Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 204-204
Author(s):  
Keisho Chin ◽  
Ken Kato ◽  
Byoung Chul Cho ◽  
Masanobu Takahashi ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Subgroup Analysis ◽  
Survival Data ◽  
Special Interest ◽  
Safety Data ◽  
Phase Iii ◽  
Taxane Chemotherapy ◽  
Favorable Safety ◽  
Safety Signals

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.

Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 559-559 ◽  
Author(s):  
Martine J. Piccart-Gebhart ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
Howard A. Burris ◽  
Hope S. Rugo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitor ◽  
Postmenopausal Women ◽  
Survival Data ◽  
Treatment Options ◽  
Safety Data ◽  
Phase Iii ◽  
Double Blind ◽  
Once Daily

559 Background: Current treatment options for postmenopausal patients with estrogen-receptor–positive (ER+) breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) are limited. The BOLERO-2 trial supports the activity of everolimus (EVE; an oral mammalian target of rapamycin [mTOR] inhibitor) added to the steroidal aromatase inhibitor exemestane (EXE) to prolong progression-free survival (PFS) in this patient population. Long-term PFS and survival data are awaited. Methods: BOLERO-2 is a phase III double-blind, randomized, international trial comparing EVE (10 mg once daily) plus EXE (25 mg once daily) versus placebo (PBO) plus EXE in postmenopausal women with advanced ER+ BC progressing or recurring after NSAIs (letrozole or anastrozole). Patients were randomized (2:1) to EVE + EXE or PBO + EXE. The primary endpoint was PFS by local investigator assessment. Main secondary endpoints included centrally assessed PFS, overall survival (OS), safety, bone turnover, and overall response rate (ORR). Results: Baseline disease characteristics including tumor burden and prior cancer therapy were well balanced between treatment arms (N = 724). Median PFS was doubled and response rates were consistently improved with EVE + EXE (n = 485) vs PBO + EXE (n = 239) in interim analyses. Median PFS by local assessment was ~3 mo with PBO + EXE vs 6.9 mo (hazard ratio [HR] = 0.43; P < .0001) and 7.4 mo (HR = 0.44; P < .0001) with EVE + EXE at 7.5 mo and 12.5 mo follow-up, respectively. Fewer deaths were reported with EVE + EXE (17.2%) vs PBO + EXE (22.7%) at 12.5 mo follow-up. Safety profiles were consistent with previous reports for mTOR inhibitors. PFS data including 528 events (protocol-specified final analysis), and updated OS and safety data will be presented. Conclusions: Adding EVE to EXE markedly prolonged PFS in patients with NSAI-refractory advanced ER+ BC. There were fewer deaths among patients receiving EVE, and further follow-up will evaluate the effect of EVE on OS.

A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC: Follow-up results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7016-7016 ◽  
Author(s):  
J. V. Heymach ◽  
B. E. Johnson ◽  
D. Prager ◽  
E. Csada ◽  
J. Roubec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Locally Advanced ◽  
Primary Objective ◽  
Phase Iii ◽  
Double Blind Study ◽  
Once Daily ◽  
Platinum Based Chemotherapy

