TAS-102 versus placebo (PBO) in patients (pts) ≥65 years (y) with metastatic colorectal cancer (mCRC): An age-based analysis of the recourse trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 638-638 ◽  
Author(s):  
Eric Van Cutsem ◽  
Fabio M. Benedetti ◽  
Hirokazu Mizuguchi ◽  
Robert J. Mayer ◽  
Alfredo Falcone ◽  
...  
Keyword(s):  
Safety Profile ◽  
Drug Exposure ◽  
Weight Ratio ◽  
Progression Free Survival ◽  
Molar Ratio ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Age Related ◽  
Grade 3 ◽  
Favorable Safety

638 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil hydrochloride, at a molar ratio of 1:0.5 (weight ratio, 1:0.471). Efficacy and safety of TAS-102 in pts with mCRC refractory to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥2 prior lines of standard chemotherapy. Primary results of RECOURSE demonstrated a significant improvement in overall survival (OS) (TAS-102 7.1 mo vs PBO 5.3 mo; HR=0.68; P<0.0001) and progression-free survival (PFS) (HR=0.48; P<0.0001). Methods: This prespecified analysis compared the efficacy and safety of TAS-102 vs PBO in pts ≥65 y and <65 y with mCRC. A retrospective analysis of pts ≥75 y was also performed. Results: Of 800 randomized pts, 352 (44.0%) were ≥65 y and 60 (7.5%) were ≥75 y. Median OS in pts ≥65 y was 7.0 mo with TAS-102 vs 4.6 mo with PBO (HR=0.62, 95% CI: 0.48-0.80, P=0.0002). PFS HR was 0.41 (95% CI: 0.32-0.52, P<0.0001) for pts ≥65 y, also favoring TAS-102. In pts ≥65 y, disease control rate (complete or partial response or stable disease) was 48.7% with TAS-102 vs 15.5% with PBO. An age-related difference in overall incidence of adverse events (AEs) was not observed in either treatment arm. Treatment-related AEs, ≥ Grade 3 AEs, and severe AEs were generally more common in pts ≥65 y than in pts <65 y (Table). Mean drug exposure was similar among pts ≥65 y and ≥75 y, as was overall safety profile. Conclusions: Significant improvements in OS and PFS were observed in pts ≥65 y who received TAS-102 vs PBO, with a mild increase in toxicity. Pts ≥65 y and <65 y showed a generally favorable safety profile. A significant increase in toxicity in pts ≥75 y was not apparent vs the overall ≥65 y population. Clinical trial information: NCT01607957. [Table: see text]

Phase III RECOURSE trial of TAS-102 versus placebo with best supportive care in patients with metastatic colorectal cancer: Geographic subgroups.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 646-646 ◽  
Author(s):  
Atsushi Ohtsu ◽  
Takayuki Yoshino ◽  
Mona M. Wahba ◽  
Fabio M. Benedetti ◽  
Alfredo Falcone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Weight Ratio ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Molar Ratio ◽  
Efficacy And Safety ◽  
The Us ◽  
Grade 3

646 Background: TAS-102 is comprised of an antineoplastic thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil hydrochloride, at a molar ratio of 1:0.5 (weight ratio, 1:0.471). The efficacy and safety of TAS-102 in patients (pts) with metastatic colorectal cancer refractory/intolerant to standard therapies were evaluated in the RECOURSE trial; enrollment criteria included ≥ 2 prior lines of standard chemotherapy. Primary results of RECOURSE demonstrated a significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 vs placebo (PBO) (hazard ratio [HR] = 0.68 and 0.48 for OS and PFS, respectively; both P< 0.0001). Methods: RECOURSE data were evaluated for efficacy and safety, including rate of hospitalizations, of TAS-102 vs PBO by each geographic subgroup of US, EU, and Japan (JP). Results: Of 768 pts, 99 US (mean age, 60 y), 403 EU (mean age, 62 y), and 266 JP (mean age, 62 y) pts were randomized to receive TAS-102 or PBO. Median OS with TAS-102 vs PBO was 6.5 mo vs 4.3 mo in US pts, 6.8 mo vs 4.9 mo in EU pts, and 7.8 mo vs 6.7 mo in JP pts. HRs for OS and PFS for US, EU, and JP pts all favored TAS-102 (Table). There were no marked differences among the US, EU, and JP subgroups with respect to overall incidence of adverse events (AEs), ≥ Grade 3 AEs, serious AEs (SAEs), or hospitalizations. Conclusions: Similar to the overall RECOURSE population, OS and PFS benefits were observed in each geographic subgroup randomized to TAS-102 vs PBO, with an acceptable safety profile. Clinical trial information: NCT01607957. [Table: see text] [Table: see text]

