Randomized, Placebo-Controlled, Phase III Study of Oxaliplatin, Fluorouracil, and Leucovorin With or Without PTK787/ZK 222584 in Patients With Previously Treated Metastatic Colorectal Adenocarcinoma

2011 ◽  
Vol 29 (15) ◽  
pp. 2004-2010 ◽  
Author(s):  
Eric Van Cutsem ◽  
Emilio Bajetta ◽  
Juan Valle ◽  
Claus-Henning Köhne ◽  
J. Randolph Hecht ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Performance Status ◽  
Treatment Options ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Treatment Groups ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Post Hoc

Purpose Treatment options for patients with previously treated metastatic colorectal cancer (mCRC) are limited, and treatments with differing mechanisms of action are needed. PTK787/ZK 222584 (PTK/ZK) is a novel oral angiogenesis inhibitor with therapeutic potential for the treatment of solid tumors. Methods Patients (N = 855) were randomly assigned to treatment with PTK/ZK or placebo once daily in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). Stratification factors included WHO performance status (PS; 0 v 1 to 2) and lactate dehydrogenase ([LDH] ≤ 1.5× the upper limit of normal [ULN] v > 1.5 × ULN). Treatment was given until disease progression or unacceptable toxicity. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, tolerability, and pharmacokinetics of PTK/ZK. Results No statistically significant differences were seen between the treatment groups for the overall comparison of OS. With PTK/ZK and placebo, respectively, median OS was 13.1 and 11.9 months (hazard ratio [HR], 1.00; 95% CI, 0.87 to 1.16; P = .957). Median PFS was longer with PTK/ZK than with placebo (5.6 and 4.2 months, respectively; HR, 0.83; 95% CI, 0.71 to 0.96; P = .013). An exploratory, post hoc analysis demonstrated improved PFS in patients with high LDH, regardless of WHO PS (HR, 0.63; 95% CI, 0.48 to 0.83; P < .001). Conclusion PTK/ZK in combination with FOLFOX4 did not improve OS of patients with pretreated mCRC but did improve PFS. The effect of PTK/ZK was more pronounced in patients with high LDH at baseline.

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.

Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first disease progression (PD) in patients with metastatic colorectal cancer (mCRC) previously treated with BEV-based therapy: Outcomes according to KRAS status and first-line CT backbone in the ML18147 study.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 520-520 ◽  
Author(s):  
Stefan Kubicka ◽  
Richard Greil ◽  
Thierry André ◽  
Jaafar Bennouna ◽  
Javier Sastre ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Therapy Outcomes ◽  
First Line ◽  
Mutant Type ◽  
Post Hoc Analysis ◽  
Kras Status ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Post Hoc

520 Background: ML18147 is the first randomized phase III study to show that continuing BEV + standard CT as second-line (2L) treatment significantly improves overall survival (OS) and progression-free survival (PFS) in patients with mCRC who progressed after receiving a standard first-line (1L) BEV-containing regimen. Here we report an exploratory analysis of outcomes based on CT backbone and KRAS status. Methods: Patients with unresectable, histologically confirmed mCRC who progressed ≤3 months after discontinuing 1L BEV were randomised to 2L CT (crossed over from oxaliplatin to irinotecan and vice versa) ± BEV. This post-hoc analysis evaluated OS, PFS, overall response rate (ORR) and disease control rate (DCR) according to 1L CT backbone (irinotecan- or oxaliplatin-based) and KRAS status (Scorpion ARMS test for KRAS codons 12 and 13). Results: In total, 616 patients (75% of the ITT population) were included in this analysis; 316 had wild-type (WT) and 300 had mutant-type (MT) KRAS status; 355 received 1L irinotecan and 261 received 1L oxaliplatin. BEV+CT beyond PD prolonged OS and PFS vs CT alone, regardless of whether oxaliplatin- or irinotecan-based CT was used in the 1L and whether patients had WT or MT KRAS (Table). Adverse events were not increased when continuing BEV+CT beyond PD and were consistent with previous findings. Conclusions: This post hoc analysis suggests that continuing BEV + 2L oxaliplatin or irinotecan-based CT (following crossover) leads to prolonged OS and PFS, regardless of KRAS status or if oxaliplatin or irinotecan-based CT was used in the 1L. Clinical trial information: NCT00700102. [Table: see text]

Ziv-aflibercept: A novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer

2013 ◽  
Vol 70 (21) ◽  
pp. 1887-1896 ◽  
Author(s):  
Clement Chung ◽  
Nisha Pherwani
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Second Line ◽  
Patient Response ◽  
Line Setting

