Differential progression-free survival (PFS) to erlotinib according to EGFR exon 19 deletion type in non-small cell lung cancer (NSCLC) patients (p) in the EURTAC study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
Enric Carcereny Costa ◽  
Miquel Taron ◽  
Cristina Queralt ◽  
Itziar de Aguirre ◽  
Laia Capdevila ◽  
...  
Keyword(s):  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
In Vitro Sensitivity ◽  
Duration Of Response ◽  
Exon 19 Deletion ◽  
Nsclc Patients ◽  
To Receive ◽  
Exon 19

7540 Background: Different exon 19 deletion types have shown different in vitro sensitivity to erlotinib, with the lower IC50 for deletion E746_A750 (ELREA) (Yuza et al. Cancer Biol Ther 2007). This information prompted us to examine outcome according to type of exon 19 deletion in the EURTAC study. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Progression-free survival (PFS) was 9.7 months (m) vs 5.2 m, respectively (P<0.0001). Exon 19 deletions were divided into two groups: ELREA vs non-ELREA deletions. Results: Exon 19 deletions were present in 57 p in the erlotinib arm and in 58 p in the chemotherapy arm. ELREA deletions were found in 41 p (71.9%) in the erlotinib arm and in 38 p (65.5%) in the chemotherapy arm. Non-ELREA deletions were found in 16 p in the erlotinib arm and in 20 p in the chemotherapy arm. There were no differences in p characteristics between treatment arms according to type of deletion. PFS for p with ELREA deletions was 9.4 m in the erlotinib arm and 4.6 in the chemotherapy arm (HR, 0.36; P=0.0004). PFS for p with non-ELREA deletions was not reached in p in the erlotinib arm and was 5.3 m for p in the chemotherapy arm (HR, 0.17; P=0.001). The multivariate analysis identified erlotinib arm (P<0.001) and non-ELREA deletions (P=0.001) as independent markers of longer PFS. Overall survival (OS) for p with ELREA deletions was 17 m in the erlotinib arm and 18.4 in the chemotherapy arm (P=0.575). OS for p with non-ELREA deletions was not reached in the erlotinib arm and 19.5 m in the chemotherapy arm (P=0.216). Response rate (RR) for p with ELREA deletions was 53.6% in the erlotinib arm vs 15.7% in the chemotherapy arm (P=0.004). RR for p with non-ELREA deletions was 68.7% in the erlotinib arm vs 10% in the chemotherapy arm (P=0.001). Conclusions: To date, no biological reason has been identified that can explain the greater sensitivity to erlotinib in p with non-ELREA exon 19 deletions. Our findings indicate the need to define the type of deletion prior to treatment since this information can be helpful in predicting the duration of response.

Skin toxicity associated with outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) with EGFR mutations in the EURTAC study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7542-7542
Author(s):  
Cristina Buges ◽  
Alex Martinez Marti ◽  
Rafael Rosell ◽  
Alain Vergnenegre ◽  
Filippo De Marinis ◽  
...  
Keyword(s):  
Skin Rash ◽  
Smoking Status ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Egfr Mutations ◽  
Free Survival ◽  
Nsclc Patients ◽  
First Time ◽  
To Receive ◽  
Exon 19

7542 Background: Rash is reported in 75% of p treated with erlotinib and has been associated with improved overall and progression-free survival (PFS) in unselected p although not specifically in p with EGFR mutations. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Overall PFS was 9.7 months (m) vs 5.2 m, respectively (P<0.0001). Rash was defined according to NCI CTC v3.0 and dichotomized by grades 0-1 vs 2+. Grade 2 is macular or popular eruption or erythema with pruritus or other associated symptoms, localized desquamation or other lesions covering <50% of body surface area. We examined outcome in the erlotinib arm according to rash grade. Results: 16 p in the erlotinib arm had no rash (grade 0), 30 had grade 1, and 40 had grade 2+. 80% of cases of rash grade 2+ occurred in p with exon 19 deletions, while only 20% were in p with L858R mutations (P=0.039). There were no differences in rash grade according to sex, age or smoking status. PFS was 11.2 m in p with rash grade 2+ and 8.4 m in p with grade 0-1 (HR, 0.52; P=0.018). There was no correlation between rash grade 0-1 vs 2+ and response or overall survival (OS). Interestingly, when p were divided into those with no rash (16 p) and those with grade 2+ (40 p), PFS was 11.2 m for p with grade 2+ vs 2.7 m for p with no rash (P=0.031), and OS was 24.9 m for p with grade 2+ vs 16.1 m for p with no rash (P=0.033). Conclusions: Although the biological reasons for the association of skin rash with better outcome to erlotinib have not been elucidated, this sub-analysis of the EURTAC trial has enabled us to confirm for the first time that skin rash – especially grade 2+ - can predict better outcome to erlotinib in p with EGFR mutations. In addition, the correlation between rash and type of EGFR mutation warrants further investigation.

