scholarly journals Progression-free survival at 2 years post-autologous transplant: a surrogate end point for overall survival in follicular lymphoma

2017 ◽  
Vol 6 (12) ◽  
pp. 2766-2774 ◽  
Author(s):  
Ana Jiménez-Ubieto ◽  
Carlos Grande ◽  
Dolores Caballero ◽  
Lucrecia Yáñez ◽  
Silvana Novelli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Autologous Transplant ◽  
End Point

scholarly journals Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors

2016 ◽  
Vol 34 (21) ◽  
pp. 2478-2483 ◽  
Author(s):  
Darren R. Feldman ◽  
James Hu ◽  
Tanya B. Dorff ◽  
Kristina Lim ◽  
Sujata Patil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Collaborative Group ◽  
Intermediate Risk ◽  
First Line ◽  
Free Survival ◽  
Poor Risk ◽  
End Point

Purpose Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease. Patients and Methods In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m2 over 2 days, ifosfamide 6 g/m2 over 5 days with mesna support, and cisplatin 100 mg/m2 over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate. Results Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%. Conclusion TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.

The effect of statins on overall survival and progression-free survival in veterans with prostate cancer: A retrospective single-center experience.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 169-169
Author(s):  
Brian Warnecke ◽  
Raissa Lakene Djoufack Djoumessi ◽  
Juan Garza ◽  
Michael Mader ◽  
Shreya Chaudhary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
The United States ◽  
Inverse Association ◽  
Free Survival ◽  
End Point ◽  
Anti Cancer ◽  
Statin Use

169 Background: Prostate cancer is the most common cancer in men in the United States. Death in prostate cancer patients is often related to other medical conditions and not prostate cancer itself. Hence, it is important to optimize other co-morbidities, such as hyperlipidemia, hypertension, and cardiovascular diseases in these patients. However, there are numerous studies portraying the ability of statins to increase progression free survival and overall survival of prostate cancer. This has led to significant interest of statins having anti-cancer properties and ultimately improving long term outcomes. Methods: This is a retrospective observational study with chart review of 1,011 patients diagnosed with prostate cancer from 1995 to 2010 in a VA Hospital in San Antonio, Texas. Variables included age at diagnosis, statin use, type of statin (1st, 2nd, or 3rd generation), dose of statin (4 dosage levels), length of statin use, time followed in months (from diagnosis to death or end of study period), death, cause of death, and time to first progressive disease. Progressive disease was defined using PSWG2 guidelines which is PSA increase > / = 25% and at least 2ng/dl above the nadir. The Cox proportional hazards regression model was used to estimate the hazard function, with age, co-morbities and other cancers used as a covariate. End points were death by prostate cancer (56), death by any cancer (140), and death by all causes (484). We also looked at the effects of statins on progression free survival of prostate cancer. Results: The hazard ratio (HR) for use of statins and death by prostate cancer was 0.35, 95% confidence interval (CI): 0.20-0.62 (p = 0.0003), indicating that statin use has a statistically significant positive effect at delaying death by prostate cancer. Death by any cancer was significantly affected by statins with a HR of 0.47, 95% CI: 0.32-0.65 (p < 0.0001). Death by all causes was also affected significantly by statins with a HR of 0.64, 95% CI: 0.53-0.78 (p < 0.0001). Length of statin use, shorter versus longer than 4 years, showed an inverse association with our primary end point with a HR of 0.53, 95% CI: 0.40-0.69 (p < 0.0001). Dose level of statin, fourth level vs 1, 2, and 3, also showed an inverse association with our primary end point with a HR of 0.73, 95% CI: 0.57-0.94 (p = 0.014). Lastly, statin exposure significantly increased progression-free survival with a HR of 0.71, 95% CI: 0.53-0.95 (p < 0.021). Conclusions: It is clear that concomitant statin use increases overall survival in patients with prostate cancer, potentially even having anti-cancer protective effects against mortality. Longer duration of statin use and higher dose levels of statins increase length of overall survival in patients with prostate cancer. As mortality is often not due to prostate cancer, more interestingly, statin exposure is also shown to increase progression-free survival.