Efficacy and safety of weekly paclitaxel in elderly patients with heavily pretreated platinum-resistant ovarian carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17552-e17552
Author(s):  
Rodrigo Sanchez-Bayona ◽  
Pablo Tolosa ◽  
Ana Sanchez de Torre ◽  
Alicia Castelo ◽  
Elsa Bernal-Hertfelder ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Ovarian Carcinoma ◽  
Progression Free Survival ◽  
High Grade ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Serous Ovarian Carcinoma ◽  
Platinum Resistant ◽  
Heavily Pretreated ◽  
Grade 3

e17552 Background: In platinum-resistant ovarian cancer treatment, single-agent paclitaxel can be used alone or in combination with bevacizumab. We aimed to assess the efficacy and safety profile of a weekly paclitaxel (WP) scheme in heavily pretreated platinum-resistant high-grade serous ovarian carcinoma. Methods: We retrospectively analyzed 30 adult patients with platinum-resistant high-grade serous ovarian carcinoma treated with WP at our institution between 2015 and 2020. Patients with platinum-resistant ovarian, fallopian tube or primary carcinoma of the peritoneum who had received at least 3 doses of WP (80 mg/m2) alone or in combination with bevacizumab until disease progression or unacceptable toxicity were included in the analysis. Progression-free survival was assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Information about toxicity was gathered from medical reports and lab tests. Kaplan-Meier curves and Log-rank test were performed for survival estimates. Results: In our sample, the median age was 68 years (IQR: 60-75) and the median number of previous lines of systemic treatment was 3 (range 1-5). 40% of patients received WP in combination with bevacizumab. The disease control rate was 60.7% (42.9% partial response and 17.8% stable disease). In the overall analysis, the median progression-free survival (mPFS) was 5.0 months (95% CI: 2.0-7.1 months). The presence of ascites significantly shortened the mPFS compared to patients without it (1.1 vs 5.1 months, p < 0.001). Even though the addition of bevacizumab to WP improved the mPFS, the difference was not statistically significant compared to WP alone (7.1 vs 4.06 months, p=0.30). Peripheral neuropathy was the most common adverse event (78% all grades, 18% grade 3). No grade 3 hematologic toxicity was registered. Treatment was discontinued in 6 patients (20%) – 4 due to peripheral neuropathy and two because of toxicoderma. Conclusions: In our sample, WP was an active and safe regimen in heavily pretreated platinum-resistant ovarian carcinoma. WP was well tolerated in elderly patients. The presence of ascites was associated to a shorter PFS in patients treated with WP compared to ascites-free patients.

scholarly journals Combining Correlated Outcomes and Surrogate Endpoints in a Network Meta-Analysis of Colorectal Cancer Treatments

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2663
Author(s):  
Tung Hoang ◽  
Jeongseon Kim
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Cancer Treatments ◽  
Free Survival ◽  
Hazard Ratios ◽  
Credible Intervals ◽  
Grade 3 ◽  
Selection Of

