scholarly journals Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery: study protocol of a randomized multi-center phase III trial—AkniPro 2

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christian Scheller ◽  
Christian Strauss ◽  
Sandra Leisz ◽  
Pia Hänel ◽  
Ariane Klemm ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Standard Of Care ◽  
Hearing Preservation ◽  
Cochlear Nerve ◽  
Phase Iii ◽  
Control Group ◽  
Nerve Function ◽  
Speech Discrimination ◽  
Phase Iii Trial ◽  
Patient Reported

Abstract Background A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18–1.30; p = 0.15). Accordingly, this phase III extension trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery. Methods This is a randomized, multi-center, two-armed, open-label phase III trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I–IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1–3) are assigned to either the therapy (intravenous nimodipine 1–2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the trial is postoperative cochlear nerve function measured before discharge according to GR 1–3 versus GR 4–5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed. Discussion Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient’s quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since hearing outcome can be classified by well-recognized criteria. The beneficial effect of nimodipine may be transferable to other surgical procedures with nerves at risk and may have impact on basic research. Trial registration EudraCT 2019-002317-19, DRKS00019107. 8th May 2020.

Stability of hearing preservation and regeneration capacity of the cochlear nerve following vestibular schwannoma surgery via a retrosigmoid approach

2016 ◽  
Vol 125 (5) ◽  
pp. 1277-1282 ◽  
Author(s):  
Christian Scheller ◽  
Andreas Wienke ◽  
Marcos Tatagiba ◽  
Alireza Gharabaghi ◽  
Kristofer F. Ramina ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Strong Association ◽  
Pure Tone Audiometry ◽  
Hearing Preservation ◽  
Cochlear Nerve ◽  
Speech Discrimination ◽  
Regeneration Capacity ◽  
Postoperative Course ◽  
Link Type ◽  
Hearing Abilities

OBJECTIVE The purpose of this research was to examine the stability of long-term hearing preservation and the regeneration capacity of the cochlear nerve following vestibular schwannoma (VS) surgery in a prospective study. METHODS A total of 112 patients were recruited for a randomized multicenter trial between January 2010 and April 2012 to investigate the efficacy of prophylactic nimodipine treatment versus no prophylactic nimodipine treatment in VS surgery. For the present investigation, both groups were pooled to compare hearing abilities in the early postoperative course and 1 year after the surgery. Hearing was examined using pure-tone audiometry with speech discrimination, which was performed preoperatively, in the early postoperative course, and 12 months after surgery and was subsequently classified by an independent otorhinolaryngologist using the Gardner-Robertson classification system. RESULTS Hearing abilities at 2 time points were compared by evaluation in the early postoperative course and 1 year after surgery in 102 patients. The chi-square test showed a very strong association between the 2 measurements in all 102 patients (p < 0.001) and in the subgroup of 66 patients with a preserved cochlear nerve (p < 0.001). CONCLUSIONS There is no significant change in cochlear nerve function between the early postoperative course and 1 year after VS surgery. The result of hearing performance, as evaluated by early postoperative audiometry after VS surgery, seems to be a reliable prognosticator for future hearing ability. Clinical trial registration nos.: 2009-012088-32 (clinicaltrialsregister.eu) and DRKS 00000328 (“AkNiPro,” drks-neu.uniklinik-freiburg.de/drks_web/)

Tumor origin and hearing preservation in vestibular schwannoma surgery

2011 ◽  
Vol 115 (5) ◽  
pp. 900-905 ◽  
Author(s):  
Jens Rachinger ◽  
Stefan Rampp ◽  
Julian Prell ◽  
Christian Scheller ◽  
Alex Alfieri ◽  
...  
Keyword(s):  
Vestibular Schwannoma ◽  
Tumor Size ◽  
Hearing Preservation ◽  
Vestibular Nerve ◽  
Cochlear Nerve ◽  
Nerve Function ◽  
Nerve Preservation ◽  
Tumor Origin ◽  
Inferior Vestibular Nerve ◽  
Vs Removal

