scholarly journals Multiple Myeloma: Where Do We Lose Ground Along the Treatment Pathway?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Dharmini Manogna ◽  
Bassil Said ◽  
Naman Sharma ◽  
Fateeha Furqan ◽  
Jonathan Bress ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Logistic Regression ◽  
High Risk ◽  
Binary Logistic Regression ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Negative Predictor

Introduction: Despite progress made in the treatment of multiple myeloma (MM), a significant percentage of patients are unable to receive second line of therapy. Our study evaluated the burden of infectious complications, and other factors that may play a role in hindering patients from receiving subsequent lines of therapy at a comprehensive teaching hospital. Methods: Patients with MM treated between 2014 and 2019 at Rochester General Hospital were selected from the MM registry. Tool was designed on REDCap for retrospective data collection from electronic medical records. Patients who declined therapy, never received treatment, had smoldering myeloma, or with a concomitant immunocompromising state were excluded. Out of 159 patients, 119 were eligible for analysis. We studied the relationship between patient demographics, clinical characteristics, treatment regimens, and outcomes. Binary logistic regression was used to determine which factors were significant in determining advancement in the line of treatment. The chi-squared statistic was used to determine significance with a Type I error rate set at 0.05. Results: The median age at diagnosis of MM was 68.5 years (Interquartile range=59.2-76.9), 55.4% (n=66) were males, 72.3% (n=86) were Caucasian. Revised International Staging System (R-ISS) staging was available for 77 patients, 27.3% (n=21) were stage I, 58.4% (n=45) were stage II, and 14.3% (n=11) were stage III. Cytogenetics were available for 93 patients, 76.3% (n=71) were standard risk and 23.7% (n=22) were high risk [17p del, t(4;14) or t(4;16)]. A three-drug induction regimen was administered to 61.3% (n=73) patients. Autologous stem cell transplant was performed in 39.5 % (n=47). Sixty-seven patients (56.3 %) received second line therapy. Twenty-six patients did not have a relapse after the first line at the time of data censorship. Patients who did not receive a second line treatment after relapse or progression were 21.8% (n=26). The factors prohibiting proceeding to a second line regimen (can be multiple) included patient preference/poor performance status (n=15), death while on first line treatment (n=15), advanced age (n=6) and prohibitive co-morbidity (n=4). Binary logistic regression showed age to be a significant negative predictor for receiving second line therapy. The odds ratio (OR) of receiving second line therapy was 0.88 for every year increase in age, 95% CI (0.78-0.95), p=0.007 (Figure 1). One or more documented infections within 6 months of diagnosing MM or until transplant date occurred in 32.8% (n=39). Types of infections are depicted in Figure 2. Documented infection was a borderline significant negative predictor for receiving second line therapy with OR =0.23, 95% CI (0.05-1.003), p=0.059. Race, pre-existing chronic kidney disease (CKD), gender and high-risk cytogenetics were not significant predictors of receiving second line therapy (Figure 1). Conclusion: Our study identified advancing age as a significant negative predictive factor to receipt of second line therapy in MM. Documented infections, while borderline significant, had a high impact as to whether a patient receives second line therapy. Strategies such as a formalized geriatric assessment, tailored treatment for frail patients, and infection prevention measures might increase odds of receiving second line therapy and may result in improved outcomes. Disclosures Jamshed: Takeda, Amgen and Celgene: Honoraria.

Risk of Progression and Survival in Newly Diagnosed Multiple Myeloma Patients Non-Responsive to Bortezomib-Based Induction Therapy: an Observational Multicenter International Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3488-3488
Author(s):  
Yael C Cohen ◽  
Erel Joffe ◽  
Noam Benyamini ◽  
Meletios A. Dimopoulos ◽  
Svetlana Trestman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Disease Progression ◽  
Line Treatment ◽  
Second Line ◽  
Newly Diagnosed ◽  
Inclusion Criteria ◽  
First Line ◽  
Line Therapy ◽  
Induction Regimen