This study aimed to investigate the efficacy and safety of systemic therapies in the treatment of unresectable advanced or metastatic colorectal cancer. Predicted hazard ratios (HRs) and their 95% credible intervals (CrIs) for overall survival (OS) were calculated from the odds ratio (OR) for the overall response rate and/or HR for progression-free survival using multivariate random effects (MVRE) models. We performed a network meta-analysis (NMA) of 49 articles to compare the efficacy and safety of FOLFOX/FOLFIRI±bevacizumab (Bmab)/cetuximab (Cmab)/panitumumab (Pmab), and FOLFOXIRI/CAPEOX±Bmab. The NMA showed significant OS improvement with FOLFOX, FOLFOX+Cmab, and FOLFIRI+Cmab compared with that of FOLFIRI (HR = 0.84, 95% CrI = 0.73–0.98; HR = 0.76, 95% CrI = 0.62–0.94; HR = 0.80, 95% CrI = 0.66–0.96, respectively), as well as with FOLFOX+Cmab and FOLFIRI+Cmab compared with that of FOLFOXIRI (HR = 0.69, 95% CrI = 0.51–0.94 and HR = 0.73, 95% CrI = 0.54–0.97, respectively). The odds of adverse events grade ≥3 were significantly higher for FOLFOX+Cmab vs. FOLFIRI+Bmab (OR = 2.34, 95% CrI = 1.01–4.66). Higher odds of events were observed for FOLFIRI+Pmab in comparison with FOLFIRI (OR = 2.16, 95% CrI = 1.09–3.84) and FOLFIRI+Bmab (OR = 3.14, 95% CrI = 1.51–5.89). FOLFOX+Cmab and FOLFIRI+Bmab showed high probabilities of being first- and second-line treatments in terms of the efficacy and safety, respectively. The findings of the efficacy and safety comparisons may support the selection of appropriate treatments in clinical practice. PROSPERO registration: CRD42020153640.

scholarly journals A multicenter phase II study of Q3 week or weekly paclitaxel in combination with bevacizumab for the treatment of metastatic or unresectable angiosarcoma

Rare Tumors ◽  
2018 ◽  
Vol 10 ◽  
pp. 203636131877177 ◽  
Author(s):  
Nam Bui ◽  
Nikhil Kamat ◽  
Vinod Ravi ◽  
Sant Chawla ◽  
Marti Lohman ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Progression Free Survival ◽  
Weekly Paclitaxel ◽  
Comparable Efficacy ◽  
Progression Rate ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Multicenter Phase ◽  
Grade 3 ◽  
To Receive

Paclitaxel (P) and bevacizumab (B) are agents that provide clinical benefit in advanced angiosarcoma (AS). The objective of this study was to assess the efficacy and safety of P-B in two different scheduled regimens. Patients were to receive P 200mg/m2 IV with B 15mg/kg IV every 21 days (Regimen A) or P 90mg/m2 IV weekly D1, 8, 15 with B 15mg/kg IV D1 of a 28 day cycle (Regimen B) x6 cycles. Maintenance B followed at a dose of 15 mg/kg intravenously once every 21 days. The primary end point was 4 month non-progression rate (NPR). A total of 16 patients were enrolled. 4 month NPR was 62.5% with median overall survival 16 months and median progression free survival 5.06 months. 11 patients made it to cycle 3 and were evaluable for response with 1 CR (9%), 4 PR (36%), 2 SD (18%), and 6 PD (36%). There were ten grade 3 toxicities and four grade 4 toxicities. The breakdown between the two regimens revealed comparable efficacy and safety. Paclitaxel and Bevacizumab is an active regimen in angiosarcoma. Q3 week and weekly paclitaxel appear similar in efficacy and safety.

scholarly journals Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Adverse Events ◽  
Subcutaneous Administration ◽  
Progression Free Survival ◽  
The Other ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

Age-related efficacy and safety of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in subgroups of patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Post hoc analysis of SPARTAN.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5024-5024 ◽  
Author(s):  
Julie Nicole Graff ◽  
Matthew Raymond Smith ◽  
Fred Saad ◽  
Boris A. Hadaschik ◽  
Hiroji Uemura ◽  
...  
Keyword(s):  
High Risk ◽  
Safety Profile ◽  
Age Groups ◽  
Progression Free Survival ◽  
Controlled Study ◽  
Castration Resistant Prostate Cancer ◽  
Cox Models ◽  
Free Survival ◽  
Age Related ◽  
The Impact