Response to erlotinib and prognosis for patients with de novo epidermal growth factor receptor (EGFR) T790M mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8018-8018 ◽  
Author(s):  
Gregory J. Riely ◽  
Helena Alexandra Yu ◽  
Maria E. Arcila ◽  
Matthew David Hellmann ◽  
Marc Ladanyi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
De Novo ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
Egfr Tki ◽  
Egfr T790m ◽  
Exon 19

8018 Background: A secondary mutation in exon 20 of EGFR, T790M, is the most common cause of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR mutant lung cancers. De novo EGFR T790M mutations in TKI-naïve patients are rare when assessed by standard genotyping methods. The response to EGFR TKIs in patients with de novo EGFR T790M mutations is unknown. Methods: Patients with EGFRmutations were identified through routine testing, using PCR-based fragment length analysis, mass spectrometry-based genotyping (Sequenom), and Sanger sequencing. Clinical characteristics, progression free survival (PFS) from start of EGFR TKI and overall survival (OS) were obtained from the medical record. Results: From 2008-2012, we observed EGFR T790M in 21 tumors from 20 patients who had not previously been treated with an EGFR TKI representing <2% of all tumors with identified EGFR mutations. Two patients are included in reports from the Lung Cancer Mutation Consortium. The median age at lung cancer diagnosis was 57 (range 35-90). 55% presented with stage IV disease. 60% were women. 65% were never-smokers. In all cases, T790M occurred concurrently with another EGFR mutation, L858R (76%, 16/21) or exon 19 deletion (24%, 5/21). Compared to a contemporary cohort of 593 patients with EGFR mutations, in these patients with de novo EGFR T790M, L858R was more frequent than exon 19 deletion (p=0.003). Thirteen patients received erlotinib monotherapy as treatment for metastatic disease. Their response rate (CR+PR) was 9% (1/11, 95% Confidence Interval: 0-40%). SD was observed in 36% (4/11). The median progression-free survival was 3 months and the median overall survival was 16 months. Conclusions: De novo EGFR T790M mutations are rare and occur most commonly with EGFR L858R. Overall survival for patients with de novo EGFR T790 mutations is shorter than what is seen in patients with EGFR exon 19 deletions or L858R, and appears more similar to EGFR wild-type patients. Response rate to EGFR TKI in these patients is low. EGFR TKI therapy for patients with de novo EGFR T790M appears to have limited objective benefit and should be considered only after standard cytotoxic chemotherapy.

scholarly journals Efficacy of S-1 after pemetrexed in patients with non-small cell lung carcinoma: a retrospective multi-institutional analysis

2021 ◽  
Author(s):  
Shinnosuke Takemoto ◽  
Kazumasa Akagi ◽  
Sawana Ono ◽  
Hiromi Tomono ◽  
Noritaka Honda ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Small Cell Lung Carcinoma ◽  
Progression Free Survival ◽  
Small Cell Lung ◽  
Confidential Interval ◽  
Cell Lung Carcinoma ◽  
Free Survival ◽  
Time To Treatment Failure ◽  
Nsclc Patients