Object Preservation of cochlear nerve function in vestibular schwannoma (VS) removal is usually dependent on tumor size and preoperative hearing status. Tumor origin as an independent factor has not been systematically investigated. Methods A series of 90 patients with VSs, who underwent surgery via a suboccipitolateral route, was evaluated with respect to cochlear nerve function, tumor size, radiological findings, and intraoperatively confirmed tumor origin. All patients were reevaluated 12 months after surgery. Results Despite comparable preoperative cochlear nerve status and larger tumor sizes, hearing preservation was achieved in 42% of patients with tumor originating from the superior vestibular nerve, compared with 16% of those with tumor originating from the inferior vestibular nerve. Conclusions Tumor origin is an important prognostic factor for cochlear nerve preservation in VS surgery.

scholarly journals A Systematic Review of Phase III Clinical Trials of Daratumumab Addition to Standard Care Regimen for Newly Diagnosed Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-7
Author(s):  
Zahoor Ahmed ◽  
Karun Neupane ◽  
Rabia Ashraf ◽  
Amna Khan ◽  
Moazzam Shahzad ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Standard Care ◽  
Standard Of Care ◽  
Phase Iii ◽  
Control Group ◽  
Newly Diagnosed ◽  
Phase Iii Trial ◽  
Mesh Terms ◽  
Three Phase

Introduction: In multiple myeloma (MM), plasma cells including malignant cells show expression of CD38, which is the target for daratumumab (Dara), an IgG1k monoclonal antibody, approved for MM treatment. This review highlights the efficacy and safety of Dara addition to the standard of care therapy in newly diagnosed MM (NDMM) patients (pts). Methods: We conducted a literature search using four databases (PubMed, Embase, Web of Science, and Clinicaltrials.gov). Our search strategy included MeSH terms and key words for multiple myeloma and Dara including trade names and generic names from date of inception to April 2020. A total of 587 articles were screened, and after excluding review articles, duplicates, and non-relevant articles, we included three phase III trials reporting daratumumab addition to the standard of care regimens for NDMM patients. Results: A total of 2528 patients were enrolled and evaluated in three phase III randomized controlled trials. A total of 1261 patients were in the daratumumab group and 1267 patients were in the control group. Total 1085 were transplant eligible and 1443 patients were transplant ineligible. Transplant eligible: Moreau et al. (2019) underlined the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) in NDMM pts (n=1085) in CASSIOPEIA phase III trial. Addition of Dara to VTd group showed marked improvent in progression free survival (PFS): 93% vs 85% at 18 months (hazard ratio (HR) 0.42 [0.34-0.51]; p&lt;0.0001), and overall response rate (ORR) of 92.6% (CI: 95%, P &lt;0.0001) in Dara + VTd group as compared to VTd group (89.9%). Minimal residual disease (MRD) negative status (10-⁵ sensitivity threshold, assessed by multipara metric flow cytometry) in bone marrow was 64% (P&lt;0.0001) in Dara using VTd vs 44% in VTd group. Transplant ineligible: Bahlis N et al. (2019) studied Dara + lenolidamide (R) and dexamethasone (d) in NDMM pts (n=737) in MAIA phase III trial. Mateos et al. (2018) reported the role of Dara + V + melphalan (M) + prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). Addition of Dara to Rd, and VMP group showed marked improvent in PFS: 68% vs 46% at 36 months [confidence interval [CI], 0.44-0.71; P&lt;0.0001], and 63% vs 36 at 24 months (HR: 0.47, 95% CI 0.33-0.67, p&lt;0.0001), and ORR: 93% vs 82% (P&lt;0.0001), and 90.9% vs 73.9%, respectively. MRD negative status in bone marrow was observed higher with Dara compared to without Dara using Rd (24.2% vs 7.3%) (P&lt;0.001), and Dara + VMP group (28% vs 7%) (p&lt;0.0001) respectively. Significant toxicities mainly included pancytopenias and opportunistic infections (table 2). Standard care regimen (VTd, VMP, Rd) with Dara addition achieved superior outcomes in terms of ORR and PFS. Addition of Dara improved MRD negative status. Conclusion: NDMM treatment with Dara plus standard care therapy (VTd, VMP, Rd) has shown promising outcomes and has set a benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Prophylactic nimodipine treatment for cochlear and facial nerve preservation after vestibular schwannoma surgery: a randomized multicenter Phase III trial