5024 Background: SPARTAN, a randomized phase 3 placebo (PBO)-controlled study in pts with high-risk nmCRPC and PSA doubling time ≤ 10 mo, showed that, compared with PBO, addition of APA to ongoing ADT treatment (tx) prolonged metastasis-free survival (MFS) by > 2 y, reduced the risk of symptomatic progression by 55%, and increased second progression-free survival (PFS2), which is the time from randomization to disease progression on first subsequent anticancer tx, or death. The impact of APA in terms of benefit and safety profile was evaluated in pts aged < 65, 65-74, and ≥ 75 y. Methods: Pts with nmCRPC were randomized 2:1 to APA (240 mg QD) or PBO; ADT was continuous. APA effect was analyzed by Cox models and Kaplan-Meier methods across age subgroups. Results: Baseline characteristics among age groups were similar, although ECOG PS 1 vs 0 increased with age. MFS benefit with APA was highly significant for all age subgroups (Table). In pts ≥ 75 y, MFS risk with APA vs PBO was reduced by 59%; MFS risk was reduced by 86% and 76% for pts < 65 and 65-74 y, respectively. Risk of PFS2 with APA vs PBO was reduced across all age subgroups. PFS2 in pts < 65, 65-74, and ≥ 75 y: HR, 0.09 (p < 0.0001); HR, 0.56 (p = 0.0343); HR, 0.59 (p = 0.0092), respectively. Risk of symptomatic progression was lessened with APA vs PBO for all age subgroups (Table). There was a similar increase in incidence of tx-emergent adverse events (TEAE) with age in both tx arms that remained higher with APA. Incidence of grade 3/4 TEAE (≥ 75 vs < 65 y): APA, 50% vs 37%; PBO, 37% vs 28%. Conclusions: Pts in all age subgroups with high-risk nmCRPC had significant improvement in MFS with APA + ongoing ADT. The safety profile of APA was similar across age subgroups. Clinical trial information: NCT01946204. [Table: see text]

Low-dose cisplatin administration through the superficial temporal artery combined with definitive radiotherapy for maxillary sinus squamous cell carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18562-e18562
Author(s):  
Tatsuo Masubuchi ◽  
Yosuke Kitani ◽  
Chihiro Fushimi ◽  
Daisuke Kawakita ◽  
Hideaki Takahashi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Low Dose ◽  
Superficial Temporal Artery ◽  
Progression Free Survival ◽  
Temporal Artery ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Grade 3

e18562 Background: Although patients with locoregional advanced maxillary sinus squamous cell carcinoma (MSSCC) are often treated with surgery followed by postoperative radiotherapy (RT), the cosmetic and functional outcomes are unsatisfactory. Moreover, the efficacy and safety of intra-arterial chemoradiotherapy are controversial. Methods: In this study, we investigated the efficacy and safety of low-dose cisplatin administration through the superficial temporal artery (STA) combined with definitive RT in patients with MSSCC. Between January 2009 and December 2018, 57 patients were administered weekly intra-arterial infusions of cisplatin (30–50 mg/m2/5h) through the STA with simultaneous intravenous infusions of sodium thiosulfate. Overall response rate (ORR), local progression-free survival (LFS), maxillectomy-free survival (MFS), progression-free survival (PFS), overall survival (OS), and safety were evaluated retrospectively. The impact of clinical factors on survival was investigated using the Cox proportional hazard models. Results: The median follow-up time was 44 months (range, 10–80 months). There were 4, 26, 23, and 4 patients with cT2, cT3, cT4a, and cT4b, respectively. All patients completed the planned treatment except for one patient who discontinued owing to facial palsy. The ORR was 98% with 51 and 5 patients having complete and partial responses, respectively. The 3-year LFS, PFS, and OS were 74%, 63%, and 81%, respectively for all patients and 100%, 81%, and 94%, respectively for 22 patients received 70 Gy irradiation. Notably, the 3-year MFS was 95% for all patients and 100% in patients received 70 Gy RT. The most common grade 3 or more toxic event was oral mucositis (22.8%). Additionally, 4 (7.0%) patients had catheter-related infections. Late grade 3 or more adverse events included optic nerve disorder (8.8%), osteonecrosis (7.0%), encephalopathy (1.8%), and increased creatinine levels (1.8%). Salvage surgery including hard palate resection and orbital exenteration were performed in 2 and 1 patients, respectively. No clinical factor was correlated with survival outcomes in our study cohort. Conclusions: Low-dose cisplatin through STA combined with RT, especially 70 Gy RT, was associated with promising tumor response, high organ preservation rate, and tolerable adverse events in MSSCC patients. Further prospective studies are warranted to compare these outcomes with primary surgery.

