Determining the Benefits of Rituximab + Chemotherapy for Patients with Untreated Follicular Lymphoma: A Comprehensive Meta-Analysis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3330-3330 ◽  
Author(s):  
Josiah N. Orina ◽  
Christopher R. Flowers
Keyword(s):  
Follicular Lymphoma ◽  
Watchful Waiting ◽  
Meta Analysis ◽  
Single Agent ◽  
Inclusion Criteria ◽  
First Line ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
American Society ◽  
Meta Analyses

Abstract Background: Current guidelines offer numerous options for initiating therapy in patients with untreated, advanced stage follicular lymphoma (FL). Selecting among these options that include watchful waiting, single-agent and combination chemotherapy, monoclonal antibodies, and radioimmunotherapy, remains challenging. Recent data suggest that chemotherapy combined with a monoclonal antibody may alter patterns of relapse and overall survival for pts with FL (Fisher, Blood 2004). While rituximab (R) chemotherapy combinations have become commonly used for untreated pts with FL, to date, the optimal first-line therapy remains undefined. To address this issue, we updated a systematic literature review and performed a meta-analysis of first-line therapy for untreated FL that examined the effect of various chemotherapy regimens combined with R on response rates and survival in patients with untreated FL. Methods: The comprehensive systematic review included searches the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1996–6/2006), EMBASE (1/1980–7/2006), American Society of Hematology Annual Meeting abstracts (2002–2005), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2006). Each database was searched using combinations of the term follicular lymphoma and the terms for medications and treatment regimens. Inclusion criteria for studies were as follows: 1) Inclusion of patients with untreated stage III/IV FL grades 1, 2, or 3; 2) Intervention with chemotherapy and/or immunotherapy, radioimmunotherapy, or watchful waiting; 3) Reporting in English of the following treatment outcome measures specifically for patients with FL: CR/CR-unconfirmed, overall response rate (OR), and at least one form of survival data. Abstracts subsequently published as papers were excluded. Extracted data included pre-treatment disease status, treatment regimen, median follow-up time, progression free survival, overall survival, CR and OR. The following treatment strategies from peer-review publications were analyzed: single agent R, R-CVP, R-CHOP, and fludarabine-combinations with R (R-Fcom). In meta-analyses of selected studies, we utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing treatment regimens’ CR/CRu to the spontaneous CR in patients undergoing watchful waiting (4.6%; Ardeshna et al. Lancet, 2003). Results: In total, over 3135 abstracts were reviewed to identify 11 studies meeting the inclusion criteria for this analysis. These studies included data from 3144 patients. Only one study presenting CR data for R-CVP (36%, 95% confidence interval: 28%–44%) met inclusion criteria. The meta-analyses estimated the CR rate associated with single-agent R to be 30% (95% CI: 20%–40%), R-CHOP to be 62% (30%–94%), and R-Fcom to be 85% (76%–94%) (random effects; see Figure). Conclusions: R-CHOP and R-fludarabine combinations appear to produce the highest CR rates for untreated pts with FL. Meta-analysis can aid clinicians in therapeutic decision making as they weight the risks and benefits of various regimens for newly diagnosed pts. Figure Figure

Determining the Benefits of Chemotherapy for Achieving Complete Response in Patients with Untreated Advanced Stage Follicular Lymphoma: A Systematic Review and Meta-Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 290-290 ◽  
Author(s):  
Josiah N. Orina ◽  
Susan G. Moore ◽  
Mary Jo Lechowicz ◽  
Christopher R. Flowers
Keyword(s):  
Follicular Lymphoma ◽  
Watchful Waiting ◽  
Meta Analysis ◽  
Single Agent ◽  
Complete Response ◽  
Inclusion Criteria ◽  
First Line ◽  
Treatment Regimens ◽  
American Society ◽  
Meta Analyses