Abstract INTRODUCTION Botezomib-based induction is widely used and highly effective for the treatment of patients with newly diagnosed multiple myeloma (NDMM), with an overall response rate (ORR) of 75-80%. However, the outcomes of patients who fail to respond to this treatment remain unclear. The goal of this study was to investigate the outcome of patients with NDMM who failed to respond to bortezomib-based induction as compared to induction-responsive patients. METHODS We reviewed consecutive patients with NDMM between 1-JAN-2007 and 31-JAN-2014 in three participating centers in Greece and Israel. Inclusion criteria were measurable disease and an induction regimen containing bortezomib in combination with alkylators and/or corticosteroids. Patients who failed to achieve at least partial response in accordance with IMWG criteria after 4 cycles of therapy were classified as non-responsive and their baseline characteristics, next treatment, overall survival and progression following second-line treatment (2ndPFS) were assessed and compared to responsive patients. 2ndPFS was defined as the time from 2nd line treatment to disease progression, death or censoring. In the non-responsive group we limited this analysis to patients advancing to 2nd line within six months of initiation of induction. RESULTS Two hundred and ninety five patients met inclusion criteria and 74 (25%) were non-responsive to bortezomib-containing induction. Non-responsive patients were older, more anemic and had more often ISS-3, del17p and ECOG performance status 2-4 (table 1). Notably, these patients received less often a bi-weekly bortezomib schedule, a triple-drug regimen and high dose melphalan treatment at first line. Of the non-responsive patients 57% (n=42) received salvage treatment immediately following induction non-response, with an ORR of 59% (25/42); 12/31(39%) of those treated with salvage 2nd line and 13/15(87%) of those who underwent HDM at first line, responded. Failure to respond to bortezomib induction was associated with increased mortality (HR 5.06, 95% CI 2.80 – 9.16) (Fig. a), which remained significant in multivariate analysis. One- and 3-years OS in responsive vs. non-responsive patients were 97% vs 76% and 88% vs 53%, respectively (p<0.0001). 2ndPFS in patients who received salvage second line therapy immediately following induction failure was similar to that measured in bortezomib-responsive patients receiving 2nd-line therapy for disease progression, approaching 14 months. However, survival from time of salvage 2nd-line treatment was significantly lower among patients non-responsive to bortezomib-based induction compared to that measured in responsive patients (25 months vs. not reached, respectively, p=0.024; Fig. b). CONCLUSIONS Failure to respond to a bortezomib-based induction was found to be an independent risk factor for mortality. Despite the non-inferior 2ndPFS reported in these patients as compared with their bortezomib-responsive counterparts, survival remained significantly inferior. Possibly this difference is because non-responsive patients are less likely to respond to further proteasome inhibitor therapy at following relapses. Randomized controlled trials are needed to test whether intensification of induction and/or of further treatment may improve the poor prognosis of patients who fail to respond to bortezomib-based induction. Table 1: All patients n = 295 Induction non-responsive n = 74 Induction - responsive n =221 P value Demographic Median Age (yrs) 62.0 66.8 61.0 0.004 Gender Male Female 148 (50%) 147 (50%) 42 (55%) 33 (45%) 107 (48%) 114 (52%) 0.347 Patient / Disease ECOG 0-1 2-4 182 (63%) 107 (37%) 33 (45%) 40 (55%) 149 (69%) 67 (31%) <0.0001 ISS I II III 74 (28%) 95 (36%) 95 (36%) 9 (14%) 20 (33%) 33 (53%) 65 (32%) 75 (37%) 62 (31%) 0.002 High risk Cytogenietics Del17p High risk (%) Elevated LDH (%) Extramedullary disease (%) Hb≤ 10 gr% Creatinine > 2mg% 23 (14%) 69 (34%) 66 (27%) 23 (9.5%) 114 (43%) 64 (23%) 10 (26%) 13 (28%) 21 (36%) 5 (8.1%) 35 (54%) 20 (30%) 13 (10%) 56 (36%) 45 (24%) 18 (9.7%) 79 (39) 44 (21%) 0.031 0.297 0.091 0.805 0.044 0.094 Therapy Induction regimen VCD Vd VMP PAD 204 (69%) 49 (17%) 11 (4%) 19 (6%) 52 (57%) 18 (24%) 3 (4%) 4 (5%) 162 (73%) 31 (14%) 8 (4%) 15 (7%) 0.007 Any triplet 243 (82%) 55 (74%) 188 (85%) 0.051 Bortezomib schedule Bi-weekly Weekly 239 (81%) 56 (19%) 52 (70%) 22 (30%) 187 (85%) 34 (15%) 0.010 HDM at first line 143 (48%) 15 (20%) 128 (58%) <0.0001 Figure 1 Figure 1. Disclosures Dimopoulos: Celgene: Consultancy, Honoraria.

