Baseline circulating tumor cell (CTC) count as a prognostic marker of PSA response and progression in metastatic castrate sensitive prostate cancer (mCSPC): Results from SWOG S1216, a phase III randomized trial of androgen deprivation plus orteronel (cyp17 inhibitor) or bicalutamide.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5506-5506
Author(s):  
Amir Goldkorn ◽  
Catherine Tangen ◽  
Melissa Plets ◽  
Gareth Morrison ◽  
Alexander Cunha ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Circulating Tumor Cell ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Psa Response ◽  
Castrate Resistant ◽  
Hormonal Therapies

5506 Background: In mCSPC, androgen deprivation therapy (ADT) combined with chemotherapy or androgen receptor signaling inhibition (ARSI) is the new standard of care. Biomarkers that predict clinical outcomes with these therapies are needed. We hypothesized that CellSearch CTC count, an FDA-cleared biomarker in metastatic castrate resistant PC (mCRPC), may be a valuable biomarker in mCSPC. Methods: In S1216, peripheral blood was drawn with informed consent at registration (baseline), and CTCs were enumerated on the FDA-cleared CellSearch platform (Menarini) per standard manufacturer protocol. CTC counts were analyzed centrally for associations with 2 pre-specified trial intermediate endpoints: 7-month PSA (7mPSA) ≤ 0.2 ng/ml vs. 0.2–4.0 vs. > 4.0, (intermediate endpoint for overall survival, OS); and progression-free survival (PFS) < vs. > 2 years. Because OS data have not matured, analysis was pooled and equal numbers of samples were analyzed from each treatment arm and outcome measure (7mPSA and PFS) as stipulated by the Data Safety Monitoring Committee. Results: From 2014 to 2017, 523 baseline samples were collected. In the 7mPSA analysis (n = 264), CTCs were detected in 38% of men, with a median of 4 CTCs in those with detectable CTCs. In the PFS analysis (n = 336), CTCs were detected in 37% of men, with a median of 3 CTCs in those with detectable CTCs. Adjusting for disease burden (minimal vs. extensive) and ADT status (already initiated or not) at the time of CTC measurement, men with undetectable CTCs were 6.1-fold more likely to attain 7mPSA ≤ 0.2 (OR 6.1, 95% CI 2.1-17.2, p < 0.001) and 3.7-fold more likely to achieve > 2 years PFS (OR 3.7, 95% CI 1.7-8.1, p < 0.001) compared to men with baseline CTCs ≥ 5. Other cutpoints previously validated in mCRPC studies (CTC < 5 vs. ≥5 and CTCs 0 vs. ≥1) also strongly discriminated 7mPSA and PFS with statistical significance in this mCSPC cohort. Conclusions: CTC count at the start of treatment for mCSPC was highly prognostic of 7-month PSA response (intermediate endpoint for OS) and of PFS at 2 years. To our knowledge, this is the first such strong evidence from a prospective phase 3 trial of this magnitude. Additional analyses are planned when the trial is fully reported. Baseline CTC count may serve as a valuable prognostic marker to discriminate men likely to respond favorably to hormonal therapies from those who may benefit from early alternate interventions.

Phase II trial of abiraterone acetate (AA) treatment for metastatic prostate cancer (PC) patients with a PSA of more than four following initial androgen deprivation therapy: SWOG S1014.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 152-152
Author(s):  
Thomas W. Flaig ◽  
Catherine M. Tangen ◽  
Maha Hussain ◽  
Neeraj Agarwal ◽  
Nicholas Mitsiades ◽  
...  
Keyword(s):  
Androgen Deprivation Therapy ◽  
Poor Prognosis ◽  
Progression Free Survival ◽  
Poor Response ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Psa Response ◽  
Grade 3 ◽  
Hormonal Therapies