Abstract Purpose The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of ziv-aflibercept in combination therapy for metastatic colorectal cancer (mCRC) are reviewed. Summary Ziv-aflibercept (Zaltrap, Regeneron Pharmaceuticals and sanofi-aventis) is a novel recombinant fusion protein that targets the angiogenesis signaling pathway of tumor cells by blocking vascular endothelial growth factor (VEGF) receptors that play a key role in tumor growth and metastasis; it is a more potent VEGF blocker than bevacizumab. Ziv-aflibercept is approved by the Food and Drug Administration for use in combination with fluorouracil, irinotecan, and leucovorin (the FOLFIRI regimen) for second-line treatment of patients with mCRC who have disease progression during first-line oxaliplatin-based chemotherapy. A Phase III trial demonstrated that relative to FOLFIRI therapy alone, the use of ziv-aflibercept was associated with significantly improved patient response, overall survival, and progression-free survival in patients with good performance status at baseline, including some who had received prior bevacizumab therapy. The most common grade 3 or 4 adverse effects associated with ziv-aflibercept use in clinical studies were neutropenia, hypertension, and diarrhea; the U.S. product labeling warns of potential hemorrhage and other treatment-related risks. Conclusion Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine

2017 ◽  
Vol 35 (30) ◽  
pp. 3433-3439 ◽  
Author(s):  
George D. Demetri ◽  
Patrick Schöffski ◽  
Giovanni Grignani ◽  
Jean-Yves Blay ◽  
Robert G. Maki ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eribulin Mesylate ◽  
Systemic Treatments ◽  
Phase Iii Study

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

Molecular marker assessments for epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC) and histoscore (H-score) in the phase III SELECT trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8052-8052
Author(s):  
Edward S. Kim ◽  
Sreenivas Chittoor ◽  
Craig H. Reynolds ◽  
Lorinda Simms ◽  
Scott Saxman
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Clinical Results ◽  
Phase Iii ◽  
Egfr Expression ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Epidermal Growth ◽  
Select Trial

8052 Background: SELECT was a phase III study that investigated whether the addition of cetuximab (C) to pemetrexed (P) improved outcome in previously treated patients (pts) with recurrent or progressive non-small cell lung cancer (NSCLC). Clinical results have been reported previously and demonstrated that adding C to P did not improve progression-free survival (PFS) or overall survival (OS). H-score has been reported to be a potential predictor of outcome for C therapy. Prespecified biomarker analyses, including EGFR IHC and H-score, are reported here. Methods: EGFRexpression in tumor tissue was not required for eligibility; however, tissue was collected and analyzed for EGFR expression by IHC using standard methods. In addition, H-score evaluation was performed by trained central pathologists and correlated with clinical outcome using a predefined cutoff for “low” and “high” of <200 and ≥200, respectively. Results: A total of 449 (IHC) and 406 (H-score) pt specimens were evaluable. Demographics for pts with tissue available for EGFR analysis were similar to the overall population. For IHC+ pts (n=396), median PFS for C+P was 3.02 months (95% CI, 2.76–3.45) compared with 2.99 months (95% CI, 2.63–4.14) for P (HR, 1.02 [95% CI, 0.83–1.24]; p=.86). For pts with low H-score (N=99 [C+P] and N=111 [P]), median PFS was 2.7 months (95% CI, 1.8–3.2) with C+P and 3.1 months (95% CI, 2.6–4.1) with P (HR, 1.11 [95% CI, 0.84–1.46]; P=.48); median OS was 6.7 months (95% CI, 5.3–8.6) with C+P and 6.6 months (95% CI, 4.7–9.2) with P (HR, 0.96 [95% CI, 0.72–1.27]; P=.76). Among pts with high H-scores (N=101 [C+P] and N= 95 [P]), median PFS was 3.2 months (95% CI, 2.7–4.6) with C+P and 3.7 months (95% CI, 1.7–4.5) with P (HR, 1.02 [95% CI, 0.77–1.37]; P=.86); median OS was 7.7 months (95% CI, 6.5–10.9) with C+P and 8.0 months (95% CI, 7.0–9.1) with P (HR, 1.17 [95% CI, 0.86–1.57]; P=.32). Conclusions: EGFR H-score was not predictive of benefit for the addition of C to P in this population of pts with NSCLC. There was also no treatment effect in the IHC+ group. Clinical trial information: NCT00095199.