The Outcome of Different Types of Second-Line Therapy in Multiple Myeloma Patients Relapsing After Uniform Front-Line Treatment with High-Dose Melphalan and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2892-2892
Author(s):  
Claudia Crippa ◽  
Samantha Ferrari ◽  
Monica Drera ◽  
Marinella Calarco ◽  
Antonio Regazzoli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Dose ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
High Dose Melphalan

Abstract Abstract 2892 Poster Board II-868 Background and aim. While multiple myeloma (MM) still remains largely incurable, therapeutic options for patients with MM are expanding. However the best way to use the different effective regimens, either in combination or in sequence, during the course of MM in the single patient is still unknown. Data from controlled studies rarely report the treatments received before and after the enrollment of patients in the clinical trial, which may significantly impact on response and survival. As an example, the best treatment for patients relapsing after first-line high-dose melphalan (HD-Mel) and autologous stem cell transplantation (ASCT) is not standardized. To this end we have retrospectively analyzed an uniform cohort of such patients treated at our Institution, comparing their outcome according to the type of second-line and further consolidation treatment received. Patients and methods. In 156 patients affected by MM and treated between 1997 and 2008 with HD-Mel and ASCT as first line therapy, relapse has occurred in 92 (59%). Females were 39 (42%), males 53 (58%), median age was 60 (range 34-75). As induction therapy before ASCT, 89 (97%) had received VAD regimen, and only 3 (3%) thalidomide/bortezomib-based regimen. Sixty-one patients (66%) had received a single ASCT and 31 a double ASCT (34%). A second-line therapy was given to 87/92 patients. They were subdivided in 3 subgroups according to the type of second-line treatment received: 1) thalidomide-based regimens (THAL) were given to 55 pts (63%) followed by a consolidation ASCT in 13 (24%) 2) bortezomib-based regimens (BORT) were used in 13 (15%) and subsequent ASCT in 3 of them (23%) 3) chemotherapy and/or steroids (CHEMO) were used in 19 (22%) followed by ASCT in 15 (79%). Median follow-up from diagnosis was 57 (13-145) in THAL, 39 (17-140) in BORT and 59 months (25-113) in CHEMO respectively. The baseline characteristics, including age, of the three subgroups were similar as well as the CR/VGPR and ORR rates obtained after first-line treatment (THAL 47% and 87%; BORT 69% and 100%; CHEMO 53% and 100%, respectively). The subgroups also did not differ in median duration of first response, which ranged from 13 to 15 months and median time to second treatment, which was 26 months in all subgroups. The proportion of patients receiving a double ASCT were significantly higher in BORT (69%) compared to THAL (34%) (P=0.03) and CHEMO (5%) (p=0.002), and in THAL (34%) compared to CHEMO (5%) (p=0.015). Results. After second line therapy the ORR (CR+VGPR+ PR) of the three subgroups was: THAL 60%, BORT 77% and CHEMO 58%. (p=NS). The second CR/VGPR rate was non significantly higher after BORT (46%) than after THAL (25%) or CHEMO (21%) (p=0.17). Moreover, when considering patients not undergoing second-line consolidation ASCT, the ORR was significantly better in THAL and BORT subgroups compared to CHEMO (50%, 70% and 0%, respectively p=0.03). After a median follow-up from second-line treatment of 28 months (range 1-99), the 2-y PFS was 38% after THAL (median 18 months), 34% after BORT (median 16 months) and 17% after CHEMO (median 12 months) (p=NS). The 2-y OS was 78% (median 49 months), 70% (median not reached), and 70% (median 33 month) after THAL, BORT and CHEMO, respectively (p=NS). However when considering patients not undergoing second-line consolidation ASCT, the 2-y OS was significantly better after THAL and BORT than after CHEMO (p=0.024). Conclusion. In spite of having frequently received a first-line double ASCT, BORT patients seemed to achieve responses of better quality. However, in patients relapsing after first-line HD-Mel and ASCT, the choice of THAL, BORT or CHEMO-based regimens as second-line therapy did not seem to impact on overall response rates and survival, provided that patients treated with CHEMO could be consolidated with a second ASCT. Hence newer drugs may be reserved for those patients not fit for ASCT, preserving them for effective third-line treatment in the other patients. Disclosures: No relevant conflicts of interest to declare.

