Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma

<h3>Objective:</h3> The objective of this study was to evaluate the impact of molecular markers (PTEN, TP53, EGFR, and TERT) on overall survival (OS) and progression-free survival (PFS) of SPARE trial patients. <h3>Background:</h3> SPARE trial (Scalp-sparing radiation with concurrent temozolomide (TMZ) and tumor treating fields; NCT03477110) is a single-arm pilot study that demonstrated the safety and feasibility of concurrent TTF with chemoradiation for newly diagnosed glioblastomas (GBM). <h3>Design/Methods:</h3> This is a secondary analysis of the SPARE trial. Molecular markers of histologically-confirmed, IDH-wildtype GBM patients age ≥ 18 years old with a Karnofsky performance status (KPS) ≥ 60 who received concurrent chemoradiation and TTF followed by maintenance TMZ + TTF were evaluated. Molecular profile was evaluated with next-generation sequencing. Interaction of mutations in PTEN, TP53, EGFR, and TERT with TTF on OS and PFS was evaluated using a multivariable model. <h3>Results:</h3> A total of 30 patients were enrolled in the SPARE trial. 1 patient with IDH-mutant histology was excluded. The median age was 58 (range; 19–77). The median KPS was 90 (range; 70–100). 9 patients (31.0% ) had a methylated MGMT promotor. 14 patients (48.3%) were found to have PTEN mutation, 9 patients (31.0%) with EGFR alteration, 7 (24.1%) with TP53 mutation, and 23 patients (79.3%) with TERT mutated. MGMT methylation remained statistically significant for an increased OS (p=0.032; HR 7.18). TERT had a statistically significant OS benefit (p=0.012; HR 7.60). TERT also showed significant improvement in PFS. However, neither EGFR, TP53, nor PTEN showed any association of PFS or OS for patients who received concurrent TTF and chemoradiation treatment. <h3>Conclusions:</h3> In this secondary analysis, neither EGFR, TP53, nor PTEN mutation showed any association of PFS or OS. However, patients with TERT mutations showed improved OS. Due to the small sample size, further validation studies should be conducted. <b>Disclosure:</b> Ms. Kayne has nothing to disclose. Dr. Poiset has nothing to disclose. Dr. Ali has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Niazi has nothing to disclose. Dr. Cappelli has nothing to disclose. The institution of Dr. Alnahhas has received research support from Novocure. Dr. Shi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novocure. Dr. Shi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for zai lab. Dr. Shi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for varian. Dr. Shi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for novocure.

Improvement in Survival of Multiple Myeloma Patients: A Long-Term Institutional Experience

Tumor-treating fields (TTFields) therapy improves both progression-free and overall survival in patients with glioblastoma. There is a need to assess the influence of TTFields on patients' health-related quality of life (HRQoL). To examine the association of TTFields therapy with progression-free survival and HRQoL among patients with glioblastoma. This secondary analysis of EF-14, a phase 3 randomized clinical trial, compares TTFields and temozolomide or temozolomide alone in 695 patients with glioblastoma after completion of radiochemotherapy. Patients with glioblastoma were randomized 2:1 to combined treatment with TTFields and temozolomide or temozolomide alone. The study was conducted from July 2009 until November 2014, and patients were followed up through December 2016. Temozolomide, 150 to 200 mg/m2/d, was given for 5 days during each 28-day cycle. TTFields were delivered continuously via 4 transducer arrays placed on the shaved scalp of patients and were connected to a portable medical device. Primary study end point was progression-free survival; HRQoL was a predefined secondary end point, measured with questionnaires at baseline and every 3 months thereafter. Mean changes from baseline scores were evaluated, as well as scores over time. Deterioration-free survival and time to deterioration were assessed for each of 9 preselected scales and items. Of the 695 patients in the study, 639 (91.9%) completed the baseline HRQoL questionnaire. Of these patients, 437 (68.4%) were men; mean (SD) age, 54.8 (11.5) years. Health-related quality of life did not differ significantly between treatment arms except for itchy skin. Deterioration-free survival was significantly longer with TTFields for global health (4.8 vs 3.3 months; P < .01); physical (5.1 vs 3.7 months; P < .01) and emotional functioning (5.3 vs 3.9 months; P < .01); pain (5.6 vs 3.6 months; P < .01); and leg weakness (5.6 vs 3.9 months; P < .01), likely related to improved progression-free survival. Time to deterioration, reflecting the influence of treatment, did not differ significantly except for itchy skin (TTFields worse; 8.2 vs 14.4 months; P < .001) and pain (TTFields improved; 13.4 vs 12.1 months; P < .01). Role, social, and physical functioning were not affected by TTFields. The addition of TTFields to standard treatment with temozolomide for patients with glioblastoma results in improved survival without a negative influence on HRQoL except for more itchy skin, an expected consequence from the transducer arrays. clinicaltrials.gov Identifier: NCT00916409.

Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial.

Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial

e12514 Background: A systematic review of patients affected with primary brain cancer treated with post-operative TMZ+RT and TMZ maintenance was undertaken in order to evaluate the efficacy and toxicity in an unselected population. Methods: Ninety-nine patients were detected. Main characteristics were: median age 62 years (range 28-80); M/F: 58/41; PS 0/1: 92 pts; complete resection: 20; subtotal resection: 75, biopsy only: 4. The median RT dose delivered was 60 Gy (range 40-60 Gy). All the 99 pts received TMZ at 75 mg/m2 concomitantly to RT. Maintenance therapy with TMZ was given to non progressive pts, starting 6 weeks after chemoradiation, at the dose of 150 mg/m2 for the 1st cycle and 200 mg/m2 q 4 weeks d. 1-5 for subsequent cycles and continued until disease progression or intolerance. Results: Patients with evaluable disease (n=79 pts) had an overall response rate of 16% (12 partial response and 1 complete response), while a stable disease was observed in 49/79 pts (62%). Maintenance TMZ was given to 77/99 pts (78%). Hematologic toxicities (CTCAE v.3) include: Gr. 3/4 neutropenia (4%), febrile neutropenia (1%), Gr. 3/4 thrombocytopenia (13%), Gr. 3 anemia (1%). One pt developed a bone marrow aplasia and another one a Steven-Johnson syndrome recovered after high supportive treatment. Toxicities caused discontinuation of TMZ in 9 patients (11%). At 2-yrs, at both univariate and multivariate analysis, a significant improvement in progression-free survival (PFS) and in overall survival (OS) was observed in pts completely resected and in pts achieving a response or a stable disease &gt;6 months. In pts achieving a response and in pts completely resected the HR for the 2-yrs PFS was 0.06 (95%CI 0.03-0.11, p&lt;0.0001) and 0.02 (95%CI 0.01-0.04, p&lt;0.0001), respectively. For the 2-yrs OS the HR was 0.08 (95%CI 0.04-0.16, p&lt;0.001) and 0.02 (95%CI 0.01-0.06, p&lt;0.0001). No difference was observed for sex, age, PS and histology. Conclusions: Complete resection, response or prolonged stabilization to maintenance TMZ are factors associated with a statistically improvement in OS and PFS.

Glioblastoma is the most devastating primary malignancy of the central nervous system in adults. Most patients die within 1 to 2 years of diagnosis. Tumor-treating fields (TTFields) are a locoregionally delivered antimitotic treatment that interferes with cell division and organelle assembly. To evaluate the efficacy and safety of TTFields used in combination with temozolomide maintenance treatment after chemoradiation therapy for patients with glioblastoma. After completion of chemoradiotherapy, patients with glioblastoma were randomized (2:1) to receive maintenance treatment with either TTFields plus temozolomide (n = 466) or temozolomide alone (n = 229) (median time from diagnosis to randomization, 3.8 months in both groups). The study enrolled 695 of the planned 700 patients between July 2009 and November 2014 at 83 centers in the United States, Canada, Europe, Israel, and South Korea. The trial was terminated based on the results of this planned interim analysis. Treatment with TTFields was delivered continuously (>18 hours/day) via 4 transducer arrays placed on the shaved scalp and connected to a portable medical device. Temozolomide (150-200 mg/m2/d) was given for 5 days of each 28-day cycle. The primary end point was progression-free survival in the intent-to-treat population (significance threshold of .01) with overall survival in the per-protocol population (n = 280) as a powered secondary end point (significance threshold of .006). This prespecified interim analysis was to be conducted on the first 315 patients after at least 18 months of follow-up. The interim analysis included 210 patients randomized to TTFields plus temozolomide and 105 randomized to temozolomide alone, and was conducted at a median follow-up of 38 months (range, 18-60 months). Median progression-free survival in the intent-to-treat population was 7.1 months (95% CI, 5.9-8.2 months) in the TTFields plus temozolomide group and 4.0 months (95% CI, 3.3-5.2 months) in the temozolomide alone group (hazard ratio [HR], 0.62 [98.7% CI, 0.43-0.89]; P = .001). Median overall survival in the per-protocol population was 20.5 months (95% CI, 16.7-25.0 months) in the TTFields plus temozolomide group (n = 196) and 15.6 months (95% CI, 13.3-19.1 months) in the temozolomide alone group (n = 84) (HR, 0.64 [99.4% CI, 0.42-0.98]; P = .004). In this interim analysis of 315 patients with glioblastoma who had completed standard chemoradiation therapy, adding TTFields to maintenance temozolomide chemotherapy significantly prolonged progression-free and overall survival. clinicaltrials.gov Identifier: NCT00916409.

Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors

728P - Randomized Phase II Trial of S-1 versus S-1 Plus Oxaliplatin (SOX) in Patients with Gemcitabine Refractory Pancreatic Cancer

Background Longer chemotherapy (CT) duration is associated with a significant improvement in progression-free survival (PFS) and a moderate, but significant improvement in overall survival (OS) in MBC patients (pts). Prolonged CT administration, however, must be weighed against the side effects of continuous CT delivery. The SNAP trial was designed to improve the tolerability of prolonged CT by studying alternative treatment schedules. Methods The SNAP trial enrolled 258 women from April 2013 to Aug 2015. Eligibility criteria included HER2- MBC, no prior CT for advanced disease, measurable and/or non-measurable disease. All eligible pts were randomized to one of three arms. Pts received the same induction chemotherapy consisting of 3 cycles of nab-Paclitaxel given days 1,8,15 Q28, followed by one of the three maintenance therapy schedules. Originally, the dose of the induction chemotherapy was 150 mg/m2, but this was reduced to 125 mg/m2 following the first safety review of 48 treated pts. The three schedules of nab-Paclitaxel used as maintenance therapy were (Arm A) nab-Paclitaxel 150 mg/m2 d 1,15 Q28; (Arm B) nab-Paclitaxel 100 mg/m2 d 1,8,15 Q28; (Arm C) nab-Paclitaxel 75 mg/m2 d 1,8,15,22 Q28. The primary objective is to evaluate the efficacy of three nab-Paclitaxel regimens as measured by progression-free survival (PFS), using the historical reference of PFS (based on AVADO study) of docetaxel for first-line treatment of metastatic breast cancer. Each of the three regimens is compared to the historic 7-month median PFS to determine whether any of the three regimens are worthy of further investigation. Secondary endpoints include tolerability, feasibility, response rate, OS and QoL. Results Two-hundred-fifty-eight pts have been randomised and 255 are available for primary endpoint evaluation. At 18.2 months' median follow-up, 182 PFS events and 85 deaths have been observed. Median PFS was 7.9 months (90%CI 6.8-8.4) in Arm A, 9.0 months (90%CI 8.1-10.9) in Arm B and 8.5 (90%CI 6.7-9.5) in Arm C. PFS in Arm B was significantly longer than the historic PFS of first-line docetaxel (one-sided log-rank p=0.03). As expected, neurotoxicity was the most frequent adverse event. In the induction phase, grade≥2 sensory neuropathy was reported in 14.8% of pts at the starting dose of 150 mg/m2 and 7.5% at the starting dose of 125 mg/m2; grade≥3 sensory neuropathy occurred in 2.5% and 0% of the pts, respectively. In the maintenance phase, grade≥2 sensory neuropathy was reported in 37.9% of pts in Arm A, 36.1% in Arm B and 31.2% in Arm C; grade≥3 sensory neuropathy occurred in 9.1%, 5.6% and 6.6% of the pts, respectively. 199 pts started the maintenance phase. The median number of maintenance cycles was 3, 4, and 5, respectively. Stopping maintenance for reasons other than objective progression occurred in 41%, 58%, and 53%, respectively. Conclusion The SNAP trial indicates that alternative maintenance chemotherapy schedules with reduced doses after a short term induction phase at conventional doses are feasible and significantly more active than the historical PFS of docetaxel in the first line treatment of advanced breast cancer. Citation Format: Gennari A, Sun Z, Hasler-Strub U, Colleoni M, Kennedy J, von Moos R, Cortes J, Vidal M, Hennessy B, Walshe J, Amillano Parraga K, Morales Murrillo S, Pagani O, Barbeaux A, Borstnar S, Rabaglio M, Maibach R, Regan MM, Jerusalem G. Randomized phase II study evaluating different schedules of nab-paclitaxel in metastatic breast cancer (MBC): Results of the SNAP study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-05.

