scholarly journals Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma: Phase II Results From the Randomized, Placebo-Controlled LUME-Meso Trial

2017 ◽  
Vol 35 (31) ◽  
pp. 3591-3600 ◽  
Author(s):  
Federica Grosso ◽  
Nicola Steele ◽  
Silvia Novello ◽  
Anna K. Nowak ◽  
Sanjay Popat ◽  
...  
Keyword(s):  
Overall Survival ◽  
Placebo Group ◽  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Double Blind

Purpose LUME-Meso is a phase II/III randomized, double-blind trial designed to assess efficacy and safety of nintedanib plus chemotherapy as first-line treatment of malignant pleural mesothelioma (MPM). Phase II results are reported here. Patients and Methods Chemotherapy-naïve patients with unresectable, nonsarcomatoid MPM (Eastern Cooperative Oncology Group performance status 0 to 1), stratified by histology (epithelioid or biphasic), were randomly assigned in a 1:1 ratio to up to six cycles of pemetrexed and cisplatin plus nintedanib (200 mg twice daily) or placebo followed by nintedanib plus placebo monotherapy until progression. The primary end point was progression-free survival (PFS). Results Eighty-seven patients were randomly assigned. The median number of pemetrexed and cisplatin cycles was six; the median treatment duration for nintedanib was 7.8 months and 5.3 months for placebo. Primary PFS favored nintedanib (hazard ratio [HR], 0.56; 95% CI, 0.34 to 0.91; P = .017), which was confirmed in updated PFS analyses (HR, 0.54; 95% CI, 0.33 to 0.87; P = .010). A trend toward improved overall survival also favored nintedanib (HR, 0.77; 95% CI, 0.46 to 1.29; P = .319). Benefit was evident in epithelioid histology, with a median overall survival gain of 5.4 months (HR, 0.70; 95% CI, 0.40 to 1.21; P = .197; median [nintedanib v placebo], 20.6 months v 15.2 months) and median PFS gain of 4.0 months (HR, 0.49; 95% CI, 0.30 to 0.82; P = .006; median [nintedanib v placebo], 9.7 v 5.7 months). Neutropenia was the most frequent grade ≥ 3 adverse event (AE; nintedanib 43.2% v placebo 12.2%); rates of febrile neutropenia were low (4.5% in nintedanib group v 0% in placebo group). AEs leading to discontinuation were reported in 6.8% of those receiving nintedanib versus 17.1% of those in the placebo group. Conclusion Addition of nintedanib to pemetrexed plus cisplatin resulted in PFS improvement. AEs were manageable. The clinical benefit was evident in patients with epithelioid histology. The confirmatory phase III part of the study is ongoing.

GEM20110714: Final overall survival results of the phase III study of first-line gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6521-6521
Author(s):  
Shaodong Hong ◽  
Yan Huang ◽  
Yunpeng Yang ◽  
Gengsheng Yu ◽  
Jun Jia ◽  
...  
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Group Performance ◽  
Performance Status ◽  
Randomized Study ◽  
Eastern Cooperative Oncology Group ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Study

6521 Background: GEM20110714, the first randomized, phase III study (NCT01528618) of systemic chemotherapy in recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC), reported significant reduction of disease progression with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio [HR], 0.55; 95% CI, 0·44–0·68; P < .001). This study establishes GP as the standard-of-care for first-line treatment of R/M NPC. We present the final overall survival (OS) analysis here. Methods: In this multicenter, open-label study conducted in China, patients who had an Eastern Cooperative Oncology Group performance status of 0 or 1 and R/M NPC were randomly assigned (1:1) to receive up to six cycles of either GP or FP once every 3 weeks. The primary endpoint was PFS, which has been previously reported; OS was a secondary endpoint. The final OS analysis was conducted with the data cutoff date of December 17, 2019. Results: After a median follow-up time of 64.4 months (95% CI, 61.1-67.6), 148 (81.8%) and 165 (91.2%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.723 (95% CI, 0.578 to 0.904; two-sided P = .004). The median OS was 22.1 months with GP versus 18.6 months with FP. The OS probabilities at 1, 3, and 5 years were 79.9% vs. 71.8%, 31.0% vs. 20.4%, and 18.5% vs. 7.6%, respectively. Un-predefined subgroup analyses based on baseline characteristics were consistent with the primary OS analysis. Postdiscontinuation systemic therapy use was similar: GP, 52%; FP, 57%. No new safety signals emerged. Conclusions: In patients with R/M NPC, GP is the first regimen to show significant improvement in OS in a phase III randomized study compared with a traditional chemotherapy regimen (i.e. FP). GP should be considered the standard treatment option for these patients. Clinical trial information: NCT01528618 .

Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients With Cancer

2017 ◽  
Vol 35 (17) ◽  
pp. 1921-1928 ◽  
Author(s):  
Nobuyuki Katakami ◽  
Koji Oda ◽  
Katsunori Tauchi ◽  
Ken Nakata ◽  
Katsunori Shinozaki ◽  
...  
Keyword(s):  
Group Performance ◽  
Day Treatment ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Controlled Study ◽  
Frequency Change ◽  
Double Blind ◽  
Patients With Cancer ◽  
End Point

Purpose This randomized, double-blind, multicenter study aimed to determine the dose of naldemedine, a peripherally-acting μ-opioid receptor antagonist, for future trials by comparing the efficacy and safety of three doses of naldemedine versus placebo in patients with cancer and opioid-induced constipation. Methods Patients ≥ 18 years old with cancer, an Eastern Cooperative Oncology Group performance status ≤ 2, who had been receiving a stable regimen of opioid analgesics for ≥ 2 weeks, had at least one constipation symptom despite laxative use, and no more than five spontaneous bowel movements (SBMs) during the past 14 days, were randomly assigned (1:1:1:1) to oral, once-daily naldemedine 0.1, 0.2, or 0.4 mg, or placebo, for 14 days. The primary end point was change in SBM frequency per week from baseline during the treatment period. Secondary end points included SBM responder rates, change from baseline in the frequency of SBM without straining, and complete SBM. Safety was also assessed. Results Of 227 patients who were randomly assigned, 225 were assessed for efficacy (naldemedine 0.1 mg, n = 55; 0.2 mg, n = 58; 0.4 mg, n = 56; placebo, n = 56) and 226 for safety. Change in SBM frequency (primary end point) was higher with all naldemedine doses versus placebo ( P < .05 for all comparisons), as were SBM responder rates and change in complete SBM frequency. Change in SBM frequency without straining was significantly improved with naldemedine 0.2 and 0.4 (but not 0.1) mg versus placebo (at least P < .05). Treatment-emergent adverse events were more common with naldemedine (0.1 mg: 66.1%; 0.2 mg: 67.2%; 0.4 mg: 78.6%) than placebo (51.8%); the most common treatment-emergent adverse event was diarrhea. Conclusion Fourteen-day treatment with naldemedine significantly improved opioid-induced constipation in patients with cancer and was generally well tolerated. Naldemedine 0.2 mg was selected for phase III studies.

scholarly journals Phase II Study of Sorafenib in Combination With Docetaxel and Cisplatin in the Treatment of Metastatic or Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: ECOG 5203

2010 ◽  
Vol 28 (18) ◽  
pp. 2947-2951 ◽  
Author(s):  
Weijing Sun ◽  
Mark Powell ◽  
Peter J. O'Dwyer ◽  
Paul Catalano ◽  
Rafat H. Ansari ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Study ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Free Survival