Abstract Background: This study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment. Methods: This retrospective study included patients with advanced (c-stage III or IV, UICC 7th) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at 6 hospitals in Japan. Primary endpoint: Overall response rate (ORR). Secondary endpoint: Disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS). Results: A total of 53 NSCLC patients met the criteria. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidential interval (CI): 0.00-10.1%). Median TTF, PFS, and OS were 65 days, 84 days, and 385 days, respectively. Conclusion: Although there were several limitations in this study, the ORR of S-1 after PEM in patients with non-SQ NSCLC was low compared to the historical control. It might be one of the choices to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

1998 ◽  
Vol 16 (8) ◽  
pp. 2739-2744 ◽  
Author(s):  
Y Bécouarn ◽  
M Ychou ◽  
M Ducreux ◽  
C Borel ◽  
F Bertheault-Cvitkovic ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Peripheral Sensory

PURPOSE To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1992 ◽  
Vol 10 (7) ◽  
pp. 1066-1073 ◽  
Author(s):  
P J Loehrer ◽  
L H Einhorn ◽  
P J Elson ◽  
E D Crawford ◽  
P Kuebler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Response Rate ◽  
Combined Therapy ◽  
Single Agent ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Urothelial Carcinoma ◽  
Advanced Urothelial Carcinoma ◽  
To Receive

PURPOSE A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

A randomized double-blind trial of carboplatin plus paclitaxel (CP) with daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo (PLA) in patients (pts) with previously untreated advanced non-small cell lung cancer (NSCLC):  NCIC Clinical Trials Group study BR29.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7511-7511 ◽  
Author(s):  
Scott Andrew Laurie ◽  
Benjamin J. Solomon ◽  
Lesley Seymour ◽  
Peter Michael Ellis ◽  
Glenwood D. Goss ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Vascular Endothelial ◽  
Double Blind ◽  
Free Survival ◽  
Endothelial Growth Factor ◽  
To Receive ◽  
Unacceptable Toxicity

7511 Background: In NCIC CTG study BR24, CED 30 mg/d + CP increased objective response rate (RR) and progression-free survival (PFS), but there were concerns regarding toxicity in some pts. BR29 tested a lower dose of CED 20 mg/d limiting accrual to pts without significant weight loss/hypoalbuminemia. Methods: Consenting, eligible adult pts with advanced incurable NSCLC of any histology were randomized to receive CED 20 mg/d or PLA with up to 6 cycles of C (AUC = 6) P (200 mg/m2); non-progressing pts continued CED/PLA after CP until progression, unacceptable toxicity or pt request. The primary endpoint was overall survival (OS). An interim analysis (IA) for PFS was planned after 170 events in the first 260 pts; the study would continue if the hazard ratio (HR) for PFS was < 0.7. Accrual continued until the required number of events was reached then held pending IA. Results: The trial was halted when the IA (n=260) revealed a HR for PFS of 0.89 (95% CI 0.66-1.20). A final analysis including all 306 randomized pts (median age 62, male 55%, PS 0 26%, PS 1 74%, adenocarcinoma 64%, squamous 13%, other histology 23%. RR was significantly higher with CED (52% vs 34 %, p = 0.001). For CED/PLA, respectively, median OS and PFS were 12.2/12.1 [HR: 0.95 (0.69-1.30, p=0.74)] and 5.5/5.5 months [HR: 0.91 (0.71-1.18, p=0.5)]. Grade >3 hypertension (15% vs 3%, p=0.0002), anorexia (7% vs 1%, p=0.02) and diarrhea (16% vs 1%, p<0.0001) were all significantly increased with CED; there were 2 deaths possibly-related to CED [1 each hemorrhage, leukoencephalopathy (prior radiation)]. Conclusions: Adding a lower dose of CED to CP increased RR and toxicity, but not PFS or OS.