Abstract Background:Although advanced stage follicular lymphoma (FL) is considered incurable with standard therapy, and early institution of therapy has not demonstrated benefits over watchful waiting, novel strategies such as lymphoma vaccines and maintenance rituximab(R) provide opportunities for achieving prolonged disease-free intervals. Promoting the benefits of these strategies will depend upon improving the complete response rate(CR) with initial treatment. To date, the optimal first-line therapy remains undefined. To address this issue, we conducted a systematic literature review and meta-analyses comparing first-line chemotherapy regimens for FL. Methods:We searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1966–6/2005), EMBASE (1/1980–7/2005), American Society of Hematology Annual Meeting abstracts (2002–2004), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2005). Each search used combinations of the term follicular lymphoma and terms for medications and treatment regimens. Criteria for including studies were: Inclusion of patients with untreated stage III/IV FL; Intervention with chemotherapy and/or immunotherapy, radioimmunotherapy, or watchful waiting; Reporting in English of the following treatment outcome measures for patients with FL: CR/CR-unconfirmed, overall response rate (OR), and at least one form of survival data. Extracted data included pre-treatment disease status, treatment regimen, median follow-up time, progression free survival, overall survival, CR and OR. The following treatment strategies from peer-review publications were analyzed: single-agent fludarabine(F), fludarabine-combinations(F-com), single-agent alkylators(A), alkylator-combinations (without anthracycline), and anthracycline-combinations. In meta-analyses of selected studies, we utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing treatment regimens’ CR/CRu to the spontaneous CR in patients undergoing watchful waiting (4.6%; Ardeshna et al. Lancet, 2003). Results:Over 1800 abstracts were reviewed yielding 37 reported treatments that met inclusion criteria and included 2709 patients. The benefits of initial chemotherapy for achieving CR are shown in Figure 1. Single-agent F and A had similar benefits, as did F-com and CHOP. Substantial heterogeneity existed among other alkylator and anthracycline combinations limiting their ability to be combined using meta-analysis. Overall, chemotherapy provided a 49% improvement in the chances of attaining CR (95% CI:41%–57%). Meta-analyses of single agent R and RCHOP showed CR of 26% (95% CI:18%–34%) and 74% (95% CI:65%–83%) respectively (Figure 1B). Insufficient numbers of studies met inclusion criteria to examine the benefits of adding R to other regimens. Conclusions:CHOP and F-com provide the greatest likelihood of achieving CR in untreated FL. This benefit is even greater in CHOP patients who receive R. Selection of an initial regimen for patients with FL will depend on patient-specific factors and future plans for other therapies. Figure Figure

scholarly journals Lenalidomide in follicular lymphoma

Blood ◽  
2020 ◽  
Vol 135 (24) ◽  
pp. 2133-2136 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Nathan H. Fowler
Keyword(s):  
United States ◽  
Follicular Lymphoma ◽  
Single Agent ◽  
The United States ◽  
First Line ◽  
Safety And Efficacy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Immunomodulatory Drug

Abstract Lenalidomide is an immunomodulatory drug approved in the United States for use with rituximab in patients with relapsed/refractory follicular lymphoma. We reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory follicular lymphoma. Lenalidomide-rituximab has been demonstrated to be an effective chemotherapy-free therapy that improves upon single-agent rituximab and may become an alternative to chemoimmunotherapy.

Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 837-837 ◽  
Author(s):  
Ariel E Marciscano ◽  
Neel Gupta ◽  
Zhigang Zhang ◽  
Julie Teruya-Feldstein ◽  
Ariela Noy
Keyword(s):  
Follicular Lymphoma ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

A Systematic Review and Meta-Analysis of Radioimmunotherapy Consolidation for Untreated Patients with Follicular Lymphoma (FL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 101-101
Author(s):  
Adam C. Rose ◽  
Gia Garrett ◽  
Miray Seward ◽  
Pareen J Shenoy ◽  
Roy A Kucuk ◽  
...  
Keyword(s):  
Systematic Review ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Annual Meeting ◽  
Research Funding ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Cochrane Central Register ◽  
Inclusion Criteria ◽  
American Society