152 Background: Metastatic PC patients with a poor response to initial androgen deprivation therapy (ADT) as reflected by a PSA > 4 ng/ml after 7 months of ADT have a poor prognosis. In the S9346 trial, about 25% of all enrolled patients had a PSA > 4 ng/ml after 7 months of ADT with a subsequent median survival (OS) of 13 months. S1014 examined the efficacy of AA in this setting. Methods: Eligible patients with metastatic PC and a PSA of > 4ng/ml between 6-12 months after starting ADT were treated with 1,000 mg of AA daily + 5 mg of prednisone twice daily. PSA could be rising or falling at the time of enrollment, but had to be > 4 ng/ml. No chemotherapy or secondary hormonal therapies were allowed, except in patients receiving an anti-androgen at the time of enrollment, who were continued on this therapy. The primary endpoint was a PSA of ≤ 0.2ng/ml within 12 months of starting AA. The null hypothesis was a 5% rate and alternative was 20%, requiring 6 or more patients with PSA < 0.2 ng/ml to conclude the regimen is promising (one-sided α=0.048, power=0.92). Results: Forty-one patients were enrolled between 7/2012 and 7/2013. One patient was deemed not analyzable due to not receiving any protocol treatment. Fourteen patients remain on treatment. Five (13%) patients achieved an undetectable PSA of ≤ 0.2ng/ml (95% CI 4%, 27%). Nine (23%) additional patients had PSA level > 0.2 but < 4 ng/ml. Twenty-one patients had no PSA response and six were not assessable and assumed to be non-responders. The median progression-free survival (PFS) was 17.4 months. There was one incident each of Grade 4 ALT elevation and rectal bleeding. Twelve patients reported Grade 3 adverse events as their worst level of severity. Conclusions: Although encouraged by 5 patients attaining “undetectable” PSA responses to AA in this poor prognosis setting, this study did not reach the protocol pre-specified level of 6 responses. OS and PFS will be updated with further follow-up. The therapy was generally well tolerated, without any clear signal of any unexpected toxicity. Clinical trial information: NCT01309672.

SWOG S0421: Phase III study of docetaxel (D) and atrasentan (A) versus docetaxel and placebo (P) for men with advanced castrate resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4511-4511 ◽  
Author(s):  
David I. Quinn ◽  
Catherine M. Tangen ◽  
Maha Hussain ◽  
Primo Lara ◽  
Amir Goldkorn ◽  
...  
Keyword(s):  
Bone Markers ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Phase Iii ◽  
Endothelin Receptor ◽  
Free Survival ◽  
Primary Endpoints ◽  
Phase Iii Study ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

4511 Background: The endothelin pathway has a mechanistic role in bone metastases (mets). Atrasentan (A), an endothelin receptor antagonist, has reported activity in CRPC. This trial tested the survival impact of A + docetaxel (D) vs. D+ placebo (P) in CRPC pts with bone mets. Methods: Eligible CRPC pts, stratified for progression type, baseline pain index (BPI), extraskeletal mets and bisphosphonate (BisP) use, were randomized 1:1 to D+A vs. D+P for 12 3-wk cycles. Non-progressors could continue blinded drug alone for 16 more wks. Co-primary endpoints: overall (OS) and progression-free survival (PFS). 930 pts were needed to detect a 25% increase in med OS with D+A (1-sided log-rank, α=0.025, 87% power). Results: 991/1,038 pts were eligible: med age 69, 16% non-white, 61% on BisP, 31% prior prostatectomy, 42% worst pain by BPI ≥ 4, 20% PSA only progression and 56% extraskeletal mets. Multivariate analysis of baseline prognostic factors predicting worse OS were: measurable or evaluable disease progression, high BPI and extraskeletal mets (all p<0.02). No differences in median OS, PFS, or response between arms. Toxicities were similar between arms. Most common toxicities were fatigue, dyspnea, neutropenia and anemia. Addition of A trended to worse OS in pts with visceral mets (HR=1.13 p=0.21) and better OS in those without: bone only (HR=0.86, p=0.20). 357 pts continued A or P up to 52 weeks, no OS difference was seen post-chemo for this subset (p=0.92). Conclusions: This phase III study found no benefit for the addition of A to D in CRPC. Unless specific biomarkers can stratify a population for benefit, endothelin modulators have limited future use in advanced CRPC. Further analyses will test putative surrogacy effects of PSA, serum bone markers and circulating tumor cell kinetics for OS. [Table: see text]

scholarly journals Pain Progression at Initiation of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Post Hoc Analysis of the PROSELICA Study

