Nomogram for predicting overall survival (OS) in patients (pts) treated with liposomal irinotecan (nal-IRI) ± 5-fluorouracil/leucovorin (5-FU/LV) in metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy in NAPOLI-1.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 459-459
Author(s):  
Andrea Wang-Gillam ◽  
Richard Hubner ◽  
Beloo Mirakhur ◽  
Floris A de Jong ◽  
Bruce Belanger ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Decision Making ◽  
Predictive Accuracy ◽  
Cox Model ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Relative Significance ◽  
Previously Treated

459 Background: Results from NAPOLI-1 (NCT01494506), a phase 3 study in pts with mPDAC previously treated with gemcitabine-based therapy, demonstrated an improvement in OS (primary endpoint), progression-free survival, and objective response rate with nal-IRI+5-FU/LV vs 5-FU/LV. The MPACT study reported a nomogram to predict OS using baseline pt variables in previously untreated mPDAC. We conducted an exploratory post hoc analysis of NAPOLI-1 variables to develop a nomogram to predict OS in the post-gemcitabine setting. Methods: In NAPOLI-1, pts were randomized to receive nal-IRI 80 mg/m2 q2w + 5-FU/LV, nal-IRI 100 mg/m2 q3w, or 5-FU/LV. Univariate and multivariate analyses determined factors significantly predictive of OS. A multivariable Cox model was created using these factors to develop a nomogram that assigned points equal to the weighted sum of relative significance of each variable. Predictive accuracy of the nomogram as measured by the concordance index (c-index) was evaluated by internal bootstrap validation. Results: Data from the 417-pt univariate analysis and 399-pt multivariate analysis (18 pts excluded for missing baseline data) were used. Eight of 21 variables were retained in the multivariate analysis (p < 0.01 except BMI [p=0.08]). Conclusions: In NAPOLI-1, predictors of OS were nal-IRI+5-FU/LV treatment, KPS, NLR, albumin level, baseline CA19-9, stage 4 at diagnosis, BMI, and presence of liver metastasis. The nomogram, which will distinguish between risk groups and may aid in clinical decision making, will be presented in the poster. Clinical trial information: NCT01494506. [Table: see text]

scholarly journals The Prognostic Value of Pre-treatment Hemoglobin (Hb) in Patients With Advanced or Metastatic Gastric Cancer Treated With Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Miaomiao Gou ◽  
Yong Zhang ◽  
Tiee Liu ◽  
Tongtong Qu ◽  
Haiyan Si ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Significant Prognostic Factor ◽  
Angiogenic Therapy ◽  
Pre Treatment

BackgroundBiomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC.MethodsWe retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level.ResultsWe included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001).ConclusionsOur study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.

Endometriumkarzinom: Kombination aus Lenvatinib und Pembrolizumab zeigt Wirksamkeit unabhängig vom Mikrosatellitenstatus

2021 ◽  
pp. 1-2
Author(s):  
Sarah Matz
Keyword(s):  
Endometrial Carcinoma ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy Analysis ◽  
Duration Of Response ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Prior Systemic Therapy ◽  
Grade 3

<b>Purpose:</b> Patients with advanced endometrial carcinoma have limited treatment options. We report final primary efficacy analysis results for a patient cohort with advanced endometrial carcinoma receiving lenvatinib plus pembrolizumab in an ongoing phase Ib/II study of selected solid tumors. <b>Methods:</b> Patients took lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks, in 3-week cycles. The primary end point was objective response rate (ORR) at 24 weeks (ORRWk24); secondary efficacy end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Tumor assessments were evaluated by investigators per immune-related RECIST. <b>Results:</b> At data cutoff, 108 patients with previously treated endometrial carcinoma were enrolled, with a median follow-up of 18.7 months. The ORRWk24 was 38.0% (95% CI, 28.8% to 47.8%). Among subgroups, the ORRWk24 (95% CI) was 63.6% (30.8% to 89.1%) in patients with microsatellite instability (MSI)-high tumors (n = 11) and 36.2% (26.5% to 46.7%) in patients with microsatellite-stable tumors (n = 94). For previously treated patients, regardless of tumor MSI status, the median DOR was 21.2 months (95% CI, 7.6 months to not estimable), median PFS was 7.4 months (95% CI, 5.3 to 8.7 months), and median OS was 16.7 months (15.0 months to not estimable). Grade 3 or 4 treatment-related adverse events occurred in 83/124 (66.9%) patients. <b>Conclusion:</b> Lenvatinib plus pembrolizumab showed promising antitumor activity in patients with advanced endometrial carcinoma who have experienced disease progression after prior systemic therapy, regardless of tumor MSI status. The combination therapy had a manageable toxicity profile. <b>Trial registration:</b> ClinicalTrials.gov NCT02501096.