7016 Background: ZD6474, a once-daily oral agent, targets key signaling pathways in cancer by inhibiting VEGF, EGF and RET receptor tyrosine kinases. ZD6474 in combination with docetaxel (Doc) was assessed in patients (pts) with refractory non-small-cell lung cancer (NSCLC). Methods: Pts eligible for this randomized, double-blind study had locally advanced or metastatic (stage IIIB/IV) NSCLC after failure of 1st-line platinum-based chemotherapy. The primary objective was to determine whether once-daily oral ZD6474 (100 or 300 mg) + Doc (75 mg/m2 i.v. infusion every 21 days) prolonged progression-free survival (PFS) vs Doc alone (80% power to detect 50% prolongation at P<0.2). Overall survival was a secondary objective. Results: A total of 127 pts (73 male/54 female; median age 59 yrs, range 29–82) received ZD6474 100 mg + Doc (n=42), ZD6474 300 mg + Doc (n=44) or Doc (n=41). The study met its primary objective of PFS prolongation with the addition of ZD6474: median PFS was 19 wks for ZD6474 100 mg + Doc (HR=0.64; P=0.074); 17 wks for ZD6474 300 mg + Doc (HR=0.83; P=0.461); and 12 wks for Doc. A total of 64 pts (50%) presented with histology other than adenocarcinoma, including 37 with squamous, and 13 pts (10%) entered with CNS metastases. Exploratory subgroup analyses suggest advantages in PFS for ZD6474 + Doc vs Doc both for adenocarcinoma and for other lung cancer histologies. Common adverse events (AEs) included diarrhea, rash and asymptomatic QTc prolongation, all responded to standard management or dose interruption/reduction. Four pts with squamous experienced hemoptysis (ZD6474 100 mg + Doc, n=2 CTC grade 1/2; Doc, n=2 CTC grade 3/4). No fatal episodes of hemoptysis or any CNS hemorrhage AEs were reported in pts receiving ZD6474. Overall survival data were immature at the time of PFS analysis, and a mature survival analysis will be conducted at ∼75% of deaths (anticipated April 2006, and will be presented at the meeting). As of December 2005, 40/127 (31%) pts were alive, 5 of whom continue to receive ZD6474. The minimum follow-up of pts still alive was 17 months. Conclusions: ZD6474 + Doc prolonged PFS vs Doc alone, and these promising data have led to the initiation of Phase III evaluation of ZD6474 + Doc in 2nd-line NSCLC. [Table: see text]

Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Francis P. Arena ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
Howard A. Burris ◽  
Hope S. Rugo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Aromatase Inhibitor ◽  
Postmenopausal Women ◽  
Survival Data ◽  
Safety Data ◽  
Phase Iii ◽  
Once Daily ◽  
Estrogen Receptor Positive

99 Background: Current treatment options for postmenopausal patients with estrogen-receptor–positive breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) are limited. The BOLERO-2 trial supports the activity of everolimus (EVE; an oral mammalian target of rapamycin [mTOR] inhibitor) added to the steroidal aromatase inhibitor exemestane (EXE) to prolong progression-free survival (PFS) in this patient population. Long-term PFS and survival data are awaited. Methods: BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing EVE (10 mg once daily) + EXE (25 mg once daily) vs. placebo (PBO) + EXE in postmenopausal women with advanced estrogen-receptor–positive BC progressing or recurring after NSAIs (letrozole or anastrozole). Patients were randomized (2:1) to EVE + EXE or PBO + EXE. The primary endpoint was PFS by local investigator assessment. Main secondary endpoints included centrally assessed PFS, overall survival (OS), safety, bone turnover, and overall response rate. Results: Baseline disease characteristics including tumor burden and prior cancer therapy were well balanced between treatment arms (N = 724). Median PFS was doubled and response rates were consistently improved with EVE + EXE (n = 485) vs PBO + EXE (n = 239) in interim analyses. Median PFS by local assessment was ~3 mo with PBO + EXE vs 6.9 mo (hazard ratio [HR], 0.43; P < .0001) and 7.4 mo (HR, 0.44; P < .0001) with EVE + EXE at 7.5 mo and 12.5 mo follow-up, respectively. Fewer deaths were reported with EVE + EXE (17.2%) vs PBO + EXE (22.7%) at 12.5 mo follow-up. Safety profiles were consistent with previous reports for mTOR inhibitors. PFS data including 528 events (protocol-specified final analysis), and updated OS and safety data will be presented. Conclusions: Adding EVE to EXE markedly prolonged PFS in patients with NSAI-refractory advanced estrogen-receptor–positive BC. There were fewer deaths among patients receiving EVE, and further follow-up will evaluate the effect of EVE on OS.