A hypothesis-generating exploratory analysis of efficacy and safety of abiraterone acetate (AA) in African American (Af Am) patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 55-55
Author(s):  
Eleni Efstathiou ◽  
Vasily J. Assikis ◽  
Scott A. North ◽  
John Showel ◽  
Thomas E. Hutson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Profile ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Psa Response ◽  
Grade 3

55 Background: The reported increased prostate cancer lethality in Af Ams has been attributed by some to altered androgen receptor (AR) signaling. We compared toxicity, PSA response, time-to-PSA progression (TTPP), and radiographic progression-free survival (rPFS) in Af Am vs non Af Am pts with CRPC treated with AA + prednisone (P) vs placebo + P. We hypothesized that differences in response to AA may be observed if differences in AR signaling exist in Af Ams. Methods: COU-AA-301 is a randomized double blind study of AA (1000 mg + P 5 mg po BID) vs placebo + P post-docetaxel. Results: TTPP, rPFS, and PSA response rate were higher with AA vs placebo. In Af Am pts, treatment emergent AEs (TEAEs) for AA vs placebo occurred in 96.4% vs 100.0% of pts (50.0% and 66.7%, respectively, grade 3/4); serious TEAEs occurred in 42.9% and 33.3% of pts (28.6% and 26.7%, respectively, grade 3/4). The safety profile of AA appears comparable between the Af Am and overall study populations. Conclusions: Although the small number of Af Am pts in this study precludes formal conclusions regarding efficacy and safety of AA in this pt population, the overall trend suggests these pts experienced clinical benefit from AA with a safety profile comparable to the overall study population. These findings do not appear to support the hypothesis that AR signaling accounts for the increased lethality of prostate cancer seen in Af Ams. Further studies of AA in Af Am pts are planned to understand the potential benefit in this population. Additional efforts are needed to increase participation of Af Am pts in clinical trials. [Table: see text]

Clinical efficacy and safety of proton beam or photon radiation in combination with immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16113-e16113
Author(s):  
Chung Wei Su ◽  
Pei-Wei Huang ◽  
Yung-Chih Chou ◽  
Chen-Chun Lin ◽  
Ji-Hong Hong ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Photon Radiation ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Proton Group ◽  
Free Survival ◽  
Grade 3