2016 ◽  
Vol 124 (3) ◽  
pp. 657-664 ◽  
Author(s):  
Christian Scheller ◽  
Andreas Wienke ◽  
Marcos Tatagiba ◽  
Alireza Gharabaghi ◽  
Kristofer F. Ramina ◽  
...  
Keyword(s):  
Treatment Group ◽  
Facial Nerve ◽  
Hydroxyethyl Starch ◽  
Phase Iii ◽  
Control Group ◽  
Nerve Function ◽  
Facial Nerve Function ◽  
Phase Iii Trial ◽  
Nerve Preservation ◽  
Multicenter Phase

OBJECT A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1–2 mg/hr) and hydroxyethyl starch (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34–3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18–1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.

scholarly journals Patient- versus physician-reported facial disability in vestibular schwannoma: an international cross-sectional study

2017 ◽  
Vol 127 (5) ◽  
pp. 1015-1024 ◽  
Author(s):  
Øystein Vesterli Tveiten ◽  
Matthew L. Carlson ◽  
Frederik Goplen ◽  
Erling Myrseth ◽  
Colin L. W. Driscoll ◽  
...  
Keyword(s):  
Risk Factors ◽  
Facial Nerve ◽  
Vestibular Schwannoma ◽  
Well Being ◽  
Control Group ◽  
Nerve Function ◽  
Facial Nerve Function ◽  
The Social ◽  
Patient Reported ◽  
Nerve Dysfunction

OBJECTIVEPatient-reported outcomes are increasingly used in studies of vestibular schwannoma (VS); however, few studies have examined self-evaluated facial nerve function and its relation to physician-reported outcomes. The primary objective of this study was to compare patient self-evaluations of facial disability with physician-evaluated facial nerve status and with self-evaluations of a healthy control group. The second objective was to provide insight into the controversial subject of the optimal initial management of small- and medium-sized VSs; consequently, the authors compared patient-reported facial nerve disability following treatment via observation (OBS), Gamma Knife surgery (GKS), or microsurgery (MS). Lastly, the authors sought to identify risk factors for facial nerve dysfunction following treatment for small- and medium-sized VSs.METHODSAll patients with a VS 3 cm or smaller that was singly treated with OBS, GKS, or MS at either of 2 independent treatment centers between 1998 and 2008 were retrospectively identified. Longitudinal facial nerve measures and clinical data, including facial nerve evaluation according to the House-Brackmann (HB) grading system, were extracted from existing VS databases. Supplementing the objective data were Facial Disability Index (FDI) scores, which were obtained via survey of patients a mean of 7.7 years after initial treatment.RESULTSThe response rate among the 682 eligible patients was 79%; thus, data from a total of 539 patients were analyzed. One hundred forty-eight patients had been managed by OBS, 247 with GKS, and 144 with MS. Patients who underwent microsurgery had larger tumors and were younger than those who underwent OBS or GKS. Overall, facial nerve outcomes were satisfactory following treatment, with more than 90% of patients having HB Grade I function at the last clinical follow-up. Treatment was the major risk factor for facial nerve dysfunction. Almost one-fifth of the patients treated with MS had an objective decline in facial nerve function, whereas only 2% in the GKS group and 0% in the OBS cohort had a decline. The physical subscale of the FDI in the VS patients was highly associated with HB grade; however, the social/well-being subscale of the FDI was not. Thus, any social disability caused by facial palsy was not detectable by use of this questionnaire.CONCLUSIONSThe majority of patients with small- and medium-sized VSs attain excellent long-term facial nerve function and low facial nerve disability regardless of treatment modality. Tumor size and microsurgical treatment are risk factors for facial nerve dysfunction and self-reported disability. The FDI questionnaire is sensitive to the physical but not the social impairment associated with facial dysfunction.