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1284
Author(s):  
Nicolas Delanoy ◽  
Debbie Robbrecht ◽  
Mario Eisenberger ◽  
Oliver Sartor ◽  
Ronald de Wit ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radiological Progression ◽  
Post Hoc Analysis ◽  
Psa Response ◽  
Phase Iii Study ◽  
Psa Progression ◽  
Previously Treated ◽  
Post Hoc

Background: In the PROSELICA phase III trial (NCT01308580), cabazitaxel 20 mg/m2 (CABA20) was non-inferior to cabazitaxel 25 mg/m2 (CABA25) in mCRPC patients previously treated with docetaxel (DOC). The present post hoc analysis evaluates how the type of progression at randomization affected outcomes. Methods: Progression type at randomization was defined as follows: PSA progression only (PSA-p; no radiological progression (RADIO-p), no pain), RADIO-p (±PSA-p, no pain), or pain progression (PAIN-p, ±PSA-p, ±RADIO-p). Relationships between progression type and overall survival (OS), radiological progression-free survival (rPFS), and PSA response (confirmed PSA decrease ≥ 50%) were analyzed. Results: All randomized patients (n = 1200) had received prior DOC, and 25.7% had received prior abiraterone or enzalutamide. Progression type at randomization was evaluable in 1075 patients (PSA-p = 24.4%, RADIO-p = 20.8%, PAIN-p = 54.8%). Pain progression was associated with clinical and biological features of aggressive disease. Median OS from CABA initiation or date of mCRPC diagnosis, all arms combined, was shorter in the PAIN-p group than in the RADIO-p or the PSA-p groups (12.0 versus 16.8 and 18.4 months, respectively, p < 0.001). In multivariate analysis, all arms combined, PAIN-p was an independent predictor of poor OS (HR = 1.44, p < 0.001). PSA response, rPFS, and OS were numerically higher with CABA25 versus CABA20 in patients with PAIN-p. Conclusions: This post hoc analysis of the PROSELICA phase III study shows that pain progression at initiation of CABA in mCRPC patients previously treated with DOC is associated with a poor prognosis. Disease progression should be carefully monitored, even in the absence of PSA rise.

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.

scholarly journals Combined BRAF and MEK Inhibition with Vemurafenib and Cobimetinib for Patients with Advanced Melanoma

2017 ◽  
Vol 13 (01) ◽  
pp. 1
Author(s):  
Antonio M Grimaldi ◽  
Ester Simeone ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Paolo A Ascierto ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Combined Therapy ◽  
Acquired Resistance ◽  
Braf Inhibitor ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Mek Inhibition ◽  
Braf Mutant

Acquired resistance is the most common cause of BRAF inhibitor monotherapy treatment failure, with the majority of patients experiencing disease progression with a median progression-free survival of 6-8 months. As such, there has been considerable focus on combined therapy with dual BRAF and MEK inhibition as a means to improve outcomes compared with monotherapy. In the COMBI-d and COMBI-v trials, combined dabrafenib and trametinib was associated with significant improvements in outcomes compared with dabrafenib or vemurafenib monotherapy, in patients with BRAF-mutant metastatic melanoma. The combination of vemurafenib and cobimetinib has also been investigated. In the phase III CoBRIM study in patients with unresectable stage III-IV BRAF-mutant melanoma, treatment with vemurafenib and cobimetinib resulted in significantly longer progression-free survival and overall survival (OS) compared with vemurafenib alone. One-year OS was 74.5% in the vemurafenib and cobimetinib group and 63.8% in the vemurafenib group, while 2-year OS rates were 48.3% and 38.0%, respectively. The combination was also well tolerated, with a lower incidence of cutaneous squamous-cell carcinoma and keratoacanthoma compared with monotherapy. Dual inhibition of both MEK and BRAF appears to provide a more potent and durable anti-tumour effect than BRAF monotherapy, helping to prevent acquired resistance as well as decreasing adverse events related to BRAF inhibitor-induced activation of the MAPK-pathway. Combined BRAF and MEK inhibition is the standard of care in patients with advanced BRAF-mutant melanoma.