Abstract Abstract 101 Background: The disease course of FL is characterized by multiple relapses and progressively shorter response durations with subsequent therapies. As a result, numerous treatment strategies have been developed to reduce the risk of progression including consolidation with transplantation, radio-immunotherapy (RIT), or maintenance therapy with rituximab (R). At present, the optimal therapeutic strategy for FL patients (pts) remains undefined. R maintenance and RIT with an anti-CD20 antibody linked to iodine-131 (I131 Tositumomab) or to yttrium-90 (Y90-ibritumomab tiuxetan) have emerged as well tolerated treatments following induction. To quantify the benefits of consolidative RIT, we conducted a systematic review of the literature and a meta-analysis of selected studies. Methods: As part of a broader review, we searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue, 2011), MEDLINE (1/1966-6/2011), American Society of Hematology Annual Meeting abstracts (2004–2010), and American Society of Clinical Oncology Annual Meeting abstracts (2007–2010). Each database was searched using combinations of the term ‘follicular lymphoma' and the terms for treatment regimens. Inclusion criteria for studies were as follows: 1) reports on phase 2/3 studies; 2) n≥30; 3) previously untreated patients 4) treatment with RIT targeted at the CD20 antigen following an induction regimen; 5) original reporting in English of the following treatment outcome measures for pts with FL: CR/CR-unconfirmed, OR, and at least one form of survival data. Extracted data included pre-treatment disease status, pt characteristics, treatment regimen, progression free survival (PFS), overall survival (OS), complete response (CR) and overall response (OR). Pooled estimates of the CR rate, OR rate, 2-year PFS and 5-year PFS for pts treated with consolidative RIT were computed using DerSimonian and Laird random effects models. Results: Over 1136 records were reviewed with 8 studies meeting inclusion criteria with 556 patients. Between 1998 and 2007, pts were accrued at multiple sites in all but one study. Median ages ranged from 49–57 years with 41–61% male subjects, among the studies reporting gender. A weighted average of 97.2% of patients had stage III/IV disease with 73–98% pts having grade 1/2 disease, among those studies reporting histology. Among studies reporting this information, 19–44% of patients had abnormal LDH values, and 25–100% had bulky lymph nodes. CR rates ranged from 51% to 97%, 2-year PFS ranged from 65% to 86%, and 5-year PFS ranged from 38% to 67%. The pooled estimates of the CR rate and OR rate following consolidative RIT were 78% (95% CI 66%–87%) and 98% (95% CI 92.9%–99.5%), respectively (Figure A). The pooled estimates for the 2-year and 5-year PFS were 77.0% (95% CI 70.5–82.4%) and 56.0% (95% CI 41.9–69.2%), respectively (Figure B). Conclusions: This analysis suggests that consolidative RIT is beneficial to patients with previously untreated FL with meaningful CR rates and 5-year PFS. In addition, consolidative RIT compares favorably to maintenance therapy with R given after chemotherapy (ECOG 1496) in both 2-year PFS (77.0% vs. 73.5%) and 5-year PFS (56.0% vs. 46.4%), and needs to be compared to maintenance R following R-chemotherapy induction. Disclosures: Flowers: Genentech/Roche (unpaid): Consultancy; Celgene: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy; Novartis: Research Funding; Spectrum: Consultancy, Research Funding.

scholarly journals Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 1980-1986 ◽  
Author(s):  
Martine J. Piccart-Gebhart ◽  
Tomasz Burzykowski ◽  
Marc Buyse ◽  
George Sledge ◽  
James Carmichael ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Rates ◽  
First Line ◽  
First Line Therapy ◽  
Hazard Ratios

Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. Patients and Methods Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. Results Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. Conclusion Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

scholarly journals New developments in the treatment of follicular lymphoma/ marginal zone lymphoma (according to the Congress of the American Society of Hematology – 2020)

2021 ◽  
Vol 23 (1) ◽  
pp. 172-184
Author(s):  
Lali G. Babicheva
Keyword(s):  
Follicular Lymphoma ◽  
Anticancer Drugs ◽  
Marginal Zone ◽  
Negative Impact ◽  
Deep Understanding ◽  
Marginal Zone Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
American Society

Relevance. Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are the most common variants of indolent non-Hodgkin lymphoma (iNHL). Despite the adequate choice of the first-line therapy, 10 15% of affected patients with iNHL develop refractory disease, and in most of the cases the relapse of the disease among the others patients is detected, and each subsequent remission is shorter than the previous. According to the data of the National LymphoCare Study Group, the relapses that can occur during the first 2 years (POD24) after the beginning of the first-line therapy with R-CHOP in patients with FL, as well as with MZL, have a negative impact on the prognosis: 5-year overall survival in these patients decreases from 90 to 50%. The arsenal of therapy options is actively expanding along with a deep understanding of the biological basis of the disease development. At present, the most topical problem remains the choice of the best approach for each patient the personalization of the therapy. The review includes the data from clinical trials concerning FL and MZL treatment presented at the Congress of the American Society of Hematology in 2020. There are a large number of studies concerning new anticancer drugs in the world, such as monoclonal antibodies to different targets on the surface of B-cells, macrophages, bispecific antibodies, antibody conjugates, immunomodulators, BCR signaling pathway inhibitors (Bruton tyrosine kinase, PI3K inhibitors), immune checkpoint inhibitors and many others. Conclusion. The development of weighting approach for the choice of therapy will give a chance to patients with FL and MZL to stay alive up to the next era of new effective anticancer drugs. Future strategies, according to the current studies, show the trend away from the cytotoxic chemotherapy in iNHL therapy.