Introduction: Recent retrospective studies suggest beta-adrenergic blocking drugs are associated with improved survival in patients with a wide range of cancers. Although limited and discordant data suggest that the use of BB may increase overall survival (OS) of patients with localized breast cancer (BC), there is no information on the effects of BB in women with advanced BC, which may be a more appropriate clinical scenario to evaluate anti-cancer effects of new treatment strategies. We analyzed the relationship between BB use and clinical outcomes in the ROSE/TRIO012 study, a double-blinded multinational registration phase III trial that randomized 1,144 patients with HER2-negative advanced BC to receive first-line docetaxel in combination with ramucirumab (RAM) or placebo. Objective: To explore the association between BB use and BC outcomes in patients participating in the ROSE/TRIO-012 trial. Methodology: We retrospectively compared PFS,OS,Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) using the ITT population, in patients who received BB during the trial with those who did not receive them. PFS and OS were estimated using the Kaplan-Meier method. PFS and OS of both treatment groups were compared using the Log-Rank test. Cox proportional models were fitted to determine the association between BB, PFS and OS. ORR and CBR in both groups were compared using the Fisher's Exact Test. Results: 153/1,144 (13%) patients received BB during the trial. Median PFS in patients treated with BB was 10.3 months, compared to 8.3 months in patients who did not receive them (HR 0.81; 95% CI 0.66-0.99; p=0.0379). In patients treated with BB only after enrolment (57/153, 37%) median PFS was 15.5 months vs. 8.3 months in patients with no BB (p=0.0005). In the subset of patients with TNBC, median PFS was 13 months if received BB compared to 5.2 months if no BB (HR 0.52; 95% CI 0.34-0.79; p=0.002). No difference in PFS was observed in patients with hormone receptor positive BC. The magnitude of PFS benefit in the RAM arm was similar as the whole ITT population (HR 0.73; 95% CI 0.57-0.94; p=0.014. If BB received only after enrolment HR 0.50; 95% CI 0.35-0.72; p=0.0003). The benefit of BB intake in PFS was independent of development of treatment-emergent hypertension (hypertension occurring within 42 days of first study drug administration; HR 0.92; 95% CI 0.73-1.15; p=0.476) but dependent on treatment arm (HR 0.86; 95% CI 0.74-0.99; p=0.037). The test for interactions between BB and treatment arm was not significant (p =0.276). No differences in OS, ORR or CBR were seen. Conclusions: In this exploratory post-hoc analysis of the ROSE/TRIO012 study, BB intake was associated with a significant improvement in PFS compared to patients who did not receive them, particularly in patients with TNBC and patients not previously exposed to these drugs. Further evaluation of the BB intake on BC outcomes warrants evaluation in a prospectively-designed clinical trial. Citation Format: Spera G, Fresco R, Fung H, Dyck JRB, Pituskin E, Patterson I, Aspeslet L, Mackey JR. Beta-adrenergic receptor blockers (BB) and increased progression free survival (PFS) in patients with advanced triple negative breast cancer (TNBC): A retrospective analysis of the ROSE/TRIO012 study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-02.