Avelumab in patients with previously treated Merkel cell carcinoma (JAVELIN Merkel 200): Updated overall survival data after more than five years of follow up.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9517-9517
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Andrew S. Brohl ◽  
Omid Hamid ◽  
Janice M. Mehnert ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Disease Progression ◽  
Merkel Cell Carcinoma ◽  
Survival Data ◽  
Safety Data ◽  
Additional Patient ◽  
Merkel Cell

9517 Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is considered chemosensitive, patients typically have limited survival benefit with chemotherapy. Before the approval of immune checkpoint inhibitors, patients with metastatic MCC (mMCC) had a poor prognosis, with a historical 5-year overall survival (OS) rate of approximately 14%. Avelumab (anti–PD-L1) became the first approved treatment for patients with mMCC, based on efficacy and safety data observed in the phase 2 JAVELIN Merkel 200 trial (NCT02155647), in which patients with mMCC received avelumab monotherapy. We report the long-term OS data from the cohort of patients with mMCC whose disease had progressed after ≥1 prior line of chemotherapy. Methods: Eligible patients had histologically confirmed, measurable (per RECIST 1.1) stage IV MCC. Patients received avelumab 10 mg/kg by intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxicity, or withdrawal. Long-term OS was analyzed; updated data for other efficacy endpoints, including response and progression-free survival, were not obtained. Results: A total of 88 patients were enrolled and received avelumab treatment. As of September 25, 2020 (data cutoff), median follow-up was 65.1 months (range, 60.8-74.1 months). Median OS was 12.6 months (95% CI, 7.5-17.1 months); the 48- and 60-month OS rates were 30% (95% CI, 20%-40%) and 26% (95% CI, 17%-36%), respectively. At data cutoff, treatment was ongoing in 1 patient (1.1%) and an additional patient (1.1%) had reinitiated avelumab after previously discontinuing treatment. Reasons for treatment discontinuation were disease progression (n = 45 [51.1%]), adverse event (AE; n = 11 [12.5%]), death (n = 10 [11.4%]), withdrawal of consent (n = 9 [10.2%]), loss to follow-up (n = 1 [1.1%]), protocol noncompliance (n = 1 [1.1%]), and other reason (n = 10 [11.4%]). At data cutoff, 19 patients (21.6%) had discontinued treatment but remained in follow-up, and 63 patients (71.6%) had died; causes of death were disease progression (n = 49 [55.7%]), unknown reason (n = 9 [10.2%]), AE not related to study treatment (n = 3 [3.4%]), and other reason (n = 2 [2.3%]). In total, 26 patients (29.5%) received subsequent anticancer therapy; the most common subsequent therapies after trial discontinuation were avelumab (n = 4 [4.5%]), carboplatin and etoposide (n = 4 [4.5%]), and pembrolizumab (n = 4 [4.5%]). Conclusions: Avelumab monotherapy led to meaningful long-term OS in a subset of patients with mMCC whose disease had progressed after chemotherapy. These results further support the role of avelumab as a standard-of-care treatment for patients with mMCC. Clinical trial information: NCT02155647.

A phase III study of nivolumab (Nivo) in previously treated advanced gastric or gastric esophageal junction (G/GEJ) cancer (ATTRACTION-2): Three-year update data.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 383-383 ◽  
Author(s):  
Li-Tzong Chen ◽  
Yoon-Koo Kang ◽  
Taroh Satoh ◽  
Yee Chao ◽  
Ken Kato ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Subgroup Analysis ◽  
Survival Data ◽  
Phase Iii ◽  
Term Survival ◽  
Heavily Pretreated ◽  
Long Term Follow Up ◽  
Patient Enrollment