AN INDIAN PROSPECTIVE STUDY OF DOCETAXEL THERAPY IN CRPC: CAN PRETREATMENT FACTORS PREDICT THE RESPONSE

2021 ◽  
pp. 78-81
Author(s):  
Devashish Kaushal ◽  
Rajeev Sood
Keyword(s):  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Multivariate Analysis ◽  
Gleason Score ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Carcinoma Prostate

Introduction: Studies on the effects of chemotherapy in Indian Castration-Resistant Prostate Cancer (CRPC) patients are very limited and world data is inconsistent. The purpose of the present study is to assess the effects of Docetaxel therapy in CRPC in Indian patients in terms of survival benet, both progression-free survival, and overall survival. This study also analyzes the effects of various factors on the survival of CRPC patients. Methodology: This is a single institutional prospective observational study. CRPC patients were treated with Docetaxel and followed till death as the primary endpoint or till the end of the study. Survivals were calculated with the Kaplan Meier method. Factors affecting survival were analyzed with univariate and multivariate analysis by log-rank t-test and Cox proportion hazard regression analysis. Result: Out of enrolled 101 patients, 78 were treated with Docetaxel. A decline in PSA (>50% reduction) was observed in 61.54%. Radiological response of regression noted in 40 % Nuclear Bone Scan and 19.23% CT/MRI by RECIST criteria. Progression-free survival and overall survival with Docetaxel (n=78) were 11.8 and 21 months respectively. Hemoglobin less than 11 gm%, Alkaline phosphatase more than 115 IU/dl, PSAmore than 14 ng/ml, Gleason score more than 7 and duration from diagnosis of carcinoma prostate to CRPC less than 24 months, the number of chemotherapy cycles less than 6 were all found to be signicantly associated with poor overall survival in univariate analysis while only Hemoglobin (P=0.0159) showed an independent association with overall survival in multivariate analysis. Conclusion: Overall and progression-free survival of CRPC patients with Docetaxel is 21 & 11.8 months respectively. Hemoglobin, Alkaline phosphatase, PSA, Gleason score, Docetaxel cycle, and duration from diagnosis of carcinoma prostate to CRPC were found to be signicantly associated with poor overall survival.

Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11516-11516
Author(s):  
Chang Gon Kim ◽  
Jin-Hee Ahn ◽  
Jeong Eun Kim ◽  
Jee Hung Kim ◽  
Min Kyung Jeon ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Alternative Hypothesis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Histologic Types

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m2 and gemcitabine 1,000 mg/m2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR12wks) with null and alternative hypothesis of PFSR12wks≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.

scholarly journals Impact of superselective intra-arterial and systemic chemoradiotherapy for gingival carcinoma; analysis of treatment outcomes and prognostic factors

2020 ◽  
Author(s):  
Yuki Mukai ◽  
Yuichiro Hayashi ◽  
Izumi Koike ◽  
Toshiyuki Koizumi ◽  
Madoka Sugiura ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Clinical Stage ◽  
Performance Status ◽  
Univariate Analysis ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Late Toxicity ◽  
Free Survival

Abstract Background: We compared outcomes and toxicities between concurrent retrograde super-selective intra-arterial chemoradiotherapy (IACRT) and concurrent systemic chemoradiotherapy (SCRT) for gingival carcinoma (GC).　Methods: We included 84 consecutive patients who were treated for non-metastatic GC ≥ stage III, from 2006 to 2018, in this retrospective analysis (IACRT group: n=66; SCRT group: n=18).Results: The median follow-up time was 24 (range: 1–124) months. The median prescribed dose was 60 (6–70.2) Gy (IACRT: 60 Gy; SCRT: 69 Gy). There were significant differences between the two groups in terms of 3-year overall survival (OS; IACRT: 78.8%, 95% confidence interval [CI]: 66.0–87.6; SCRT: 50.4%, 95% CI: 27.6–73.0; P = 0.039), progression-free survival (PFS; IACRT: 75.6%, 95% CI: 62.7–85.2; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.028) and local control rates (LC; IACRT: 77.2%, 95% CI: 64.2–86.4; SCRT: 42.0%, 95% CI: 17.7–70.9; P = 0.015). In univariate analysis, age ≥ 65 years, decreased performance status (PS) and SCRT were significantly associated with worse outcomes (P < 0.05). In multivariate analysis, age ≥ 65 years, clinical stage IV, and SCRT were significantly correlated with a poor OS rate (P < 0.05). Patients with poorer PS had a significantly worse PFS rate. Regarding acute toxicity, 22 IACRT patients had grade 4 lymphopenia, and osteoradionecrosis was the most common late toxicity in both groups.Conclusions: This is the first report to compare outcomes from IACRT and SCRT among patients with GC. ALL therapy related toxicities were manageable. IACRT is an effective and safe treatment for GC.