scholarly journals Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

2015 ◽  
Vol 33 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Qian Shi ◽  
Aimery de Gramont ◽  
Axel Grothey ◽  
John Zalcberg ◽  
Benoist Chibaudel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Individual Patient Data ◽  
Progression Free Survival ◽  
Patient Data ◽  
Biologic Agents ◽  
First Line ◽  
Free Survival ◽  
End Point

Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

Rituximab Added to Aggressive Chemotherapy Improves the Outcome of Patients with Follicular Lymphoma, Grade 3 and Results In Survival Comparable to Diffuse Large B-Cell Lymphoma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2810-2810
Author(s):  
Philip J. Bierman ◽  
Julie M. Vose ◽  
R. Gregory Bociek ◽  
Fausto R. Loberiza ◽  
Martin Bast ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
Grade 3

Abstract Abstract 2810 The survival of patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma is improved when rituximab is combined with chemotherapy. However, little is known about the outcome of patients with follicular lymphoma, grade 3 (FL-3), since these patients are generally excluded from DLBCL trials and often from trials evaluating treatment of follicular lymphoma. We therefore performed a retrospective study to evaluate the results of rituximab-based therapy for FL-3. An analysis of the Nebraska Lymphoma Study Group database allowed us to identify patients with FL-3 who were treated with aggressive combination chemotherapy regimens with and without the addition of rituximab. The progression-free survival (PFS) and overall survival of these patients were compared to patients with DLBCL who were treated with similar aggressive chemotherapy regimens combined with rituximab. Patients who were not treated with anthracycline-containing or mitoxantrone-containing regimens were excluded from analyses. We identified 60 FL-3 patients who were treated with aggressive chemotherapy regimens, combined with rituximab, between Feb. 1999 and Jan. 2009. The median age was 56 years (range 37–87 years). There were 27 males and 33 females. The performance status was 0–1 in 80%, the LDH was elevated in 15%, 68% had stage III-IV disease, and 13% had at least 2 sites of extranodal disease. Fifteen patients (25%) had bulky disease (≥5 cm) at diagnosis. The results of treatment for these patients were compared to 144 FL-3 patients treated with aggressive chemotherapy regimens without rituximab between June 1983 and Jan. 1999, and to 341 patients with DLBCL who were treated with aggressive chemotherapy regimens combined with rituximab between Sept. 1996 and Jan. 2009. The treatment outcomes for these three groups of patients are displayed in the table. 5-yr Estimate (95% CI) 8-yr Estimate (95% CI) Log-Rank p-value Progression-Free Survival 0.04 FL-3 with rituximab 65% (50–77) 45% (23–65) FL-3 without rituximab 42% (34–50) 33% (26–41) DLBCL with rituximab 53% (47–58) 47% (40–54) Overall Survival 0.06 FL-3 with rituximab 85% (72–92) 71% (54–82) FL-3 without rituximab 68% (59–74) 54% (46–62) DLBCL with rituximab 64% (58–69) 56% (48–63) A multivariate analysis (accounting for older patients, and more patients with elevated LDH, extranodal disease, and bulky disease in the DLBCL group) revealed that patients with FL-3 who were not treated with rituximab had a significantly higher risk of disease progression or death (RR 1.75; p=0.02). There were no significant differences in PFS when comparing patients with FL-3 and those with DLBCL who were treated with aggressive chemotherapy regimens and rituximab. Follicular lymphoma, grade 3 patients treated without rituximab had inferior overall survival, when compared to patients treated with rituximab (RR 1.58), although this difference was not significant (p=0.16). The multivariate analysis also revealed no significant differences in survival when patients with FL-3 who received rituximab were compared to similarly treated patients with DLBCL (p=0.50). In conclusion, this analysis demonstrates that the outcome of treatment for patients with FL-3 who are treated with aggressive chemotherapy regimens is improved when rituximab is added to therapy. In the “rituximab era” the outcome of patients with FL-3 is comparable to DLBCL. Disclosures: Vose: Millennium Pharmaceuticals, Inc.: Research Funding.