Outcomes of North American, Japanese, and European extensive-disease small cell lung cancer (ED-SCLC) patients under irinotecan-platinum or etoposide-platinum therapy: Systematic review and meta-analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18534-e18534
Author(s):  
Joao Paulo Da S.N. Lima ◽  
Andre Deeke Sasse ◽  
Emma C. Sasse ◽  
Lucas Vieira dos Santos
Keyword(s):  
Systematic Review ◽  
North American ◽  
Meta Analysis ◽  
Geographic Origin ◽  
First Line ◽  
First Line Therapy ◽  
Geographic Origins ◽  
One Year ◽  
Meta Analyses ◽  
The Impact

e18534 Background: Superiority of irinotecan-platinum (IP) regimens over etoposide-platinum (EP) in ED-SCLC has been extensively debated, with ethnic and pharmacogenomics issues hypothesized as causes of the divergent findings. We undertook a systematic review to scrutinize the data according to geographic origin. Methods: Randomized controlled trials comparing first-line EP doublets versus IP in ED-SCLC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), one-year survival, two-year survival, and safety. Meta-analyses were performed using random-effects model. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of geographical origin of study over the estimated effect size. Results: Seven studies (2,029 patients) were included. IP improved OS worldwide (HR = 0.83; 95% CI 0.76-0.92; P>0.001; I²=0%). However, the impact of IP on OS was different according to geographic origin, with relevant benefit for Japanese, little benefit for North American/Australian and intermediate for European patients (P for interaction = 0.029, table 1). One year survival was homogenously improved from 34% with EP to 40% with IP (P=0.006). IP improved two year survival just for Japanese and European patients but not to North American ones (Table). Toxicity was not impacted by trial origin. Conclusions: IP improved survival for both Western and Eastern patients, but seems to exist a gradient of benefit according to geographic origins, with maximal benefit for Japanese, some relevant for European ones and little, if any, for North American/Australian patients. These findings should be taken in account when considering IP or EP as first-line therapy for ED-SCLC patients worldwide. [Table: see text]

Systematic Review and Meta-Analysis of Radioimmunotherapy Regimens in Patients with Relapsed Follicular and Transformed Nonhodgkins Lymphomas.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3113-3113 ◽  
Author(s):  
Josiah N. Orina ◽  
Susan G. Moore ◽  
Mary Jo Lechowicz ◽  
Christopher R. Flowers
Keyword(s):  
Systematic Review ◽  
Follicular Lymphoma ◽  
Annual Meeting ◽  
Meta Analysis ◽  
Treatment Options ◽  
Response Rates ◽  
Inclusion Criteria ◽  
Cd20 Antibody ◽  
American Society ◽  
Hodgkin's Lymphomas