Clinical implications of the T790M mutation in disease characteristics and treatment response in patients with EGFR-mutated NSCLC.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9031-9031
Author(s):  
Daria Gaut ◽  
Myung Shin Sim ◽  
Brian R. Wolf ◽  
Phillip A. Abarca ◽  
James M. Carroll ◽  
...  
Keyword(s):  
Medical Records ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Resistance Mutation ◽  
Progression Free Survival ◽  
First Line ◽  
T790m Mutation ◽  
Free Survival ◽  
Egfr Mutant ◽  
Nsclc Patients

9031 Background: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in epidermal growth factor receptor (EGFR)-mutant NSCLC patients. Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown about this resistance mechanism’s association with response to other therapies. Methods: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing in the process of screening for clinical trials involving third generation EGFR inhibitors. Medical records were retrospectively analyzed for demographic data, PFS, best response (BR) to previous therapies, and presence or absence of an acquired T790M mutation. Progression-free survival was estimated using the Kaplan-Meier method and compared across two groups using the log-ranked test followed by univariate and multivariate cox proportional hazard regression analysis. Response rates were compared using Fisher’s exact test. Results: Out of 102 patients who obtained a diagnostic biopsy, 73 patients had a T790M mutation. Patients who later developed a T790M mutation had a longer PFS on first-line TKI therapy (12.0 months in T790M+ vs. 8.0 months in T790M-, p = 0.038, HR 1.66, 95% CI 1.03-2.67), though there was no difference in response rate (75.5% in T790M+ vs 77.3% in T790M-, p = 1.00). T790M+ patients also had a longer PFS on initial chemotherapy treatment (5.0 months in T790M+ vs. 4.0 months in T790M-, p = 0.020, HR 1.97, 95% CI 1.11-3.49) and a higher response rate to chemotherapy (22.7% in T790M+ vs 0% in T790M-, p = 0.033). Median PFS was short (3.0 months) for patients treated with immunotherapy with no difference based on T790M mutation status (p = 0.33). Conclusions: Our study confirms that tumors expressing T790M have a more indolent progression of disease compared to their T790M negative counterparts when treated with both first-line TKI and cytotoxic chemotherapy. This data provides context for therapeutic decision making in EGFR-mutant NSCLC patients.

Randomized Multicenter Phase II Trial of Two Different Schedules of Capecitabine Plus Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer

2003 ◽  
Vol 21 (7) ◽  
pp. 1307-1312 ◽  
Author(s):  
Werner Scheithauer ◽  
Gabriela V. Kornek ◽  
Markus Raderer ◽  
Birgit Schüll ◽  
Katharina Schmid ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Progression Free Survival ◽  
Synergistic Activity ◽  
Free Survival ◽  
Multicenter Phase ◽  
To Receive

Purpose: Capecitabine and oxaliplatin, two new agents with potential synergistic activity, have demonstrated promising antitumor efficacy in advanced colorectal cancer (ACC). Preclinical and clinical evidence indicating that dose intensification of the oral fluorouracil prodrug might result in improved therapeutic results led us to the present randomized multicenter phase II study. Patients and Methods: Eighty-nine patients with bidimensionally measurable ACC previously untreated for metastatic disease were randomly allocated to receive oxaliplatin 130 mg/m2 day 1 plus capecitabine 2,000 mg/m2/d days 1 to 14 every 3 weeks (arm A) or to receive oxaliplatin 85 mg/m2 days 1 and 14 combined with capecitabine 3,500 mg/m2 days 1 to 7 and 14 to 21 every 4 weeks (arm B). In both treatment arms, chemotherapy was continued for a total of 6 months unless there was prior evidence of progression of disease. Results: Patients allocated to the high-dose capecitabine combination arm B had a higher radiologically confirmed response rate (54.5% v 42.2%) and a significantly longer median progression-free survival time than those allocated to control arm A (10.5 v 6.0 months; P = .0013). Median overall survival times cannot be calculated for either treatment arm at this point. Despite a 34% higher dose intensity of capecitabine in arm B, there was no difference in hematologic toxicity between treatment arms (neutropenia/thrombocytopenia: 60%/43% in arm B v 56%/33% in arm A). Similarly, the incidence rate and degree of nonhematologic adverse events were comparable: The most commonly encountered symptoms (all grades, arm A and arm B) included nausea/emesis (A: 58%; B: 62%), diarrhea (A: 44%; B: 31%), peripheral sensory neuropathy (A: 80%; B: 83%), and fatigue (A: 40%; B: 50%). Conclusion: Results of this study indicate that both combination regimens are feasible, tolerable, and clinically active. The dose-intensified bimonthly capecitabine arm, however, seems to be more effective in increasing both response rate and progression-free survival time.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

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