Rituximab Purging and Maintenance Improves Progression Free Survival but Not Overall Survival In Patients with Relapsed or Resistant Follicular Lymphoma Prior Receiving An Autologous Transplant

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3567-3567 ◽  
Author(s):  
Ruth Pettengell ◽  
Norbert Schmitz ◽  
Christian Gisselbrecht ◽  
Graeme Smith ◽  
William N Patton ◽  
...  
Keyword(s):  
Overall Survival ◽  
Peripheral Blood ◽  
Research Funding ◽  
Progression Free Survival ◽  
Phase Ii Trials ◽  
Free Survival ◽  
Post Transplant ◽  
Autologous Transplant

Abstract Abstract 3567 Autologous transplantation significantly improves the progression free survival (PFS) and overall survival (OS) of patients with relapsed or resistant follicular (rFL) lymphoma compared with chemotherapy alone (Schouten H, et al. J Clin Oncol 2003;21:3918–27). Small phase II trials suggest, that rituximab (R) given peritransplant further improves survival outcome. Whilst the role of maintenance R post chemotherapy in FL is established, the benefit and safety of maintenance R following autologous transplant is unknown. In this randomised prospective study the efficacy and safety of R as in vivo purging pretransplant and as maintenance treatment immediately post transplant was assessed. From Oct 1999 to Apr 2006, 280 of a planned 420 R naïve patients with rFL in first (n=16), second (n= 222) or third remission (n=41) who achieved either a complete remission (n=83) or a very good partial remission (n=196) to induction chemotherapy, with limited bone marrow infiltration (<25% B-lymphocytes) underwent a single randomisation in a 2 × 2 design to R purging 375 mg/m2 weekly × 4 (RP) before high-dose therapy with BEAM conditioning (HDC) and maintenance R 375 mg/m2 every 3 months for 2 years (RM). The primary endpoint of the study was PFS. All analysis is by intention to treat. The median age was 51 years (range: 26–70), and baseline characteristics were well balanced between groups. On average patients were 44.1 (range 3.4–463.8) months from diagnosis with 79.3% having 2 lines of therapy and 15% three lines of prior therapy. Patients were equally distributed between low, intermediate and high FLIPI scores. Pretransplant 70% of patients were in PR and 30% in CR. Fifty seven patients failed to mobilise peripheral blood stem cells. Nineteen patients withdrew, 5 due to toxicity, 9 were ineligible. In the 196 (70%) patients transplanted, neutrophil engraftment > 0.5 × 109 /L was prompt, median 14.3 days (range 10–115) and platelets > 50 × 109/L,median 25.1 days (range 9–190). Time to engraftment and early or late toxicities did not differ significantly between the groups apart from a lower neutrophil count at 3 months in patients on maintenance. No graft failures or late neutropenia was reported. Transplant related mortality was 0.5%. Only 3 infection related deaths have been reported post 100 days. Two hundred and seventeen patients are alive on continued follow-up. Median follow-up is 6.4 years. PFS at 5 years was 62.9% for patients receiving RP + RM versus 37.6 % for patients receiving no R (logrank PFS; p=0.004; HR 0.76, 95%CI: 0.66 – 0.93). OS at 5 years was 79.5% % versus 78.4 % for patient receiving RP + RM versus no R (logrank PFS; p>0.1). Multivariate analysis was not able to define a high or low risk patient group. R in vivo purging and maintenance results in superior PFS compared to no R. R does not adversely affect peripheral blood stem cell harvesting or engraftment and maintenance R post transplant is safe. The impressive OS suggests that relapsed FL patients can be effectively salvaged post R purging and maintenance. R Purging + R Maintenance R Maintenance R Purging No R Pt number 69 69 72 70 Median PFS NR@ 6.4 y 7.23 y 4.03 y 3.34 y 5y PFS 62.9 % 56 % 46 % 37.6 % 5y OS 79.5 % 80.5 % 84.8 % 78.4 % Disclosures: Pettengell: Roche: Honoraria. Schmitz:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gisselbrecht:Roche: Research Funding. Walewski:Roche: Honoraria, Research Funding. Geisler:Roche: Research Funding. Kimby:Roche: Honoraria, Research Funding. Goldstone:Roche: Honoraria, Speakers Bureau.