9028 Background: Toripalimab (anti-PD-1) in combination with chemotherapy showed significant improvement in progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced NSCLC regardless of tumor PD-L1 expression. Whole exome sequencing (WES) was performed to identify correlative biomarkers for survival. Methods: Patients (n = 465) with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomized 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) in combination with chemotherapy for 4-6 cycles, followed by maintenance of toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors included PD-L1 expression status, histology, and smoking status. The primary endpoint was PFS by investigator per RECIST v1.1. Secondary endpoints included PFS by a blinded independent review committee (BIRC), OS and safety. Results: At the prespecified final PFS analysis (cutoff date Oct 31, 2021), a significant improvement in PFS as assessed by investigator was observed for the toripalimab arm over the placebo arm: HR = 0.49 (95% CI: 0.39-0.61), two-sided p &lt; 0.0001, median PFS 8.4 vs 5.6 months. The 1-year PFS rates were 36.7% vs 17.2%. PFS as assessed by BIRC was also significantly longer in the toripalimab arm. The improvements of PFS were observed across key subgroups, including histology and PD-L1 expression. At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm: HR = 0.69 (95% CI: 0.52-0.92), two-sided p = 0.0099, median OS not reached vs 17.1 months. The incidence of Grade ≥3 adverse events (AEs) (78.6% vs 82.1%) was similar between the two arms. AEs leading to discontinuation of toripalimab/placebo (14.3% vs 3.2%) and fatal AEs (5.5% vs 2.6%) were more frequent in the toripalimab arm. WES results from 394 available patients revealed that patients with high tumor mutational burden (TMB) (≥10 mutations per million base pairs) were associated with significantly better PFS in the toripalimab arm over the placebo arm (median PFS 13.1 vs 5.5 months) (interaction P = 0.026). In addition, patients with mutations in the FAK-PI3K-Akt pathway or IL-7 signaling pathways achieved significantly better PFS and OS from the toripalimab chemotherapy combination (interaction P values ≤ 0.01). Conclusions: The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided superior PFS and OS when compared to chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as 1st line therapy for advanced NSCLC patients without EGFR/ALK mutations. Clinical trial information: NCT03856411.

362936 Background: Toripalimab (anti–PD-1) in combination with chemotherapy showed significant improvement in progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced non–small cell lung cancer (NSCLC) regardless of tumor PD-L1 expression. Whole-exome sequencing (WES) was performed to identify correlative biomarkers for survival. Methods: Patients (465 patients) with treatment-naïve, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (309 patients) or placebo (156 patients) in combination with chemotherapy for 4-6 cycles, followed by maintenance of toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors included PD-L1 expression status, histology, and smoking status. The primary endpoint was PFS by investigator per RECIST v1.1. Secondary endpoints included PFS by a blinded independent review committee (BIRC), OS, and safety. Results: At the prespecified final PFS analysis (cutoff date Oct 31, 2021), a significant improvement in PFS as assessed by investigator was observed for the toripalimab arm over the placebo arm: HR, 0.49 (95% CI, 0.39-0.61); two-sided p &lt; .0001; and median PFS 8.4 vs. 5.6 months. The 1-year PFS rates were 36.7% vs. 17.2%. PFS as assessed by BIRC was also significantly longer in the toripalimab arm. The improvements of PFS were observed across key subgroups, including histology and PD-L1 expression. At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm: HR, 0.69 (95% CI, 0.52-0.92); two-sided p = .0099; median OS not reached vs. 17.1 months. The incidence of grade ≥ 3 adverse events (AEs; 78.6% vs. 82.1%) was similar between the two arms. AEs leading to discontinuation of toripalimab/placebo (14.3% vs. 3.2%) and fatal AEs (5.5% vs. 2.6%) were more frequent in the toripalimab arm. WES results from 394 available patients revealed that patients with high tumor mutational burden (TMB; ≥ 10 mutations per million base pairs) were associated with significantly better PFS in the toripalimab arm over the placebo arm (median PFS 13.1 vs. 5.5 months; interaction p = .026). In addition, patients with mutations in the FAK-PI3K-Akt pathway or IL-7 signaling pathways achieved significantly better PFS and OS from the toripalimab chemotherapy combination (interaction p values ≤ .01). Conclusions: The addition of toripalimab to chemotherapy in patients with advanced NSCLC provided superior PFS and OS when compared to chemotherapy alone with a manageable safety profile. These results support the use of toripalimab with chemotherapy as first-line therapy for patients with advanced NSCLC without EGFR/ALK mutations. Clinical trial information: NCT03856411.