CanStem303C trial: A phase III study of napabucasin (BBI-608) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult patients with previously treated metastatic colorectal cancer (mCRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3619-TPS3619 ◽  
Author(s):  
Axel Grothey ◽  
Manish A. Shah ◽  
Takayuki Yoshino ◽  
Eric Van Cutsem ◽  
Julien Taieb ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Study Population ◽  
Previously Treated ◽  
Line Of Therapy

TPS3619 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapeutics, including 5-FU and irinotecan. Encouraging anticancer activity in advanced CRC was observed in a phase Ib/II (Bendell et al, GI ASCO 2017) study of 63 pts with disease control rate (DCR) of 93% (28/30) and overall response rate (ORR) of 33% (10/30) in FOLFIRI-naïve pts who have had an on-study RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia, and Asia. Methods: This study (ClinicalTrials.gov NCT02753127) will assess the efficacy of napabucasin+FOLFIRI vs FOLFIRI in pts with mCRC (n = 1250). Addition of bevacizumab (bev) is permissible per investigator choice. Pts must have failed 1 prior line of therapy with oxaliplatin and a fluoropyrimidine +/- bev for metastatic disease. Pts are randomized 1:1 to receive napabucasin 240 mg PO BID plus FOLFIRI bi-weekly, or FOLFIRI bi-weekly (bev may be added to FOLFIRI by investigator choice) and stratified by geography, time to progression on 1st-line therapy, RAS mutation status, bev as part of study treatment and primary tumor location. Treatment will continue until disease progression, or another discontinuation criterion. Primary endpoint is overall survival (OS) in the general study population (ITT) (HR 0.80 for OS improvement from 12.54 to 15.68 months); secondary endpoints include OS in the biomarker positive (biomarker+) population, progression free survival (PFS) in the ITT population, PFS in biomarker+ population, ORR and DCR in the ITT and in biomarker+ populations, safety and quality of life. Also, blood and tumor archival tissue will be assessed for PK and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02753127.

CanStem111P trial: A phase III study of napabucasin (BBI-608) plus nab-paclitaxel (nab-PTX) with gemcitabine (gem) in adult patients with metastatic pancreatic adenocarcinoma (mPDAC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4148-TPS4148 ◽  
Author(s):  
Tanios S. Bekaii-Saab ◽  
Chung-Pin Li ◽  
Takuji Okusaka ◽  
Bert H. O'Neil ◽  
Michele Reni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Disease Control ◽  
Performance Status ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Study Population

TPS4148 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinical studies suggest that napabucasin sensitizes heterogeneous cancer cells to chemotherapeutic agents, including nab-PTX and gem. Encouraging anticancer activity in mPDAC was observed in a phase Ib (El-Rayes et al, ASCO 2016) study of 37 pts, reporting 93% (28/30) disease control rate (DCR) and 50% (15/30) overall response rate (ORR), with 1 complete and 14 partial responses and prolonged disease control ( > 24 wks) in 57% (17/30) of pts who have had a RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia and Asia. Methods: This study (ClinicalTrials.gov NCT02993731) will assess the efficacy of napabucasin+nab-PTX+gem vs nab-PTX+gem in pts with mPDAC (n = 1132). Pts must have been diagnosed with mPDAC < 6 weeks prior to randomization and not have received treatment for metastatic disease. Pts are randomized in a 1:1 ratio to receive napabucasin 240 mg PO twice daily continuously plus nab-PTX+gem IV weekly for 3 out every 4 weeks, or nab-PTX+gem IV weekly for 3 out every 4 weeks. Pts will be stratified by geography, performance status and presence of liver metastases. Treatment will continue until disease progression, death, intolerability or patient/investigator decision to stop. Primary endpoint is overall survival (OS) in the general study population (HR 0.80 for OS improvement from 8.5 to 10.63 months); secondary endpoints include progression free survival (PFS), OS and PFS in the biomarker positive sub-population, ORR and DCR, safety and quality of life. In addition, blood and tumor archival tissue will be assessed for pharmacokinetic and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02993731.

Subgroup analysis by measurable metastatic lesion (ML) number and selected lesion locations (LL) at baseline (BL) in NAPOLI-1: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 460-460
Author(s):  
Jens T. Siveke ◽  
Richard Hubner ◽  
Teresa Mercade Macarulla ◽  
Andrea Wang-Gillam ◽  
Andrew Peter Dean ◽  
...  
Keyword(s):  
Metastatic Lesion ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Pivotal Phase ◽  
Clear Trend ◽  
Prognostic Effect ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Liposomal Irinotecan ◽  
Post Hoc