Radiographic progression-free survival as a surrogate endpoint of overall survival in men with metastatic castrate-resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5057-5057
Author(s):  
Susan Halabi ◽  
Akash Roy ◽  
Qian Yang ◽  
Wanling Xie ◽  
William Kevin Kelly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Phase Iii ◽  
Random Assignment ◽  
Moderate Correlation ◽  
Free Survival ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

5057 Background: Radiographic progression-free survival (rPFS) is commonly used as a co-primary endpoint in randomized clinical trials in men with metastatic castrate-resistant prostate cancer (mCRPC). However, rPFS has not been established as a valid surrogate endpoint of overall survival (OS) in men with mCRPC. Here, we hypothesized that rPFS is a reliable surrogate for OS in mCRPC. We also explored whether PFS is a valid surrogate endpoint of OS at the aggregate trial level. Methods: We performed a systematic search of the literature encompassing the period January 2004-December 2020 using PubMed and clinical trials.gov to identify completed phase III trials in mCRPC post-docetaxel. Eligible trials had to be randomized phase III therapeutic trials that reported OS, PFS or rPFS. OS was measured from the date of random assignment to date of death from any cause or date of last follow-up. rPFS was defined as the time from random assignment to date of disease progression on CT and/or Tc bone scan per trial definition or death from any cause, whichever occurred first. PFS included PSA progression as a component of the composite endpoint. Trial level surrogacy was evaluated by fitting linear regression on the treatment effect of rPFS (or PFS) and OS (in other words, the weighted linear regression of the log(hazard ratio) of OS on the log(hazard ratio) of rPFS). It was pre-specified that rPFS would be considered a valid surrogate for OS if R² was 0·7 or higher. Results: We identified 33 in men with mCRPC post docetaxel approval. We assessed the association between PFS and OS in 29,456 patients from 30 trials. Overall, a moderate correlation was observed at the trial level between OS and PFS ( R2 = 0.46, 95 %CI = 0.20-0.68) in these trials. In 18 trials with 16,818 mCRPC patients where rPFS was considered as a key endpoint, a moderate correlation between the treatment effects on rPFS and OS was observed at the trial level ( R2= 0.65, 95% CI = 0.23-0.87). Conclusions: This meta-analysis demonstrates moderate correlation between treatment effects of rPFS and OS in patients with mCRPC. However, rPFS did not meet the pre-specified surrogacy threshold of 0.7. Clinical trial information: several.

scholarly journals Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial

2018 ◽  
Vol 36 (31) ◽  
pp. 3077-3083 ◽  
Author(s):  
Lionnel Geoffrois ◽  
Laurent Martin ◽  
Dominique De Raucourt ◽  
Xu Shan Sun ◽  
Yungan Tao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival

Purpose Both concurrent chemoradiotherapy (CT-RT) and cetuximab radiotherapy (cetux-RT) have been established as the standard of care for the treatment of locally advanced squamous cell carcinoma of the head and neck. It was not known whether the addition of induction chemotherapy before cetux-RT could improve outcomes compared with standard of care CT-RT. Patients and Methods The current trial was restricted to patients with nonmetastatic N2b, N2c, or N3 squamous cell carcinoma of the head and neck and fit for taxotere, cisplatin, fluorouracil (TPF). Patients were randomly assigned to receive three cycles of TPF followed by cetux-RT versus concurrent carboplatin fluorouracil and RT as recommended in National Comprehensive Cancer Network guidelines. The trial was powered to detect a hazard ratio (HR) of 0.66 in favor of TPF plus cetux-RT for progression-free survival at 2 years. The inclusion of 180 patients per arm was needed to achieve 80% power at a two-sided significance level of .05. Results Between 2009 and 2013, 370 patients were included. All patients and tumors characteristics were well balanced between arms. There were more cases of grade 3 and 4 neutropenia in the induction arm, and the induction TPF was associated with 6.6% treatment-related deaths. With a median follow-up of 2.8 years, 2-year progression-free survival was not different between both arms (CT-RT, 0.38 v TPF + cetux-RT, 0.36; HR, 0.93 [95% CI, 0.73 to 1.20]; P = .58). HR was 0.98 (95% CI, 0.74 to 1.3; P = .90) for locoregional control and 1.12 (95% CI, 0.86 to 1.46; P = .39) for overall survival. These effects were observed regardless of p16 status. The rate of distant metastases was lower in the TPF arm (HR, 0.54 [95% CI, 0.30 to 0.99]; P = .05). Conclusion Induction TPF followed by cetux-RT did not improve outcomes compared with CT-RT in a population of patients with advanced cervical lymphadenopathy.