Retreatment Patterns and Outcomes Among Patients with Relapsed Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5935-5935
Author(s):  
Lincy S Lal ◽  
Benjamin J Chastek ◽  
Cori Blauer-Peterson ◽  
Eric M Maiese
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Index Date ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Risk Of Death ◽  
Line Therapy ◽  
Line Of Therapy

Abstract Introduction: Clinical trials have suggested that retreatment with multiple myeloma (MM) therapy provides clinical benefit (Mohty 2012), however, little is known about real-world utilization and outcomes of retreatment. Information from this analysis will help to better understand the real-world impact of retreatment for management of first MM relapse. Methods: A retrospective claims analysis of commercial and Medicare Advantage patients aged 18 years in the Optum Research Database. To be included, patients had to have ≥ 2 medical claims ≥ 30 days apart with an MM diagnoses (ICD-9 =203.00) between 01 Jan 2009 and 31 Dec 2013 (study period); ≥ 2 lines of therapy and no evidence of hematopoietic cell transplant during the study period and data available for 1 year prior to index date and ≥ 6 months post index date. The date of the first claim of an NCCN recommended MM treatment during the study period was considered the index date. All MM treatments identified < 30 days of the index date were considered part of first line of therapy. An algorithm was developed for identifying subsequent lines of therapy. A new line of therapy was identified when there was a switch to a new agent < 180 days of discontinuation of the prior line of therapy or retreatment with the same treatment ≥ 180 days of discontinuation with previously used agents. Additionally, patients had to be treated for relapse MM defined according to lines of therapy when 1) there was an active line of therapy ≥ 60 days long and there was a gap of ≥ 180 days from the end of the line of active therapy to the start of the next line of active therapy or 2) there was a line of therapy ≥ 180 days long and a different treatment was started, with or without a 180-day gap between discontinuation of the prior line and start of the subsequent line of therapy . The data evaluated in the analysis included baseline demographics, Quan-Charlson comorbidity scores, line of therapy, and clinical outcomes, including treatment duration and overall survival. Data were analyzed using chi-square and t-tests to compare patients with retreatment vs. treatment with a different regimen for first relapse MM (i.e. second-line therapy). Results: A total of 252 patients (mean age: 70 yrs; 48% male) were identified as having second-line treatment for relapse MM; 90 patients (35.7%) were retreated with the same regimen and 162 (64.3%) patients were treated with a different regimen. Mean Quan-Charlson comorbidity scores were equal between the two groups (p=0.585). Among the retreatment group, 48.2% were treated with monotherapy for first-line, compared to 25.2% of the different regimen group (p-value < 0.001). Dexamethasone (dex) monotherapy, bortezomib plus dex, and lenalidomide plus dex were common regimens used in retreatment, see Figure 1. Lenalidomide plus dex was also commonly used as a different regimen for second-line treatment. Additionally, dex monotherapy was significantly less likely to be used as a new therapy compared to being used as retreatment for second-line therapy (p<0.05). Conversely, bortezomib plus lenalidomide plus dex was significantly more likely to be used as a new therapy compared to being used as retreatment for second-line treatment (p<0.05). The mean length of relapse line was 161 days in the retreatment group versus 212 days in the different regimen group (p-value 0.067). The incidence rate of death was 13 events (1.43 events per 10,000 person-days of follow-up) in the retreatment group versus 22 events (1.51 events per 10,000) in the different regimen group (p=0.895). Figure 1: Second-line Treatment Regimens among Patients who Received the Same Regimen (Retreatment) vs. a Different Regimen for the Treatment of First-Relapse MM\s Conclusions: In this analysis, approximately one-third of patients were retreated with the same treatments in first-line and second-line of therapy. Patients who were retreated with the same regimen tended to have shorter duration of second-line therapy. However, risk of death did not appear to differ between the two groups. This real-world analysis suggests that retreatment in second-line may affect the time to next treatment, but may not negatively impact the overall risk of death. Reference: Mohty B, El-Cheikh J, Yakoub-Agha I, et al. Treatment strategies in relapsed and refractory multiple myeloma: a focus on drug sequencing and 'retreatment' approaches in the era of novel agents. Leukemia 2012; 26: 73-85. Figure 1 Figure 1. Disclosures Lal: Optum: Employment. Chastek:Optum: Employment. Blauer-Peterson:Optum: Employment. Maiese:Janssen Scientific Affairs, LLC: Employment.

Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

2019 ◽  
Vol 21 (10) ◽  
pp. 718-724 ◽  
Author(s):  
Wen-Cong Ruan ◽  
Yue-Ping Che ◽  
Li Ding ◽  
Hai-Feng Li
Keyword(s):  
Colorectal Cancer ◽  
Adverse Event ◽  
Metastatic Colorectal Cancer ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Clinical Prognosis ◽  
Line Therapy ◽  
Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2949-2951 ◽  
Author(s):  
Giovanni Palladini ◽  
Vittorio Perfetti ◽  
Stefano Perlini ◽  
Laura Obici ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Symptomatic Bradycardia ◽  
Intermediate Dose

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.

Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 51-51
Author(s):  
Xiaoyun Pan ◽  
Lincy S. Lal ◽  
John White ◽  
Seyed Hamidreza Mahmoudpour ◽  
Christian Valencia
Keyword(s):  
Cervical Cancer ◽  
Economic Burden ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Duration Of Treatment ◽  
Second Line Therapy ◽  
Treatment Regimens ◽  
Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer.

1995 ◽  
Vol 13 (11) ◽  
pp. 2722-2730 ◽  
Author(s):  
B L Weber ◽  
C Vogel ◽  
S Jones ◽  
H Harvey ◽  
L Hutchins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Breast ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy

PURPOSE We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease.

Salvage Therapies in Patients with High-Risk Relapse After Fludarabine, Cyclophosphamide, Rituximab (FCR) for Chronic Lymphocytic Leukemia: The French CLL Intergroup Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1796-1796
Author(s):  
Luc-Matthieu Fornecker ◽  
Therese Aurran-Schleinitz ◽  
Anne-Sophie Michallet ◽  
Bruno Cazin ◽  
Jehan Dupuis ◽  
...  
Keyword(s):  
High Risk ◽  
Second Line ◽  
Complex Karyotype ◽  
First Line ◽  
Second Line Therapy ◽  
High Risk Patients ◽  
First Line Therapy ◽  
Line Therapy ◽  
Ultra High Risk ◽  
Risk Patients

Abstract Abstract 1796 Introduction: FCR chemoimmunotherapy is recommended as first line therapy for fit cll patients. Since the 2007 EBMT guidelines based on the previously published trials using FCR, the definition of high risk CLL has evolved, to include biologic parameters (TP53 disruption by deletion/mutation, high b2-microglobulin level, IgVH unmutated, complex karyotype), refractoriness (progression during fluda-based regimen or within 6mo of completion), and also remission duration (high risk if PFS after FCR <24mo, ultra-high risk if TTNT <24–36mo with TP53 del/mut). However, few data are available regarding the characteristiscs, response rate and outcome of CLL patients treated in second line after FCR first line. Patients and methods: In this multicentric retrospective study, we collected data from 117 patients who relapsed after FCR first line therapy and received second-line therapy (according to NCI2008 guidelines). Results: At the time of initial FCR therapy: patients characteristics were as follows: Binet B/C 87.2%, unmutated IgVH 52.2%, del11q 25.6% (n=30/81 with FISH available), del17p 6.8% (n=8/87 with FISH available), bulk>5cm 22%, complex karyotype 21% (n=12/57 with karyotype available). FCR yielded 93% ORR, with 66% clinical CR, 27% PR, and 7% failed to respond. Median PFS and TTNT were 27mo and 32.5mo, respectively. At the time of relapse: patients characteristics were as follows: del11q 16.4% (n=19/65 with FISH available), del17p 19% (n=22/77), bulk>5cm 26%, complex karyotype 44% (n=24/54 with karyotype available). According to FCR remission duration, 11.1% of patients were considered as truly FCR-refractory, 47% had PFS<24mo, 34.2% had TTNT<24mo. TTNT<24mo after FCR was correlated to age>65y, del17p (20% vs 0%) and complex karyotype (38% vs11%), but not with gender, IgVH status, del11q, or bulk>5cm. Based on FCR-refractoriness, or TTNT<24mo and/or del17p, 53 patients were considered as ultra-high risk (45.3%). Various regimen were used for second-line treatment after FCR: R-bendamustine (n=47, 40.2%), alemtuzumab-based therapy (single agent or with chemo/dexa, n=22, 18.8%), R-CHOP (n=15, 12.8%), FCR (n=14, 12%), and other miscellaneous regimens (as follows: R-alkylator (n=6, 5.1%), R-DHAP (n=4, 3.4%), R-methylprednisolone (n=3, 2.6%), or investigational drugs (n=6, 5.1%)). Thus, 74.3% of patients received a second course including rituximab-based chemotherapy. Overall response rate was 78.4%, with 13.8% clinical CR, 64.6% PR, and 21.6% failure/stable disease. 14 pts (12%) underwent stem cell transplantations, 8 had maintenance therapy ongoing (ofatumumab, alemtuzumab, or lenalidomide). With regards to factors defining high-risk relapse, distribution of salvage therapies was as follows: As expected, a second course of FCR was seldom used in high-risk patients. Among ultra-high risk patients, 30.3% received R-benda, 11.3% Alem-based Rx, 32% R-CHOP and 18% the miscellaneous regimens described above. After second-line therapy, median PFS was 12 months, median TTNT was 14mo, and median OS was 36mo (20 deaths). On univariate analysis, complex karyotype (p=0.04) but not del17p (p=0.1), PFS<24mo (p=0.028) and TTNT<24mo (p=0.04) correlated with OS. Regarding treatment, OS was significantly improved in R-bendamustine-treated patients, as compared to alem-based or CHOP regimen (p=0.01). Most importantly, patients who received an allogeneic transplant benefited from significantly prolonged OS (at 4y, 70% vs 40%, p=0.03). Of note, only one patient treated with R-benda received allotransplant. Conclusions: This study shows that there are no consensus for second line therapy after FCR. Second line trials after FCR therapy are warranted. Definition of high-risk subsets of patients at relapse after FCR is of upmost importance in the management of CLL, to compare second-line strategies. Our data suggest that R-bendamustine is an efficient regimen even in high-risk patients (complex karyotype, PFS<24mo, TTNT<24mo). These data are important since this immunochemotherapy is now used as the backbone for combination with new compounds (ibrutinib, GS1101, GDC-199). Disclosures: Aurran-Schleinitz: Roche: Honoraria. Leblond:Roche: Advisory Board Other, Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Janssen-Cilag: Honoraria.

Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 641-641
Author(s):  
Kiyoshi Ishigure ◽  
Goro Nakayama ◽  
Keisuke Uehara ◽  
Hiroyuki Yokoyama ◽  
Akiharu Ishiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bleeding Event ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
To Receive

641 Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients. Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety. Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy. Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.

Determinants of first-line treatment selection in advanced pancreatic ductal adenocarcinoma (PDAC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 468-468
Author(s):  
Hui-Li Wong ◽  
Ying Wang ◽  
Yaling Yin ◽  
Hagen F. Kennecke ◽  
Winson Y. Cheung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Locally Advanced ◽  
Treatment Selection ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
The Impact ◽  
First Line Treatment

468 Background: Chemotherapy options currently available for the first-line treatment of advanced PDAC include FOLFIRINOX (FX), gemcitabine with nab-paclitaxel (GP) and single agent gemcitabine (Gem). GP was introduced most recently and funded for clinical use in British Columbia (BC) in September 2014. In this retrospective analysis, we explore the impact of GP availability on first-line treatment selection and overall survival (OS) in advanced PDAC. Methods: The BC Cancer Agency provincial pharmacy database was used to identify patients (pts) who started FX, GP or Gem between January and August 2014 (pre-GP) or January and August 2015 (post-GP). Pts were eligible for inclusion if they received at least one cycle of first-line therapy for locally advanced or metastatic PDAC. Clinical data were extracted from electronic medical records. OS was defined as time from diagnosis of advanced PDAC to death and compared by treatment era, adjusting for age, ECOG, comorbidities, disease extent and baseline CA19-9. Results: 286 pts fulfilled eligibility criteria: 88 (31%) with locally advanced and 198 (69%) with metastatic disease. 131 and 155 pts were treated in the pre- and post-GP eras respectively. Prior to GP approval, 44% and 49% of pts received Gem and FX; this decreased to 21% and 33% after GP funding, with 46% of pts receiving GP in the latter period. Nine (7%) pts received GP in the pre-GP era, either through self-pay or addition of nab-paclitaxel after approval. There were no significant differences in pt characteristics across both eras. 46% of pts who received GP post approval had ECOG ≥ 2. The proportion of pts receiving second-line therapy was lower in the post-GP era (22% vs. 38%). Median OS in the post-GP era was 8.1 vs. 10.1 months in the pre-GP era; adjusted HR 1.28 (95% CI 0.96–1.71). Pts with ECOG ≥ 2 who received GP had a median OS of 6.5 months. Conclusions: After GP was funded, it became the preferred first-line regimen for advanced PDAC. Its more frequent use instead of FX did not appear to compromise overall survival even though a substantial proportion of pts were ECOG ≥ 2 and few pts received second-line therapy.

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