Abstract Background:Numerous treatment options are available to patients with relapsed follicular lymphoma(FL), ranging from watchful waiting to transplantation. At present, the optimal therapy for this patient population remains undefined. Single agent rituximab(R) and radioimmunotherapy(RIT) with anti-CD20 antibody linked to iodine-131 (I131 Tositumomab) or to yttrium-90 (Y90-ibritumomab tiuxetan) have emerged as well tolerated treatments for relapsed FL and other indolent B-cell non-Hodgkin’s lymphomas(NHL). In phase II and III trials, RIT has demonstrated higher rates of complete response(CR) and overall response(OR) in patients with relapsed FL. To quantify the benefit of RIT and compare this to R, We conducted a systematic review of the literature and a meta-analysis of selected studies. Methods:As part of a broader review, we searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 1, 2003), MEDLINE (1/1966-6/2005), EMBASE (1/1980-7/2005), American Society of Hematology Annual Meeting abstracts (2002–2004), and American Society of Clinical Oncology Annual Meeting abstracts (1995–2005). Each database was searched using combinations of the term follicular lymphoma and the terms for medications and treatment regimens. Inclusion criteria for studies were as follows: 1)Inclusion of patients with relapsed FL; 2)Treatment with RIT targeted at the CD20 antigen; 3)Original reporting in English of the following treatment outcome measures for patients with FL and/or other indolent NHL: CR/CR-unconfirmed, OR, and at least one form of survival data. Extracted data included pre-treatment disease status, patient characteristics, treatment regimen, progression free survival, overall survival, CR and OR. We utilized the Mantel-Haenszel (fixed effects model) and DerSimonain and Laird (random effects) methods to calculate the risk difference comparing the rates of CR/CRu and OR with RIT to those observed with conjugated CD20 antibody. For randomized trials of RIT the comparator in analyses was the control group from the trial. For other trials, response rates with RIT were compared to those observed with R in relapsed FL (McLaughlin, JCO 1998). Results:Over 1800 records were reviewed with 10 articles meeting inclusion criteria with 245 patients. Nearly all studies of RIT were multi-institutional, accrued patients between 1995 and 2002, had a median patient age &gt;50 years, and had 48%–68% male patients. Three studies did not specify the number of patients with indolent NHL by histological class. In the remainder, 65%–100% of patients had FL grade 1 or 2. The percentage of patients with FL grade 3 or transformed NHL ranged in studies from 0 to 25%. In comparison to unconjugated CD20 antibody, overall, RIT improved CR by 30% (95% CI:24%–37%) and improved OR by 42% (95% CI:35%–49%). I131- and Y90-based RIT had overlapping benefits. Conclusions:As suggested by the individual trials, RIT can improve the likelihood of response and CR compared with R. Selecting appropriate patients for RIT will require consideration of patient factors as well as future treatment options such as transplantation and maintenance therapy that may extend the benefits of these improved response rates. Figure Figure

Anti PD-(L)1 in KRAS mutant advanced nsclcs: A meta-analysis of randomized controlled trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9025-9025
Author(s):  
Thierry Landre ◽  
Gregoire Justeau ◽  
Jean-baptiste Assié ◽  
Kader Chouahnia ◽  
Chérifa Taleb ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Free Survival ◽  
Randomized Controlled ◽  
Meta Analyses ◽  
Review Manager

9025 Background: KRAS comprise the most frequently found oncogene driver mutation in non-small cell lung cancer (NSCLC), accounting for 20-25% of these patients. Single-agent Anti PD-(L)1 clinical efficacy against KRAS mutant NSCLC is a topic of debate. Methods: This meta-analysis examined randomized-trial data comparing first-or second line Anti PD-(L)1 +/- chemotherapy (CT) vs CT alone for KRAS mutant advanced NSCLCs. Outcome measures included overall survival (OS) and progression-free survival (PFS). Analyses were computed using the Cochrane method of collaboration for meta-analyses, with Review Manager software (RevMan version 5.3; Oxford, UK). Results: We analyzed 3 trials in first line (IMPOWER-150, KEYNOTE-189 and KEYNOTE-042), as well as 3 trials in second line (OAK, POPLAR and CHECKMATE-057) including 1313 NSCLCs (386 KRAS mutant and 927 KRAS wild-type tumor). Anti PD-(L)1 +/- CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.59 [0.49-0.72]; p < 0.00001) and PFS (0.58 [0.43-0.78]; p = 0.0003) compared to CT alone in KRAS mutant NSCLCs. Survival benefits occured in both first and second line. Survival benefits observed in KRAS wild-type NSCLCs were (0.87 [0.76-0.99]; p = 0.03) and (0.79 [0.56-1.11]; p = 0.17) respectively. OS benefit in KRAS mutant was significantly superior compared to OS benefit in KRAS wild-type (p = 0,001). Conclusions: Anti PD-(L)1 (+/- CT) appears superior to CT alone both for mutant and wild-type KRAS in advanced NSCLCs for OS and PFS with higher magnitude of benefit in KRAS mutated group for OS.

Sign in / Sign up

Export Citation Format

Share Document