VAD-PECC regimen in the treatment of advanced-stage multiple myeloma.

1994 ◽  
Vol 12 (12) ◽  
pp. 2706-2713 ◽  
Author(s):  
M Delain ◽  
C Linassier ◽  
C Petitdidier ◽  
P Goupille ◽  
F Luthier ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Response ◽  
Response Rate ◽  
Cox Model ◽  
Univariate Analysis ◽  
Karnofsky Score ◽  
Term Survival ◽  
Baseline Serum ◽  
Previously Treated Patients ◽  
Previously Treated

PURPOSE This prospective study was undertaken to evaluate the efficacy of combination chemotherapy with alternating cycles of vincristine, doxorubicin, and dexamethasone (VAD) and prednisone, vindesine, carmustine, and cyclophosphamide (PECC) in poor-risk multiple myeloma (MM). PATIENTS AND METHODS Forty-four patients were previously untreated; 36 had been pretreated with an alkylating agent-containing regimen and had refractory or relapsed MM. All previously untreated patients had a high tumor burden at inclusion (stage III according to the Durie and Salmon classification). Logistic regression and the Cox proportional hazards models were used to assess the association between patient characteristics and response rate and survival, respectively. RESULTS The overall response rate was 68% for previously untreated patients, compared with 54% for previously treated patients (P = .16). The median survival time for all patients was 28 months: 53 months in previously untreated patients, and 18 months in previously treated patients. Univariate analysis showed that the predictive factors that had a significant affect on survival in the newly diagnosed patients were age, therapeutic response to VAD-PECC, low pretreatment Karnofsky score, high baseline serum beta 2-microglobulin (beta 2M) level, bone marrow impairment, and renal insufficiency at the start of treatment. When these parameters were used as continuous variables in multivariate analysis, three were found to correlate with survival: serum beta 2M, followed by therapeutic response and Karnofsky score. In the previously treated group, only Karnofsky score entered the Cox model. CONCLUSION These results indicate that combination VAD-PECC chemotherapy is an effective treatment that results in high response rates and long-term survival in advanced MM.

Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology

2003 ◽  
Vol 21 (24) ◽  
pp. 4572-4578 ◽  
Author(s):  
Véronique Laithier ◽  
Jacques Grill ◽  
Marie-Cécile Le Deley ◽  
Marie-Madeleine Ruchoux ◽  
Dominique Couanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optic Pathway ◽  
Free Survival ◽  
Factors Associated ◽  
Response To Chemotherapy ◽  
Risk Of Disease

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

Regression Does Not Predict Nodal Metastasis or Survival in Patients with Cutaneous Melanoma

2011 ◽  
Vol 77 (8) ◽  
pp. 1009-1013 ◽  
Author(s):  
Alison L. Burton ◽  
Juliana Gilbert ◽  
Russell W. Farmer ◽  
Arnold J. Stromberg ◽  
Lee Hagendoorn ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cutaneous Melanoma ◽  
Clinical Decision Making ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Nodal Metastasis ◽  
Breslow Thickness ◽  
Significant Prognostic Factor ◽  
Superficial Spreading ◽  
Histologic Subtype

Controversy exists regarding the prognostic implications of regression in patients with cutaneous melanoma. Some consider regression to be an indication for sentinel lymph node (SLN) biopsy because regression may result in underestimation of the true Breslow thickness. Other data support regression as a favorable prognostic indicator, representing immune system recognition of the primary tumor. This analysis was performed to determine whether regression predicts nodal metastasis, disease-free survival (DFS), or overall survival (OS). Post hoc analysis was performed of a multicenter prospective randomized trial that included patients aged 18 to 70 years with cutaneous melanomas 1 mm or greater Breslow thickness. All patients underwent SLN biopsy; those with tumor-positive SLN underwent completion lymphadenectomy. Kaplan-Meier analysis of survival, univariate analysis, and multivariate analysis were performed. A total of 2220 patients (261 with regression; 1959 without regression) were included in this analysis with a median follow-up of 68 months. Patients with regression were more likely to be male, older than 50 years old, and have lower median Breslow thickness, superficial spreading histologic subtype, and a non-extremity anatomic location ( P < 0.05 in all cases). Regression was not significantly associated with Clark level, ulceration, lymphovascular invasion, number of SLNs removed, or SLN metastasis. On multivariate analysis, factors independently predictive of DFS included Breslow thickness, ulceration, and SLN status ( P < 0.05 in all cases); the same factors along with age, gender, and anatomic tumor location were significantly associated with OS ( P < 0.05 in all cases). Regression was not significantly associated with DFS (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.67-1.27; P = 0.68) or OS (RR, 1.01; 95% CI, 0.76-1.32; P = 0.93). These data suggest that regression is not a significant prognostic factor for patients with cutaneous melanoma and should not be used to guide clinical decision-making for such patients.

