ARRs were mild to moderate and transient, and expected with the change in the route of administration. Overall, 25 patients had grade 4 hematological events, most commonly neutropenia (22 patients). Only 4 cases of neutropenia lasted >14 days and these resolved without interruption to treatment. One patient had a grade 4 non-hematological event (thrombosis and pulmonary embolism that resolved after 12 days). Among the 26 patients who discontinued study treatment, reasons given were AEs (n=8; skin reactions [3], neutropenia [2], general health problems [2], and oseophagitis [1]), patient or investigator request (n=6), PD (n=5), death (n=2), and other (n=5). One patient died of bronchopneumonia and sepsis due to leucopenia and 1 died of myocarditis; neither was considered by the investigator to be related to the study drug.Table. Summary of AEsAdverse eventNumber of patients (%)SAE44 (20)Grade 3 or higher AE70 (32)Any grade AE occurring in ≥10% of patients174 (81)Neutropenia44 (20)Pyrexia35 (16)Asthenia24 (11)Nausea41 (19)Constipation23 (11)Diarrhea22 (10) ConclusionsRituximab SC is associated with ARRs that are transient and mainly mild to moderate in severity. The incidence and intensity of other hematological and non-hematological toxicities are within the expected range for rituximab SC or IV administration. No new safety signals or concerns associated with rituximab SC were identified during induction and maintenance therapy in this interim safety analysis, as confirmed by the Independent Data Monitoring Committee. Rituximab SC appears to be well tolerated and the study continues. Disclosures:Rule:Pharmacyclics, Inc: Consultancy; J&J: Consultancy; F. Hoffmann-La Roche: Consultancy. Off Label Use: Rituximab, administered as an IV infusion, is approved for use in a number of hematologic indications. The data presented here assess a subcutaneous approach to rituximab administration in patients with indolent Non-Hodgkin's Lymphoma. Briones:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartris: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Honoraria. Casasnovas:F. Hoffmann-La Roche: Consultancy, Research Funding. Pocock:F. Hoffmann-La Roche: Honoraria. Osborne:F. Hoffmann-La Roche: Employment. Smith:F. Hoffmann-La Roche: Employment. Zaja:F. Hoffmann-La Roche: Consultancy.

A randomized phase II trial of maintenance therapy with Sorafenib in front-line ovarian carcinoma

ObjectivesSorafenib, an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway, has shown potential activity in patients with recurrent ovarian cancer (OC). One strategy to prolong disease control and survival in patients with OC is maintenance therapy after achieving a complete response. A double-blind, randomized, placebo-controlled, phase II study to assess the efficacy and safety of maintenance therapy with sorafenib in the treatment of OC is presented. MethodsPatients with epithelial OC or primary peritoneal cancer in complete remission were randomized to sorafenib 400mg BID or matching placebo. The primary endpoint was progression-free survival (PFS). ResultsOf 246 randomized patients, 93% had OC; baseline characteristics were balanced between treatment arms. There was no significant difference between sorafenib and placebo arms for PFS (median 12.7 vs 15.7months; hazard ratio 1.09; 95% CI 0.72–1.63), although there was a notable imbalance in early censoring. The most common ≥grade 3 adverse events (AEs) were hand–foot skin reaction (39.0% vs 0.8%) and rash (14.6% vs 0%). More patients receiving sorafenib versus placebo required dose reductions (67.5% vs 30.1%), resulting in a lower than planned median daily dose (median 584.6 vs 800.0mg). Treatment with sorafenib was of shorter duration (median 17.6 vs 51.9weeks) with more frequent discontinuations due to AEs (37.4% vs 6.5%). ConclusionsSorafenib 400mg BID cannot be recommended as maintenance therapy for patients with OC in complete remission. Assessment of efficacy was limited by the high rate of dose reductions and early discontinuations.