e16113 Background: Management of advanced hepatocellular carcinoma (HCC) remains a challenge. IMbrave150, a pivotal trial reported impressive overall survival benefit using combination strategy of atezolizumab and bevacizumab compared to sorafenib. We wonder the efficacy and safety when combining radiotherapy with immune checkpoint inhibitors (ICIs), which radiation might provide better local treatment and possible trigger abscopal effect. The aim of this study is retrospectively reporting the real-world efficacy and tolerability of proton beam or photon radiation plus ICIs in patients with advance stage HCC. Methods: We retrospectively reviewed all BCLC stage C HCC patients who have received combination therapy with ICIs plus proton or photon therapy with well documented basic characteristics and prompt treatment efficacy evaluation between 1st of January 2016 to 31st of October 2019 at a single medical center in Taiwan. 20 patients had ICIs plus proton and 32 patients had ICIs plus photon were included for analysis. Overall survival (OS) and progression free survival (PFS) were evaluated by Kaplan-Meier estimator. Results: Baseline characteristics were generally similar between ICIs plus proton or ICIs plus photon, while most patients in proton group did not receive prior systemic treatment and had less local therapies prior ICIs combine with radiotherapy. Median follow-up time was 10.7 months. The median Progression free survival (PFS) was not reached in ICIs plus proton group and 3.6 months (95% CI 2.7-4.6) in ICIs plus photon group (P = 0.007). The median OS was not reach in ICIs plus proton group and 12.1months (95% CI 6.4-17.7) in ICIs plus photon group (P = 0.007). Comparing ICIs plus proton group versus photon group, objective tumor response is 50% versus 9%, disease control rate is 80% versus 47% in each group. During follow-up, 7 patients (35%) in proton group achieved complete remission (CR). There was difference in radiation filed, 19 patients (95%) in proton group and 15 patients (47%) in photon group targeted on liver tumors, and more patient received > 50Gy treatment dose in proton group compared to photon group (90% versus 20%). Proton group has lower failure rate in both inner- or out-field compared to photon group. Grade 1 to grade 2 skin-dermatological and gastrointestinal toxicity remained the most frequent reported adverse events in both groups. There are only one therapy related grade 3 dermatitis in ICIs plus proton group and one grade 3 hepatitis, one grade 5 pneumonitis in ICIs plus photon group. Conclusions: This study reported real-world efficacy and safety of ICIs in combination with proton or photon therapy. Most adverse events were manageable. The combination of ICIs and proton therapy has impressive CR rate and OS benefit. Further prospective randomized trial is warranted for confirm our finding.

Melflufen plus dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) exposed/refractory to prior alkylators: A pooled analysis of the O-12-M1 and HORIZON studies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8048-8048
Author(s):  
Paula Rodríguez-Otero ◽  
Maria-Victoria Mateos ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Blade ◽  
...  
Keyword(s):  
Safety Profile ◽  
Alkylating Agents ◽  
Safety Data ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Study Entry ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Clinical Trial Information

8048 Background: Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate (PDC) that leverages aminopeptidases and rapidly releases alkylating agents inside tumor cells. Melflufen has a mechanism of action distinct from other alkylating agents (Slipicevic et al. AACR 2020. Abs. 1843). In the O-12-M1 (NCT01897714) and HORIZON (OP-106; NCT02963493) studies, melflufen plus dex showed meaningful efficacy and a clinically manageable safety profile in pts with RRMM (Richardson et al. Lancet Haematol. 2020;7:5; Richardson et al. J Clin Oncol. 2020;Dec 9 [Epub]). This pooled analysis examines pts from these studies exposed to prior alkylators. Methods: Both the O-12-M1 and HORIZON studies included pts with RRMM who received ≥ 2 prior lines of therapy (LoTs) and had a primary endpoint of overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) and safety. Data from the 2 studies were pooled and analyzed according to previous exposure and refractoriness to alkylators before study entry. Refractoriness to prior alkylator therapy was defined as disease that failed to achieve a minimal response or progressed while on therapy, or within 60 d of last therapy. Results: Of 202 pts (HORIZON: n = 157, cutoff January 14, 2020; O-12-M1: n = 45, cutoff October 29, 2019), 178 (88%) had been exposed to alkylators in ≥ 1 prior LoT (see Table for subgroups). Pts exposed and refractory to alkylators in ≥ 2 LoTs had the highest number of pts refractory to an alkylator in the last LoT (61%), and 82% were refractory to an alkylator within 12 mo of study entry. Meaningful response rates were seen in all subgroups, except for pts who were exposed and refractory to alkylators in ≥ 2 prior LoTs (see Table). PFS trended toward being shorter with higher exposure and refractoriness to prior alkylators. Results should be interpreted with caution due to limited pt numbers. Grade 3/4 adverse events (AEs) were similar between pts exposed to prior alkylators (O-12-M1: 85%; HORIZON: 89%) and the overall population (O-12-M1: 84%; HORIZON: 89%). The most common AEs were hematologic, but were mostly reversible and clinically manageable. Nonhematologic AEs were infrequent and primarily grade 1/2. Conclusions: Melflufen in combination with dex showed meaningful efficacy and a clinically manageable safety profile in pts with RRMM exposed/refractory to prior alkylators. Clinical trial information: NCT02963493 and NCT01897714. [Table: see text]

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