Vinorelbine Is an Effective and Safe Drug for AIDS-Related Kaposi’s Sarcoma: Results of a Phase II Study

2000 ◽  
Vol 18 (7) ◽  
pp. 1550-1557 ◽  
Author(s):  
Guglielmo Nasti ◽  
Domenico Errante ◽  
Renato Talamini ◽  
Giuliano Rizzardini ◽  
Marco Fasan ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Objective Response ◽  
Kaposi’S Sarcoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Duration Of Response ◽  
Previously Treated ◽  
Chemotherapy Patients ◽  
Dose Limiting Toxicity

PURPOSE: To assess the safety and efficacy of vinorelbine in patients with AIDS-related Kaposi’s sarcoma (KS). PATIENTS AND METHODS: From December 1994 to May 1997, within the Italian Cooperative Group on AIDS and Tumors, we enrolled 36 patients with AIDS-related KS who experienced disease progression after one or more regimens of systemic chemotherapy. Patients were treated with vinorelbine 30 mg/m2 every 2 weeks by intravenous bolus. RESULTS: Of 35 assessable patients, three (9%) had a clinical complete response and 12 (34%) had a partial remission, for an overall objective response rate of 43% (95% confidence interval, 26% to 61%). For the 15 patients with objective responses, the median duration of response from the beginning of therapy until the development of progression was 176 days, whereas the median progression-free survival and the median survival durations for 35 assessable patients were 151 days and 216 days, respectively. Vinorelbine also induced responses in patients who had become resistant to regimens that included other vinca alkaloids. Overall, vinorelbine was well tolerated. Toxicity, including neurologic toxicity, was mild and reversible. Neutropenia was the most frequent dose-limiting toxicity. CONCLUSION: Vinorelbine is safe and effective in the treatment of patients with advanced KS who have been previously treated with one or more chemotherapy regimens.

HALO 202: Randomized Phase II Study of PEGPH20 Plus Nab-Paclitaxel/Gemcitabine Versus Nab-Paclitaxel/Gemcitabine in Patients With Untreated, Metastatic Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 36 (4) ◽  
pp. 359-366 ◽  
Author(s):  
Sunil R. Hingorani ◽  
Lei Zheng ◽  
Andrea J. Bullock ◽  
Tara E. Seery ◽  
William P. Harris ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response Rate ◽  
Response Rate ◽  
Event Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
End Points ◽  
Grade 3

Purpose Metastatic pancreatic ductal adenocarcinoma is characterized by excessive hyaluronan (HA) accumulation in the tumor microenvironment, elevating interstitial pressure and impairing perfusion. Preclinical studies demonstrated pegvorhyaluronidase alfa (PEGPH20) degrades HA, thereby increasing drug delivery. Patients and Methods Patients with previously untreated metastatic pancreatic ductal adenocarcinoma were randomly assigned to treatment with PEGPH20 plus nab-paclitaxel/gemcitabine (PAG) or nab-paclitaxel/gemcitabine (AG). Tumor HA levels were measured retrospectively using a novel affinity histochemistry assay. Primary end points were progression-free survival (PFS; overall) and thromboembolic (TE) event rate. Secondary end points included overall survival, PFS by HA level, and objective response rate. An early imbalance in TE events in the PAG arm led to a clinical hold; thereafter, patients with TE events were excluded and enoxaparin prophylaxis was initiated. Results A total of 279 patients were randomly assigned; 246 had HA data; 231 were evaluable for efficacy; 84 (34%) had HA-high tumors (ie, extracellular matrix HA staining ≥ 50% of tumor surface at any intensity). PFS was significantly improved with PAG treatment overall (hazard ratio [HR], 0.73; 95% CI, 0.53 to 1.00; P = .049) and for patients with HA-high tumors (HR, 0.51; 95% CI, 0.26 to 1.00; P = .048). In patients with HA-high tumors (PAG v AG), the objective response rate was 45% versus 31%, and median overall survival was 11.5 versus 8.5 months (HR, 0.96; 95% CI, 0.57 to 1.61). The most common treatment-related grade 3/4 adverse events with significant differences between arms (PAG v AG) included muscle spasms (13% v 1%), neutropenia (29% v 18%), and myalgia (5% v 0%). TE events were comparable after enoxaparin initiation (14% PAG v 10% AG). Conclusion This study met its primary end points of PFS and TE event rate. The largest improvement in PFS was observed in patients with HA-high tumors who received PAG. A similar TE event rate was observed between the treatment groups in stage 2 of the trial.

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