Management of Grade 3B Follicular Lymphoma (FL) Outside Clinical Trials: A Multicentric Retrospective Analysis on Behalf of Fondazione Italiana Linfomi (FIL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2716-2716
Author(s):  
Barbara Botto ◽  
Federica Cavallo ◽  
Manuela Zanni ◽  
Antonella Anastasia ◽  
Chiara Rusconi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
First Line Treatment

Abstract Introduction: Follicular lymphoma grade 3 is recognized as a distinct entity in the World Health Organization classification of lymphoma. It is further classified into grade 3a and 3b depending on percentage of centroblasts. There is no consensus about its clinical course because some studies indicate an indolent behavior but others describe a more aggressive. Large systematic studies are missing in particular for 3b follicular lymphoma which is often considered as a separate entity. Methods: We performed a retrospective multicentric study on a group of 3b FL patients diagnosed in nine Italian FIL centers between November 2002 and January 2015. Planned inclusion criteria at enrollment were first line Rituximab containing regimen treatment and diagnostic samples availability for central pathologic review. Aim of the study was to determine clinical response, OS and PFS. Tumor response was based on the International Working Group response criteria. Survival analysis was performed with Kaplan-Meier method. Results: We enrolled a total of 51 patients, 50 evaluable for response at the time of analysis; median age was 62 yrs (range 48-71), 29 (56%) in stage III-IV, 10 (20%) with B symptoms. First line treatment was R-CHOP in the majority of patients 47 (92%), R-Bendamustine and R-CVP in 2 (4%) respectively. Seven patients (14%) received Rituximab maintenance after first line, six (12%) underwent high dose chemotherapy and autologous stem cell transplant (ASCT) as consolidation therapy and 5 (10%) were treated with local radiotherapy on residual disease. We observed CR in 48 patients (96%), PR in 1 (2%), PD in 1(2%). Ten patients relapsed or progressed after first line treatment and four of them died, three for progressive disease and one due to senile dementia while in CR. No relapses were recorded in pts receiving Rituximab maintenance but the advantage was not statistically significant and the number of patients receiving maintenance was low. With a median follow up of 63 months from diagnosis (IQR 33-82), 3-yrs PFS and OS rates were 82% and 93% (fig 1 and 2) with the evidence of a plateau in both survival curves after 5 years observation. Central pathologic review is ongoing. Conclusion: With the limit of a retrospective analysis our study confirms the clinical benefit of a combined modality treatment with Rituximab plus antracycline-containing chemotherapy in patients with 3b FL. Our results compare favorably with those previously reported in studies without Rituximab, that failed to show a plateau with 3-yrs PFS ranging between 22% and 52%. This results need to be confirmed with a longer follow up and after the planned pathologic review. Figure 1. Progression-Free Survival. Median Follow-up 62 months (IQR 33-82). Figure 1. Progression-Free Survival. Median Follow-up 62 months (IQR 33-82). Figure 2. Overall Survival. Median Follow-up 63 months. Figure 2. Overall Survival. Median Follow-up 63 months. Disclosures No relevant conflicts of interest to declare.

Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 0801

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 614-614
Author(s):  
Paul M. Barr ◽  
Hongli Li ◽  
Richard Burack ◽  
Michael LeBlanc ◽  
Sonali M. Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Free Survival ◽  
Grade 3