Purpose The combination of sorafenib with chemotherapy is well-tolerated and is associated with encouraging response rates in several malignances. Both docetaxel and cisplatin are active in gastric cancer. A phase II study was conducted to determine the efficacy and toxicity of combined sorafenib, docetaxel, and cisplatin in patients with metastatic or advanced adenocarcinoma of stomach or gastroesophageal junction (GEJ). Patients and Methods Forty-four chemotherapy-naïve patients with Eastern Cooperative Oncology Group performance status 0 or 1, of whom 80% had metastatic disease and two thirds had poorly differentiated gastric or GEJ adenocarcinoma, were enrolled. The treatment regimen was sorafenib 400 mg orally twice a day for 21 days, docetaxel 75 mg/m2 intravenously on day 1, and cisplatin 75 mg/m2 intravenously on day 1, repeated every 21 days. The primary end point was response rate to the combination. Toxicity, overall survival, and progression-free survival were assessed as secondary end points. Results Eighteen of the 44 eligible and treated patients showed partial responses (41%; 90% CI, 28% to 54%). The median progression-free survival was 5.8 months (90% CI, 5.4 to 7.4 months). The median overall survival was 13.6 months (90% CI, 8.6 to 16.1 month). The major toxicity of this regimen was neutropenia, which reached grade 3 to 4 in 64% of patients. One patient experienced hemorrhage at the tumor site. Conclusion The combination of sorafenib, docetaxel, and cisplatin has an encouraging efficacy profile with tolerable toxicity. Additional studies of sorafenib with chemotherapy are warranted in gastric cancer.

Regorafenib (REG) in patients with hepatocellular carcinoma (HCC) progressing following sorafenib: An ongoing randomized, double-blind, phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS4163-TPS4163
Author(s):  
Ann-Lii Cheng ◽  
Richard S. Finn ◽  
Masatoshi Kudo ◽  
Josep M. Llovet ◽  
Shukui Qin ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Open Label ◽  
Double Blind ◽  
Sorafenib Treatment ◽  
Phase Iii Trial ◽  
Ecog Ps

TPS4163 Background: Sorafenib is the accepted first-line systemic therapy for HCC, but no standard option is available for patients with tumor progression following sorafenib. An open-label phase II study suggested that REG, a multikinase inhibitor, had an acceptable safety profile and showed evidence of antitumor activity in patients with progressive HCC (Bolondi et al. Eur J Cancer 2011; 47 [Suppl 1]: abstract 6.576): disease control was achieved in 26/36 patients (72%) and median time to progression (TTP) was 4.3 months; median overall survival (OS) was 13.8 months. On the basis of these promising data, a phase III trial was designed. Methods: This randomized, double-blind, placebo (PBO)-controlled, multinational study (ClinicalTrials.gov identifier NCT01774344) will assess the efficacy and tolerability of REG vs PBO in patients with HCC that has progressed following sorafenib treatment (target n=530). Inclusion criteria include Barcelona Clinic Liver Cancer stage B or C disease, Child–Pugh A liver function, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. Patients who discontinued sorafenib ≥8 weeks before study entry or who received other previous systemic therapy for HCC will be excluded. Patients will be randomized in a 2:1 ratio to receive REG 160 mg or matching PBO OD for weeks 1–3 of each 4-week cycle; all patients will also receive best supportive care. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Doses of study drug may be delayed or reduced to manage clinically significant drug-related toxicities. The primary endpoint is OS; secondary endpoints are TTP, progression-free survival, tumor response, and safety. Analysis will be according to randomized group, stratified by geographic region (Asia vs rest of world), ECOG PS (0 vs 1), alfa-fetoprotein level (<400 vs ≥400 ng/ml), extrahepatic disease (yes vs no), and macrovascular invasion (yes vs no). In addition, blood, plasma, and archival tissue will be assessed for pharmacokinetic and biomarker analyses, and health-related quality of life and health utility will be measured. Clinical trial information: NCT01774344.

Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4134-TPS4134 ◽  
Author(s):  
T.R. Jeffry Evans ◽  
Eric Van Cutsem ◽  
Malcolm J. Moore ◽  
Joseph D. Purvis ◽  
Lewis C. Strauss ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Migration And Invasion ◽  
Double Blind

TPS4134 Background: Dasatinib, a potent oral BCR-ABL and SRC family kinase (SFK) inhibitor, is approved for first- and second-line therapy of Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML) in pts with newly diagnosed CML or CML resistant/intolerant to prior therapy. SRC expression and activity is upregulated in PaCa and correlates with reduced survival in resected high-grade PaCa (Morton, Gastroenterology 2010) and resistance to Gem, a PaCa standard of care (Duxbury, J Am Coll Surg 2004). In preclinical PaCa studies, inhibition of SFKs with dasatinib reduces tumor cell proliferation, migration, and invasion; increases apoptosis; sensitizes cells to Gem; and inhibits development of metastases in vivo either alone or in combination with Gem (Duxbury, Clin Cancer Res 2004; Duxbury, J Am Coll Surg 2004; Nagaraj, Mol Cancer Ther 2010; Morton, op cit). Phase I clinical studies of dasatinib and Gem therapy in PaCa have demonstrated feasibility and suggested efficacy of the combination (Uronis, ASCO 2009, abstract e15506). Methods: This double-blind phase II study tests whether addition of dasatinib to Gem is tolerable and improves efficacy in pts with histologically/cytologically confirmed unresectable locally advanced nonmetastatic PaCa. Eligible pts, aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and adequate organ function, are randomized 1:1 to Gem 1000 mg/m2 IV once weekly (Weeks 1–3 of a 4-week cycle) plus either dasatinib 100 mg once daily or matched placebo. Pts are treated until progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoint is OS, and secondary endpoints are progression-free survival and safety. Exploratory endpoints include freedom from distant metastases, measures of pain and fatigue, overall response rate, and carbohydrate antigen 19-9. Final study analysis will be conducted after 135 deaths; all pts will be followed for survival. To date, 23/200 pts have enrolled; estimated primary completion date is March 2013. ClinicalTrials.gov identifier: NCT01395017.

scholarly journals Meta-Analysis of Survival and Development of a Prognostic Nomogram for Malignant Pleural Mesothelioma Treated with Systemic Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2186
Author(s):  
Rupesh Kotecha ◽  
Raees Tonse ◽  
Muni Rubens ◽  
Haley Appel ◽  
Federico Albrecht ◽  
...  
Keyword(s):  
Phase Ii ◽  
Malignant Pleural Mesothelioma ◽  
Systemic Chemotherapy ◽  
Meta Analysis ◽  
Performance Status ◽  
Locally Advanced ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Prognostic Variables ◽  
Phase Ii Studies

(1) Purpose: Malignant pleural mesothelioma (MPM) is a rare cancer with an aggressive course. For patients who are medically inoperable or surgically unresectable, multi-agent systemic chemotherapy remains an accepted standard-of-care. The purpose of this meta-analysis is to provide baseline summative survival estimates as well as evaluate the influence of prognostic variables to provide comparative estimates for future trial designs. (2) Methods: Using PRISMA guidelines, a systematic review and meta-analysis was performed of MPM studies published from 2002–2019 obtained from the Medline database evaluating systemic therapy combinations for locally advanced or metastatic disease. Weighted random effects models were used to calculate survival estimates. The influence of proportions of known prognostic factors on overall survival (OS) were evaluated in the creation of a prognostic nomogram to estimate survival. The performance of this model was evaluated against data generated from one positive phase II study and two positive randomized trials. (3) Results: Twenty-four phase II studies and five phase III trials met the eligibility criteria; 2534 patients were treated on the included clinical studies. Ten trials included a platinum-pemetrexed-based treatment regimen, resulting in a pooled estimate of progression-free survival (PFS) of 6.7 months (95% CI: 6.2–7.2 months) and OS of 14.2 months (95% CI: 12.7–15.9 months). Fifteen experimental chemotherapy regimens have been tested in phase II or III studies, with a pooled median survival estimate of 13.5 months (95% CI: 12.6–14.6 months). Meta-regression analysis was used to estimate OS with platinum-pemetrexed using a variety of features, such as pathology (biphasic vs. epithelioid), disease extent (locally advanced vs. metastatic), ECOG performance status, age, and gender. The nomogram-predicted estimates and corresponding 95% CIs performed well when applied to recent randomized studies. (4) Conclusions: Given the rarity of MPM and the aggressive nature of the disease, innovative clinical trial designs with significantly greater randomization to experimental regimens can be performed using robust survival estimates from prior studies. This study provides baseline comparative values and also allows for accounting for differing proportions of known prognostic variables.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine

2017 ◽  
Vol 35 (30) ◽  
pp. 3433-3439 ◽  
Author(s):  
George D. Demetri ◽  
Patrick Schöffski ◽  
Giovanni Grignani ◽  
Jean-Yves Blay ◽  
Robert G. Maki ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eribulin Mesylate ◽  
Systemic Treatments ◽  
Phase Iii Study

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

scholarly journals Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation

2020 ◽  
Vol 38 (13) ◽  
pp. 1378-1388 ◽  
Author(s):  
Eileen M. O’Reilly ◽  
Jonathan W. Lee ◽  
Mark Zalupski ◽  
Marinela Capanu ◽  
Jennifer Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Open Label ◽  
Free Survival ◽  
Palb2 Mutation

PURPOSE Five percent to 9% of pancreatic ductal adenocarcinomas (PDACs) develop in patients with a germline BRCA1/2 or PALB2 (g BRCA/PALB2+) mutation. Phase IB data from a trial that used cisplatin, gemcitabine, and veliparib treatment demonstrated a high response rate (RR), disease control rate (DCR), and overall survival (OS) in this population. We designed an open-label, randomized, multicenter, two-arm phase II trial to investigate cisplatin and gemcitabine with or without veliparib in g BRCA/PALB2+ PDAC. PATIENTS AND METHODS Eligible patients had untreated g BRCA/PALB2+ PDAC with measurable stage III to IV disease and Eastern Cooperative Oncology Group performance status of 0 to 1. Treatment for patients in arm A consisted of cisplatin 25 mg/m2 and gemcitabine 600 mg/m2 intravenously on days 3 and 10; treatment for patients in arm B was the same as that for patients in arm A, and arm A also received veliparib 80 mg orally twice per day on days 1 to 12 cycled every 3 weeks. The primary end point was RRs of arm A and arm B evaluated separately using a Simon two-stage design. Secondary end points were progression-free survival, DCR, OS, safety, and correlative analyses. RESULTS Fifty patients were evaluated by modified intention-to-treat analysis. The RR for arm A was 74.1% and 65.2% for arm B ( P = .55); both arms exceeded the prespecified activity threshold. DCR was 100% for arm A and 78.3% for arm B ( P = .02). Median progression-free survival was 10.1 months for arm A (95% CI, 6.7 to 11.5 months) and 9.7 months for arm B (95% CI, 4.2 to 13.6 months; P = .73). Median OS for arm A was 15.5 months (95% CI, 12.2 to 24.3 months) and 16.4 months for arm B (95% CI, 11.7 to 23.4 months; P = .6). Two-year OS rate for the entire cohort was 30.6% (95% CI, 17.8% to 44.4%), and 3-year OS rate was 17.8% (95% CI, 8.1% to 30.7%). Grade 3 to 4 hematologic toxicities for arm A versus arm B were 13 (48%) versus seven (30%) for neutropenia, 15 (55%) versus two (9%) for thrombocytopenia, and 14 (52%) versus eight (35%) for anemia. CONCLUSION Cisplatin and gemcitabine is an effective regimen in advanced g BRCA/PALB2+ PDAC. Concurrent veliparib did not improve RR. These data establish cisplatin and gemcitabine as a standard approach in g BRCA/ PALB2+ PDAC.