383 Background: Nivo is the first immune checkpoint inhibitor (ICI) to show efficacy and tolerability in G/GEJ cancer patients refractory to or intolerant of standard chemotherapy. Although Nivo has demonstrated durable efficacy in several cancer types, no long-term efficacy data in G/GEJ cancer has been reported to date. Here, we report the 3-year survival data of Nivo in G/GEJ cancer. Methods: A total of 493 patients with unresectable advanced or recurrent G/GEJ cancer after the failure of two or more chemotherapy regimens were randomized in a 2:1 ratio to receive 3 mg/kg Nivo (N = 330) or placebo (N = 163) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Updated results of the efficacy and safety were based on ≥ 3 years of follow-up after last patient enrollment. In subgroup analysis, we evaluated OS by BOR and incidence of select treatment-related adverse events (TRAEs). Results: As of data cut-off in February 2019, 3 years after last patient enrollment, the hazard ratios of OS and PFS in the Nivo group compared with the placebo group remained 0.62 and 0.60, respectively. The 36-month OS rates of Nivo and placebo were 5.6% and 1.2 % and the 36-month PFS rates were 2.4% and 0%, respectively. In the OS subgroup analysis by BOR, the median OS and 3-year OS rate in CR/PR patients with Nivo were 26.7 months and 35.5%, respectively. The incidence rate and severity of TRAEs were comparable with those of the 2-year cut-off. In the OS subgroup analysis based on the presence or absence of select TRAEs, the hazard ratio in patients with select TRAEs was 0.46 compared to those without select TRAEs. We are analyzing the baseline characteristics that are associated with long-term survival with Nivo. Conclusions: Nivo showed durable efficacy and a good safety profile on long-term follow-up in heavily pretreated G/GEJ cancer patients. Clinical trial information: NCT02267343.

scholarly journals CTIM-28. PHASE 2 TRIAL OF CONTROLLED IL-12 IN COMBINATION WITH PD-1 INHIBITOR IN ADULT SUBJECTS WITH RECURRENT GLIOBLASTOMA (rGBM)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii39-ii39
Author(s):  
Rimas Lukas ◽  
E Antonio Chiocca ◽  
Nancy Ann Oberheim Bush ◽  
Joseph Landolfi ◽  
Robert Cavaliere ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Data ◽  
Phase 1 ◽  
Safety Data ◽  
Recurrent Glioblastoma ◽  
Preliminary Review ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Immune Mediated

Abstract Ad-RTS-hIL-12 (Ad) is a gene therapy candidate for intratumoral (IT) delivery that conditionally expresses IL-12 (IL-12) under the transcriptional control of orally administered veledimex (V) acting via the RheoSwitch Therapeutic Systemâ gene switch. Increased PD-1 expression in samples of rGBM following Ad+V (ASCO 2020) supports combination immunotherapy with a PD-1 inhibitor. Phase 1 trials in rGBM of Ad+V as monotherapy and in combination with PD-1 inhibitor revealed encouraging safety and survival data. This phase 2 trial (NCT04006119) in adults with rGBM is evaluating safety and efficacy (overall survival) of Ad + V with pre/post-operative cemiplimab-rwlc (cemi) 350 mg IV, Days -7, 15, then Q3W; Ad single IT injection (2 x 1011 viral particles, day of resection (Day 0) /craniotomy); and V (20 mg PO, Days 0–14). Longitudinal sampling of serum assessed IL-12 and endogenous cytokines production. Anti-tumor effects were described upon preliminary review. Serial MRI evaluated tumor response. Follow-up described overall survival. Initial safety data (51 unique adverse reactions in 28 subjects) appeared similar to Ad+V and the cemi label, respectively, being manageable without synergistic toxicities and generally reversible. Of 35 SAEs reported in 18 subjects, 10 SAEs in 7 subjects were related to Ad+V. IL-12 and IFN-g levels increased after Ad+V administration peaking on Day 3 at 34 ± 11 pg/mL and 13 ± 5 pg/mL (mean ± SEM), respectively. Immune-mediated anti-tumor effects were noted, including a post-treatment biopsy to rule out progression which demonstrated an immune infiltrate consistent with pseudoprogression and loss of tumor cell heterogeneity suggesting immunoediting. Enrollment is anticipated to be completed in 2Q2020 with follow-up ongoing and initial survival data will be presented. V crossed the blood-brain barrier to produce functional IL-12. Controlled IL-12 therapy and cemi is a rational combination with initial data consistent with immune-mediated anti-tumor effects with a favorable safety profile.