E2100, an open-label, randomized, phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG), demonstrated a significant improvement in progression-free survival (PFS) and overall response rate (ORR) with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer. An independent, blinded review of radiologic and clinical data was performed, assessing progression and response according to Response Evaluation Criteria in Solid Tumors. In addition, ECOG's investigator assessments were reanalyzed using the same methods applied to the independent review. The primary end point was PFS as assessed by an independent review facility (IRF). The addition of bevacizumab to paclitaxel resulted in a statistically significant improvement in PFS using both the IRF and investigator assessments. Hazard ratios for PFS (0.48, 95% CI, 0.385 to 0.607; P < .0001 for the IRF v 0.42, 95% CI, 0.34 to 0.52; P < .0001 for ECOG investigators) and the improvement in median PFS (11.3 v 5.8 months for the IRF v 11.4 v 5.8 months for ECOG investigators) were similar. Among patients with measurable disease at baseline, the IRF-assessed ORR was significantly higher in patients treated with paclitaxel and bevacizumab (48.9% v 22.2%; P < .0001). The risk of progression was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming a substantial and robust bevacizumab treatment effect. The consistency between the IRF and ECOG analyses validates the original data previously reported by ECOG in this open-label trial.

Background: Gemcitabine-Cisplatin (GP) chemotherapy is the standard first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, in combination with GP chemotherapy showed significant improvement in progression-free survival (PFS) as first-line treatment for RM-NPC at the interim analysis of the JUPITER-02 study (NCT03581786), a randomized, placebo-controlled, double-blinded international Phase III trial. Here we report the results of the final PFS analysis and the interim overall survival (OS) analysis. Methods: Patients (n=289) with advanced NPC with no prior chemotherapy in the recurrent or metastatic setting were randomized (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with gemcitabine and cisplatin every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo Q3W until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG PS (0 vs. 1) and extent of disease (recurrent vs. primary metastatic) at enrollment. Tumor response was assessed by a blinded independent review committee (BIRC) per RECIST v1.1. The primary endpoint was PFS by BIRC in the intention-to-treat population. Secondary end points included PFS by investigator, OS, objective response rate (ORR), duration of response (DOR) and safety. Results: At the final PFS analysis, the median follow-up time was 22.1 months for the toripalimab arm and 21.4 months for the placebo arm by the cut-off date of June 8, 2021. The toripalimab arm had a significantly longer PFS than the placebo arm as assessed by BIRC: median PFS 21.4 vs. 8.2 months, HR=0.52 (95% CI: 0.37-0.73), two-sided p&amp;lt;0.0001. The 1-year PFS rates were 59.0% vs. 32.9%. The ORR was 78.8% vs. 67.1% (P=0.022) and the median DOR was 18.0 vs. 6.0 months, HR= 0.49 (95% CI: 0.33-0.72). Consistently, PFS as assessed by investigator was also significantly longer in the toripalimab arm than the placebo arm: median PFS 17.3 vs. 8.1 months, HR=0.43 (95% CI: 0.31-0.58), P&amp;lt;0.0001. As of June 8, 2021, the median OS was not reached in either arm, with a trend favoring the toripalimab arm, HR=0.59 (95% CI: 0.37-0.94), P=0.024. The improvements of PFS and OS in the toripalimab arm were observed across key subgroups, including PD-L1 expression subgroups. Notably, dynamic decrease of plasma Epstein-Barr Virus DNA copy number from baseline was associated with favorable response. No new safety signal was identified. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (2.7% vs 2.8%) were similar between the two arms; however, investigator-determined immune-related AEs (irAEs) (53.4% vs. 21.7%) and Grade ≥3 irAEs (8.9% vs. 1.4%) were more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to GP chemotherapy as first-line treatment for advanced NPC had a manageable safety profile and provided superior PFS with a favorable trend in overall survival than chemotherapy alone. Citation Format: Hai-Qiang Mai, Qiu-Yan Chen, Dongping Chen, Chaosu Hu, Kunyu Yang, Jiyu Wen, Jingao Li, Yingrui Shi, Feng Jin, Ruilian Xu, Jianji Pan, Shenhong Qu, Ping Li, Chunhong Hu, Yi-Chun Liu, Yi Jiang, Xia He, Hung-Ming Wang, Wan-Teck Lim, Rui-Hua Xu, Coherus Biosciences and Shanghai Junshi Biosciences. Final progression-free survival analysis of JUPITER-02, a randomized, double-blind, phase 3 study of toripalimab or placebo plus gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT226.