Systematic Review of Phase III Trials of Daratumumab Based Regimens in Relapsed Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Karun Neupane ◽  
Zahoor Ahmed ◽  
Rabia Ashraf ◽  
Amna Khan ◽  
Moazzam Shahzad ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Standard Care ◽  
Standard Of Care ◽  
Phase Iii ◽  
Control Group ◽  
Sensitivity Threshold ◽  
Phase Iii Trial ◽  
Mesh Terms ◽  
Three Phase ◽  
Phase Iii Trials

Introduction: Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cell proliferation leads to complications and death. Daratumumab (Dara) is a humanized IgGk monoclonal antibody that targets CD38- a glycoprotein expressed on plasma cells and malignant cells. Dara has direct anti-tumor effects along with immunomodulatory activities, resulting in clonal expansion of cytotoxic T cells and diminution of immunosuppressive cells. This review highlights the efficacy and safety of Dara addition to the standard of care regimen, tested in Phase III trials, in patients with relapsed refractory MM (RRMM). Methods: We conducted a systematic literature search in four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov) using MeSH terms and keywords for multiple myeloma and Dara including trade names and generic names from date of inception to April 2020. Initial search revealed 587 articles. After excluding review articles, duplicates, and non-relevant articles, we included three phase III trials reporting daratumumab addition to the standard of care regimens for RRMM patients. Results: A total of 1521 patients out of 1533 enrolled patients were evaluated in three phase III randomized controlled trials. A total of 849 patients were evaluated in the Dara group and 684 patients were evaluated in the control group. Catja. C et al. (2019) studied the role of Dara + bortezomib (V) + dexamethasone (d) in RRMM pts (n=498) in phase III trial (CASTOR). Saad Z.U et al. (2019) underlined the efficacy of Dara + carfilzomib (K) and (d) in RRMM pts (n=466) in phase III trial (CANDOR), and Nizar J. Bahlis et al. (2020) studied Dara + lenolidamide (R) + d in RRMM pts (n=569) in phase III trial (POLLUX). The addition of Dara to Vd, Rd, and Kd group was significant in term of overall response rate (ORR): 85% vs 63% (P &lt;0.0001), 93% vs 76% (P &lt; 0.0001), and 84.3% vs 74.7% (p=0.004), and minimal residual disease (MRD) negative status ((10-⁵ sensitivity threshold, assessed by multipara metric flow cytometry) in bone marrow: 11.6% vs 2.4% (P=0.000034), 30.4% vs 5.3% (P&lt;0.0001), and 12.5% vs 1.3% (p&lt;0.0001) group, respectively. Moreover, addition of Dara to Vd, and Rd group also showed marked improvement in progression free survival (PFS): 48% vs 7.9% (HR, 0.31; 95% CI, 0.25-0.39, P &lt;0.0001) at 18 months, 44.5% vs 17.5% at 44 months (HR, 0.44; 95% CI, 0.35-0.55; P &lt; 0.0001), and OS: 61% vs 51% at three years, and 65% vs 57% at 42 months, respectively. However, PFS and OS in Dara-Kd group was not reached vs control group: Kd group (HR= 0.63, 95% CI, 0.46-0.85, p=0.0014). Significant toxicities mainly included neutropenia, anemia, and thrombocytopenia (table 2). Addition of Dara to standard care regimen (Vd and Rd) achieved superior outcomes in terms of ORR, PFS and OS, except Kd group, in which only ORR was improved as compared to control group. Combination of Dara plus standard care regimen improved MRD negative status in RRMM patients as compared to standard regimen. Conclusion: Treatment of RRMM with Dara plus standard care therapy (Vd, Rd, and Kd) has shown promising outcomes with improved efficacy and higher negative MRD status, providing a new benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celgene, Millennium Pharmaceuticals,: Honoraria, Research Funding, Speakers Bureau.

Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study

2017 ◽  
Vol 127 (6) ◽  
pp. 1376-1383 ◽  
Author(s):  
Christian Scheller ◽  
Andreas Wienke ◽  
Marcos Tatagiba ◽  
Alireza Gharabaghi ◽  
Kristofer F. Ramina ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Pilot Study ◽  
Treatment Group ◽  
Vestibular Schwannoma ◽  
Lower Risk ◽  
Small Sample ◽  
Phase Iii ◽  
Control Group ◽  
Phase Iii Trial ◽  
Class D

OBJECTIVEIn clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled.METHODSThe patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1–2 mg/hour) and HES (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery.RESULTSPooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22–0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17–0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09–0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated.CONCLUSIONSProphylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept.Clinical trial registration no.: DRKS 00000328 (https://drks-neu.uniklinik-freiburg.de/drks_web/)

Five-year survival outcomes with durvalumab after chemoradiotherapy in unresectable stage III NSCLC: An update from the PACIFIC trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8511-8511
Author(s):  
David R. Spigel ◽  
Corinne Faivre-Finn ◽  
Jhanelle Elaine Gray ◽  
David Vicente ◽  
David Planchard ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Stage Iii ◽  
Smoking History ◽  
Kaplan Meier ◽  
Unresectable Stage ◽  
The Pacific ◽  
Patient Reported ◽  
Stage Iii Nsclc

8511 Background: In the placebo-controlled Phase III PACIFIC trial of patients with unresectable Stage III NSCLC whose disease had not progressed after platinum-based concurrent chemoradiotherapy (cCRT), durvalumab improved overall survival (OS) (stratified hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53–0.87; p=0.0025; data cutoff [DCO] Mar 22, 2018) and progression-free survival (PFS) (stratified HR 0.52, 95% CI 0.42–0.65; p<0.0001; DCO Feb 13, 2017) based on the DCOs used for the primary analyses, and the degree of benefit remained consistent in subsequent updates. Durvalumab was associated with a manageable safety profile, and did not detrimentally affect patient-reported outcomes, compared with placebo. These findings established consolidation durvalumab after CRT (the ‘PACIFIC regimen’) as the standard of care in this setting. We report updated, exploratory analyses of OS and PFS, assessed approximately 5 years after the last patient was randomized. Methods: Patients with WHO PS 0/1 (and any tumor PD-L1 status) whose disease did not progress after cCRT (≥2 overlapping cycles) were randomized (2:1) 1–42 days following cCRT (total prescription radiotherapy dose typically 60–66 Gy in 30–33 fractions) to receive 12 months’ durvalumab (10 mg/kg IV every 2 weeks) or placebo, stratified by age (<65 vs ≥65 years), sex, and smoking history (current/former smoker vs never smoked). The primary endpoints were OS and PFS (blinded independent central review; RECIST v1.1) in the intent-to-treat (ITT) population. HRs and 95% CIs were estimated using stratified log-rank tests in the ITT population. Medians and OS/PFS rates at 60 months were estimated with the Kaplan–Meier method. Results: Overall, 709/713 randomized patients received treatment in either the durvalumab (n/N=473/476) or placebo (n/N=236/237) arms. The last patient had completed study treatment in May 2017. As of Jan 11, 2021 (median follow-up duration of 34.2 months in all patients; range, 0.2–74.7 months), updated OS (stratified HR 0.72, 95% CI 0.59–0.89; median 47.5 vs 29.1 months) and PFS (stratified HR 0.55, 95% CI 0.45–0.68; median 16.9 vs 5.6 months) remained consistent with the results from the primary analyses. The 60-month OS rates were 42.9% and 33.4% with durvalumab and placebo, respectively, and 60-month PFS rates were 33.1% and 19.0%, respectively. Updated treatment effect estimates for patient subgroups will be presented. Conclusions: These updated survival analyses, based on 5-year data from PACIFIC, demonstrate robust and sustained OS plus durable PFS benefit with the PACIFIC regimen. An estimated 42.9% of patients randomized to durvalumab remain alive at 5 years and approximately a third remain both alive and free of disease progression. Clinical trial information: NCT02125461.

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