scholarly journals Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

2011 ◽  
Vol 29 (34) ◽  
pp. 4491-4497 ◽  
Author(s):  
Edith A. Perez ◽  
Vera J. Suman ◽  
Nancy E. Davidson ◽  
Julie R. Gralow ◽  
Peter A. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
P Value ◽  
Sequential Administration ◽  
Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

Final overall survival in the phase 3 NETTER-1 study of lutetium-177-DOTATATE in patients with midgut neuroendocrine tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4112-4112
Author(s):  
Jonathan R. Strosberg ◽  
Martyn E Caplin ◽  
Pamela L. Kunz ◽  
Philippe B Ruszniewski ◽  
Lisa Bodei ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neuroendocrine Tumors ◽  
High Dose ◽  
Radioligand Therapy ◽  
Phase 3 ◽  
Long Term Follow Up ◽  
Long Acting ◽  
Safety Signals

4112 Background: As demonstrated in the primary analysis of the phase 3 NETTER-1 trial, 177Lu-DOTATATE significantly prolonged progression-free survival (PFS) versus high-dose long-acting octreotide, with a HR of 0.18 (95% CI: 0.11, 0.29; p < 0.0001), in patients with advanced, progressive, well-differentiated, somatostatin receptor-positive midgut neuroendocrine tumors (NETs). Here we report final overall survival (OS) for NETTER-1. Methods: In this international open-label trial, eligible patients were randomized to receive either four cycles of 177Lu-DOTATATE 7.4 GBq (200 mCi) every 8 ± 1 weeks plus long-acting octreotide 30 mg or high-dose long-acting octreotide 60 mg every 4 weeks (control arm), both on top of best supportive care. After disease progression on randomized treatment or completion of an 18-month treatment period, patients in both arms entered long-term follow-up and could receive further anti-cancer treatment as recommended by their physicians. The primary endpoint was PFS per RECIST 1.1 and OS was a key secondary endpoint. Primary intention-to-treat analysis of OS was prespecified to take place after 158 deaths or 5 years after the last patient was randomized, whichever occurred first. Results: Of 231 randomized patients, 101/117 (86.3%) in the 177Lu-DOTATATE arm and 99/114 (86.8%) in the control arm entered long-term follow-up. Final analysis occurred 5 years after the last patient was randomized, following 142 deaths, with a median follow-up of more than 76 months. During long-term follow-up, 41/114 (36%) of patients in the control arm received subsequent radioligand therapy (“cross-over”), the majority (22.8%) within 24 months. Median OS was 48.0 months (95% CI: 37.4, 55.2) in the 177Lu-DOTATATE arm and 36.3 months (95% CI: 25.9, 51.7) in the control arm. HR was 0.84 (95% CI: 0.60, 1.17) with p = 0.30 (unstratified 2-sided log-rank test). A total of 2/112 (1.8%) 177Lu-DOTATATE treated patients in the study developed myelodysplastic syndrome (MDS). No new cases of MDS or acute leukemia were reported in the long-term follow-up. Overall, no new safety signals emerged during long-term follow-up. Conclusions: Median OS was 48.0 months in the 177Lu-DOTATATE arm of the NETTER-1 trial and 36.3 months in the control arm. This difference was not statistically significant, potentially impacted by a high rate (36%) of cross-over of patients in the control arm to radioligand therapy after progression. In overall conclusion, the NETTER-1 study demonstrated that 177Lu-DOTATATE yielded a clinically and statistically significant improvement in PFS as a primary endpoint (HR: 0.18, p < 0.0001) as well as a clinically meaningful trend towards improvement in median OS of 11.7 months. No new safety signals emerged during the 5-year long-term follow-up. Clinical trial information: NCT01578239.