Abstract Background: Despite an abundance of effective therapeutic options, advanced stage follicular lymphoma (FL) remains incurable. Further, prospective trials consistently demonstrate that 20% of patients relapse within 2 years and ultimately have an inferior survival (Casulo 2015). Maintenace rituximab following chemoimmunotherapy induction is able to delay disease progression but has not demonstrated a benefit in overall survival (Salles 2011). Additionally, radioimmunotherapy (RIT) is one of the most effective single agent options in FL but is not commonly utilized as part of upfront treatment. As such, the role of both remains unclear. Based on results demonstrated with RIT consolidation in SWOG 0016 and the efficacy of rituximab maintenance, SWOG 0801 was designed as a phase 2 single arm trial, conducted to evaluate the utility of consolidative RIT and sequential maintenance rituximab following chemoimmunotherapy induction. Methods: Eligible patients (pts) with treatment naïve stage III/IV or bulky stage II FL received RCHOP for 6 cycles (without rituximab for the last 2 cycles) followed by iodine-131 tositumomab and subsequent rituximab administered every 3 months for up to 4 years. The primary endpoint was progression-free survival (PFS) at 3 years. Secondary endpoints included 5-year overall survival (OS), overall response rate (ORR), and safety. Results: Of 87 pts registered to this study, 85 were deemed eligible following central pathologic review. One additional patient withdrew consent and received no treatment on protocol. Of the 84 evaluable patients, the median age was 52 years (range 29 - 80) ) and 18%, 40%, and 42%had low, intermediate and high risk FLIPI scores, respectively. Seventy-three pts completed RCHOP and I-131 tositumomab. Grade ≥3 AEs occurring ≥5% of pts included neutropenia (57%), leukopenia (40%), thrombocytopenia (20%), febrile neutropenia (17%), fatigue (10%), neuropathy (8%), anemia (7%) and hyperglycemia (5%). Reasons for discontinuation included refusal of tositumumab (6 pts), prolonged myelosuppression (2 pts), ascites (1pt), inability to provide tositumumab (1 pt), and an unrelated lower extremity wound (1 pt). Following induction and RIT, 59 complete responses and 23 partial responses were observed, for a ORR of 99% (95% CI: 93.5%, 99.9%) Sixty nine eligible patients registered to maintenance therapy with 42 completing the 4 year treatment plan. The only grade ≥3 AE that occurred in ≥5% of pts was leukopenia (5%). Twenty-seven pts discontinued maintenance therapy, including 11 in the first 2 years and 16 in the last 2 years, due to the following reasons: infection (8 pts), patient preference (8 pts), deaths (2 pts), treatment delay (2 pts), secondary solid tumors (2 pts), bowel perforation (1 pt), joint pain (1 pt), hepatic transaminase elevation (1 pt), insurance refusal (1 pt), and dose error (1 pt). Four additional secondary malignancies were reported following completion of therapy including solid tumors (3 pts) and AML (1 pt). To date, 9 deaths have occurred due to secondary malignancies (3 pts), unknown etiology (3 pts), cardiac arrest (2 pts) and non-alcoholic cirrhosis (1 pt). After median follow-up of 5.6 years (range 3-7 years), 17 events have occurred including 9 pts experiencing progressive FL resulting in a progression free survival of 90% (95% CI: 81.9%, 95.1%) at 3 years and 84%(95% CI: 74.5%, 90.6%) at 5 years (Figure). Three-year overall survival is 96% (95% CI: 89.3%, 98.8%) and 5-year overall survival is 94% (95% CI: 86.2%, 97.5%). Conclusions: SWOG 0801 demonstrates near universal responses following chemoimmunotherapy and RIT. This sequential therapeutic strategy appears to improve early outcomes as 94% of pts are without disease progression at 2 years, consistent with the best results ever demonstrated for FL in the National Clinical Trials Network. However, the majority of discontinuations occurred during maintenance suggesting that rituximab over a 4-year span is not feasible for many patients due to cumulative toxicity. Future studies investigating precision strategies in high-risk FL may consider an aggressive chemoimmunotherapy induction and RIT consolidation platform to overcome early FL progression given these promising outcomes. Support: NIH/NCI grants CA180888, CA180819, and in part by GlaxoSmithKline. Figure. Progression-Free Survival and Overall Survival Figure. Progression-Free Survival and Overall Survival Disclosures Barr: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Smith:Amgen: Other: Educational lecture to sales force; Juno: Consultancy; Pharmacyclics: Consultancy; AbbVie: Consultancy; Portola: Consultancy; Celgene: Consultancy; Gilead: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; TGTX: Consultancy. Gopal:Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy. Persky:Merck: Research Funding; Gilead: Speakers Bureau. Press:Roche / Genentech: Consultancy, Research Funding. Fisher:Gilead: Consultancy; Seattle Genetics: Consultancy; Johnson and Johnson: Consultancy. Friedberg:Bayer: Other: Data Safety Monitoring Committee.

scholarly journals Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03

2016 ◽  
Vol 34 (5) ◽  
pp. 495-500 ◽  
Author(s):  
Christian Taverna ◽  
Giovanni Martinelli ◽  
Felicitas Hitz ◽  
Walter Mingrone ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Short Term ◽  
End Points ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
End Point ◽  
Unacceptable Toxicity