Prognostic factors of ado-trastuzumab emtansine treatment in patients with metastatic HER-2 positive breast cancer

2020 ◽  
pp. 107815522092408 ◽  
Author(s):  
Deniz Tataroglu Ozyukseler ◽  
Mustafa Basak ◽  
Seval Ay ◽  
Aygül Koseoglu ◽  
Serdar Arıcı ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Trastuzumab Emtansine ◽  
Oncology Group ◽  
Cancer Antigen ◽  
Free Survival

Background Ado-trastuzumab emtansine is an antibody-drug conjugate that combines the cytotoxic activity of emtansine with human epidermal growth factor receptor 2-targeted antitumor features of trastuzumab. Objective We conducted a study of metastatic breast cancer patients treated with trastuzumab emtansine. By evaluating progression-free survival, overall survival, and response rates, we aimed to find prognostic factors of trastuzumab emtansine treatment. Methods Our study is a single-center, retrospective, observational study. We have clinical data from 78 patients treated with trastuzumab emtansine for metastatic breast cancer, from May 2016 through May 2019, at Kartal Dr Lutfi Kirdar Education and Research Hospital, Medical Oncology Department. Our objective is to assess the survival and response rates in trastuzumab emtansine-treated individuals and the factors associated with survival. The factors we analyzed were cancer antigen 15-3 sensitivity, Eastern Cooperative Oncology Group-Performance Status, presence or absence of visceral metastases, presence or absence of cranial metastases, and treatment-associated thrombocytopenia. Results Among 78 patients, median progression-free survival was 7.8 months, and overall survival was 21.1 months. Twenty of the patients had an objective tumor response. The results showed that trastuzumab emtansine was tolerable with a manageable safety profile and consistent with the results of the previous literature. Mostly seen adverse events were anemia, thrombocytopenia, fatigue, and increased levels of alkaline phosphatase. Patients with Eastern Cooperative Oncology Group-Performance Status = 2 had worse progression-free survival and overall survival compared to ones with Eastern Cooperative Oncology Group-Performance Status < 2; progression-free survival and overall survival are worse in cancer antigen 15-3-sensitive breast cancer patients. According to our findings, treatment-associated thrombocytopenia was a significant prognostic factor for survival. Patients with thrombocytopenia had 12 months progression-free survival, whereas patients without thrombocytopenia had only 4.1 months progression-free survival. In like manner, overall survival was much better in the thrombocytopenia-experienced patients as 29.5 versus 11.8 months. Conclusions Trastuzumab emtansine prolongs progression-free survival and overall survival with a manageable safety profile. Thrombocytopenia, Eastern Cooperative Oncology Group-Performance Status, and cancer antigen 15-3 are correlated with progression-free survival and/or overall survival.

Optimizing Treatment for Elderly Patients With Newly Diagnosed Multiple Myeloma: A Personalized Approach

2016 ◽  
Vol 34 (30) ◽  
pp. 3600-3604 ◽  
Author(s):  
Alessandra Larocca ◽  
Antonio Palumbo
Keyword(s):  
Multiple Myeloma ◽  
Group Performance ◽  
Performance Status ◽  
Relevant Literature ◽  
Eastern Cooperative Oncology Group ◽  
Staging System ◽  
Phase Iii ◽  
Bone Lesions ◽  
Best Response ◽  
Personalized Approach

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. An 84-year-old woman presented with bone pain and lytic bone lesions in April 2010. Diagnosis of multiple myeloma was based on the presence of an immunoglobulin G lambda serum M protein (4,784 mg/dL) and confirmed by the findings of bone marrow plasma cell infiltration, with t(11;14) chromosomal abnormality detected by fluorescence in situ hybridization analysis. The patient’s medical history was significant for hypertension; she had an Eastern Cooperative Oncology Group performance status of 1, International Staging System (ISS) stage of 1, and Durie–Salmon stage of IIIA. In May 2010, the patient was enrolled in a randomized phase III trial comparing different lenalidomide-based treatments and received induction with lenalidomide plus dexamethasone (nine cycles) followed by lenalidomide maintenance. The patient started treatment with lenalidomide 25 mg per day for 21 days and reduced-dose dexamethasone 20 mg per week per protocol because of age. Induction was well tolerated; no relevant complications occurred, except for grade 1 fatigue and grade 1 diarrhea. Best response was partial response. In March 2011, she started maintenance with lenalidomide 10 mg per day. A dose reduction of lenalidomide 5 mg per day was required because of grade 2 diarrhea. In July 2015, the patient experienced relapse, with painful collapse of L3 vertebral body.

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