Safety of darolutamide (DARO) for nonmetastatic castration-resistant prostate cancer (nmCRPC) from extended follow-up in the phase III ARAMIS trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 239-239
Author(s):  
Matthew Raymond Smith ◽  
Karim Fizazi ◽  
Teuvo L. J. Tammela ◽  
Felipe Melo Cruz ◽  
Luke T. Nordquist ◽  
...  
Keyword(s):  
Safety Profile ◽  
Safety Data ◽  
Final Analysis ◽  
Phase Iii ◽  
Prolonged Treatment ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Favorable Safety Profile ◽  
Risk Of Death ◽  
Favorable Safety

239 Background: DARO is a structurally distinct androgen receptor inhibitor (ARI) approved for treating nmCRPC. In ARAMIS, DARO significantly reduced the risk of death by 31% (HR = 0.69; 95% CI: 0.53-0.88; p = 0.003) and prolonged median metastasis-free survival vs placebo (PBO; 40.4 months vs 18.4 months; HR = 0.41; 95% CI: 0.34-0.50; p < 0.001). Adverse events (AEs) of interest commonly associated with ARI therapy, such as fatigue, falls, fractures, rash, mental impairment, and hypertension, as well as interactions between ARIs and concomitantly administered drugs, can impact patient daily life. In the final analysis of the double-blind (DB) period of the ARAMIS trial, DARO had a favorable safety profile, showing ≤2% difference vs PBO for most AEs of interest. Fatigue was the only AE with > 10% incidence with DARO. The incidence of permanent discontinuation due to AEs was also similar between DARO and PBO (8.9% vs 8.7%). Here we present safety data for prolonged treatment with DARO from the final analysis of the DB + open-label (OL) period of ARAMIS. Methods: Patients (pts) with nmCRPC (N = 1509) were randomized 2:1 to DARO or matched PBO while continuing androgen deprivation therapy. The data cut-off for the primary analysis of the DB period was September 3, 2018. Study unblinding occurred on November 30, 2018, after which pts in the DARO arm still receiving study treatment continued with OL DARO. The data cut-off for final analysis of the DB+OL period was November 15, 2019. Results: At the final analysis, the median treatment duration for pts randomized to DARO was 18.5 months for the DB period and 25.8 months for the DB+OL period. At the final cut-off date, 48.8% of patients in the DARO DB+OL group were still receiving DARO treatment. The increase in the incidence of any-grade AEs (85.7% vs 89.8%) and serious AEs (26.1% vs 32.1%) between the DB and DB+OL period was small. Between the DB and DB+OL periods, only minor numerical changes for ARI-associated AEs were observed. When the incidences were corrected for exposure, there were minimal differences between the DB and DB+OL period, e.g., the fracture rate was 3.4 vs 4.0 per 100 patient-years for the DB vs DB+OL periods, respectively. Fatigue was the only ARI-associated AE of interest that exhibited > 10% incidence in the DARO arm during the DB+OL period. The incidence of permanent discontinuation of DARO due to AEs increased slightly from 8.9% during the DB period to 10.5% during the DB+OL period; the incidence of discontinuation of PBO due to AEs during the DB period was 8.7%. Conclusions: With longer treatment exposure, DARO remained well-tolerated. In the DB+OL period, no new safety signals were observed. The expected increases in incidence of AEs between the DB and DB+OL periods largely disappeared when adjusted for the longer exposure, confirming the favorable safety profile of DARO with prolonged treatment. Clinical trial information: NCT02200614.

Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

2009 ◽  
Vol 27 (22) ◽  
pp. 3664-3670 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standards Of Care ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
To Receive

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

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