scholarly journals Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

2020 ◽  
Vol 38 (29) ◽  
pp. 3377-3387
Author(s):  
Pieternella Johanna Lugtenburg ◽  
Peter de Nully Brown ◽  
Bronno van der Holt ◽  
Francesco A. D’Amore ◽  
Harry R. Koene ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Intention To Treat ◽  
Large B Cell Lymphoma ◽  
Large B Cell

PURPOSE Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP. PATIENTS AND METHODS A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat. RESULTS CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections. CONCLUSION Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.

scholarly journals P14.15 Benefit of Bevacizumab for recurrent glioblastoma. Results of 81 patients from a single institution

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii69-iii69
Author(s):  
O Absalyamova ◽  
G Kobiakov ◽  
G Agabekyan ◽  
A Poddubsky ◽  
A Belyashova ◽  
...  
Keyword(s):  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
Phase Iii ◽  
Rapid Progression ◽  
Concomitant Disease ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Continuous Application

Abstract BACKGROUND No standard of care has been established for patients with progressive glioblastoma (rGBM). Previous studies suggested that bevacizumab (BEV) is safe and produces responses that result in a decreased use of glucocorticoids and increased progression-free survival (PFS) with an unclear effect on overall survival (OS). Crossover to BEV in the control arm is the possible reason why the advantage of BEV has not been proven in Phase III trials. We retrospectively analyzed own results of BEV treatment in rGBM. MATERIAL AND METHODS 81 patients progressed after radiotherapy plus concomitant and maintenance temozolomide (TMZ) and undergo BEV as monotherapy (BevMo, 11 patients) or in combinations (Irinotecan (BevI) - 53, lomustine (BevL)- 11, TMZ (BevT) - 6. Median age 54 years. Among them 33 patients were re-irradiated: 11 - radiosurgery (RS), 20 fractionated irradiation (RT), 2 - RS+RT. 33 patients continued BEV after progression with changing or adding cytostatic. PFS was calculated from the date of verification, PFS1 - from the date of 1-st progression, PFS2 - from the date of 2-nd progression. RESULTS Median PFS was 9.0 ([CI] 7.0–10.9) months. Median PFS1 was 10.5 ([CI] 8.1–12.9) months. In the BevMo, BevI, BevL, BevT group PFS1 was 15.7, 10.1, 10.5, 13.2 months, respectively, p=0.7. Objective response (OR) was reached in 34%, stable disease (SD) in 28%, progression (PD) in 37% patients. 16 patients stopped BEV without progression (4-patient`s decision, 7- doctor`s decision, 2 - adverse event, 3 - concomitant disease). Median time of BEV treatment was 11.6 months. Median BEV-free interval till progression was 3.7 months. 33 patients continued or restarted BEV after progression. Median PFS2 was 8.0 ([CI] 4.9–11.1) months. The median OS from the date of 1-st progression was 23.5 months ([CI] 18.7–27.4). In groups with RT, RS, RS+RT and no re-irradiarion OS was 24.6 ([CI] 17.6–31.5), 35.4 ([CI] 35.0–35.8), 17.8, 20.6 ([CI] 15.2–26.0), respectively, p=0.2. CONCLUSION OS in our group is outrageously high. Maintaining BEV after progression was effective. In our group BEV discontinuation led to rapid progression. The resumption of Bev with progression was effective, which indicates the advisability of its continuous application.

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

2020 ◽  
Vol 38 (3) ◽  
pp. 193-202 ◽  
Author(s):  
Richard S. Finn ◽  
Baek-Yeol Ryoo ◽  
Philippe Merle ◽  
Masatoshi Kudo ◽  
Mohamed Bouattour ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interim Analysis ◽  
Statistical Significance ◽  
Study Drug ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Double Blind ◽  
Previously Treated

PURPOSE Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.

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