Purpose Rituximab maintenance therapy has been shown to improve progression-free survival in patients with follicular lymphoma; however, the optimal duration of maintenance treatment remains unknown. Patients and Methods Two hundred seventy patients with untreated, relapsed, stable, or chemotherapy-resistant follicular lymphoma were treated with four doses of rituximab monotherapy in weekly intervals (375 mg/m2). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of 5 years or until disease progression or unacceptable toxicity). The primary end point was event-free survival (EFS). Progression-free survival, overall survival (OS), and toxicity were secondary end points. Comparisons between the two arms were performed using the log-rank test for survival end points. Results One hundred sixty-five patients were randomly assigned to the short-term (n = 82) or long-term (n = 83) maintenance arms. Because of the low event rate, the final analysis was performed after 95 events had occurred, which was before the targeted event number of 99 had been reached. At a median follow-up period of 6.4 years, the median EFS was 3.4 years (95% CI, 2.1 to 5.3) in the short-term arm and 5.3 years (95% CI, 3.5 to not available) in the long-term arm (P = .14). Patients in the long-term arm experienced more adverse effects than did those in the short-term arm, with 76% v 50% of patients with at least one adverse event (P < .001), five versus one patient with grade 3 and 4 infections, and three versus zero patients discontinuing treatment because of unacceptable toxicity, respectively. There was no difference in OS between the two groups. Conclusion Long-term rituximab maintenance therapy does not improve EFS, which was the primary end point of this trial, or OS, and was associated with increased toxicity.

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer

2019 ◽  
Vol 29 (7) ◽  
pp. 1141-1147 ◽  
Author(s):  
Domenica Lorusso ◽  
Felix Hilpert ◽  
Antonio González Martin ◽  
Joern Rau ◽  
Petronella Ottevanger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Patient Reported Outcomes ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Free Survival ◽  
End Point ◽  
Platinum Resistant ◽  
Patient Reported ◽  
Epidermal Growth

IntroductionThe PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes.Patients and methodsEligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression.ResultsAt database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms.DiscussionConsistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes.ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878.

scholarly journals Evaluation of Two Dosing Regimens for Nivolumab in Combination With Ipilimumab in Patients With Advanced Melanoma: Results From the Phase IIIb/IV CheckMate 511 Trial

2019 ◽  
Vol 37 (11) ◽  
pp. 867-875 ◽  
Author(s):  
Celeste Lebbé ◽  
Nicolas Meyer ◽  
Laurent Mortier ◽  
Ivan Marquez-Rodas ◽  
Caroline Robert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Melanoma ◽  
Free Survival ◽  
End Point ◽  
Phase Iiib ◽  
Grade 3

PURPOSE Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (NIVO1+IPI3) is approved for first-line treatment of patients with advanced melanoma in several countries. We conducted a phase IIIb/IV study (CheckMate 511) to determine if nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (NIVO3+IPI1) improves the safety profile of the combination. PATIENTS AND METHODS Patients (N = 360) age 18 years or older with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to NIVO3+IPI1 or NIVO1+IPI3 once every 3 weeks for four doses. After 6 weeks, all patients received NIVO 480 mg once every 4 weeks until disease progression or unacceptable toxicity. The primary end point was a comparison of the incidence of treatment-related grade 3 to 5 adverse events (AEs) between groups. Secondary end points included descriptive analyses of objective response rate, progression-free survival, and overall survival. The study was not designed to formally demonstrate noninferiority of NIVO3+IPI1 to NIVO1+IPI3 for efficacy end points. RESULTS At a minimum follow-up of 12 months, incidence of treatment-related grade 3 to 5 AEs was 34% with NIVO3+IPI1 versus 48% with NIVO1+IPI3 ( P = .006). In descriptive analyses, objective response rate was 45.6% in the NIVO3+IPI1 group and 50.6% in the NIVO1+IPI3 group, with complete responses in 15.0% and 13.5% of patients, respectively. Median progression-free survival was 9.9 months in the NIVO3+IPI1 group and 8.9 months in the NIVO1+IPI3 group. Median overall survival was not reached in either group. CONCLUSION The CheckMate 511 study met its primary end point, demonstrating a significantly lower incidence of treatment-related grade 3-5 AEs with NIVO3+IPI1 versus NIVO1+IPI3. Descriptive analyses showed that there were no meaningful differences between the groups for any efficacy end point, although longer follow up may help to better characterize efficacy outcomes.

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