460 Background: We report a post hoc, exploratory analysis of pts with BL ML number and LL data who received nal-IRI+5-FU/LV, nal-IRI or 5-FU/LV in NAPOLI-1, a pivotal, phase 3 trial (NCT01494506). nal-IRI+5-FU/LV increased median OS (mOS) vs 5-FU/LV (6.1 vs 4.2 mo [HR=0.67; p=0.012]). Methods: ML (1, 2, 3, >3) and LL were recorded (local investigator) at BL. Pts with >1 LL were counted for each location. Results: 354 of 417 ITT pts had measurable BL ML and 1,080 LL were recorded. There was no clear trend in the percentage of pts with KPS ≥80 in 1- >3 ML (range 87%-95%) or LL (range 89%-94%) subgroups. ML 1 (n=81), 2 (n=65) and 3 (n=24) subgroups were small. nal-IRI+5-FU/LV significantly improved mOS vs. 5-FU/LV in pts with 2/>3 ML (n=184/24); nal-IRI+5-FU/LV had numerically higher mOS vs. 5-FU/LV for all LL (Table). nal-IRI+5-FU/LV had favourable median PFS (mPFS) vs. 5-FU/LV in pts with 1–>3 ML (range 2.0-4.2 vs. 1.4-1.9 mo; HR range 0.35-0.88) and for all LL (range 2.8-4.2 vs. 1.4-2.0 mo; HR range 0.39-0.55). Conclusions: Low pt numbers across groups and repeat counting of pts in LL subgroups preclude firm conclusions on treatment efficacy, pending further analyses. Allowing for these limitations, we detected no clear prognostic effect on outcomes of higher BL ML number or LL in NAPOLI-1 ITT pts. nal-IRI+5-FU/LV improved mOS vs. 5-FU/LV in some ML groups and across LL groups; improvement in mPFS vs. 5-FU/LV in the ITT population was maintained in all subgroups. Clinical trial information: NCT01494506. [Table: see text]

Carfilzomib (K) in relapsed and refractory multiple myeloma (RRMM): Frailty subgroup analysis from phase III ASPIRE and ENDEAVOR.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8028-8028 ◽  
Author(s):  
Thierry Facon ◽  
Ruben Niesvizky ◽  
Katja Weisel ◽  
Sara Bringhen ◽  
P. Joy Ho ◽  
...  
Keyword(s):  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Frailty Status ◽  
Improved Outcomes ◽  
Comorbidity Index ◽  
Post Hoc ◽  
Frailty Score

8028 Background: K-based regimens improved progression-free survival (PFS) and overall survival (OS) in RRMM patients (pts) in ASPIRE (K [27 mg/m2]-lenalidomide-dexamethasone [KRd] vs Rd) and ENDEAVOR (K [56 mg/m2]-dexamethasone [Kd56] vs bortezomib-dexamethasone [Vd]), regardless of age. Frailty scores have been developed based on age, comorbidities, and functional status (Palumbo Blood 2015;125:2068–74; Facon Blood 2015;126:4239). We assessed post hoc pt outcomes by frailty status. Methods: PFS, OS, and safety were assessed by treatment arm and frailty score (based on age, medical history-derived Charlson Comorbidity Index, and ECOG performance status); frailty scores: 0 = fit, 1 = intermediate (int), and ≥2 = frail. Results: Pt frailty status was balanced between treatment arms in ASPIRE and ENDEAVOR. Median PFS and OS were longer with K-based regimens vs controls in ASPIRE and ENDEAVOR across frailty subgroups (Table). Rates of treatment-emergent adverse events are summarized in the Table. Conclusions: Kd56 and KRd consistently improved outcomes vs Vd and Rd, respectively, in all frailty subgroups as defined by the algorithm above. These findings support the favorable benefit-risk profile of KRd and Kd56 regardless of frailty score. Clinical trial information: NCT01080391 and NCT01568866. [Table: see text]

Randomized phase II study of erlotinib alone and in combination with bortezomib in previously treated advanced non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7680-7680 ◽  
Author(s):  
T. J. Lynch ◽  
D. W. Fenton ◽  
V. Hirsh ◽  
D. J. Bodkin ◽  
E. Middleman ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Performance Status ◽  
Treatment Options ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Ecog Performance Status ◽  
Combination Methods ◽  
Previously Treated ◽  
Grade 3

7680 Background: Treatment options for previously treated NSCLC are limited, warranting consideration of novel combinations. This study evaluated the activity and toxicity of erlotinib with bortezomib, a proteasome inhibitor. Dosing was based on the approved indication for erlotinib and on phase I data for the combination. Methods: Patients (pts) with Stage IIIB/IV NSCLC who progressed following one prior line of chemotherapy, with no prior exposure to an EGF-receptor inhibitor and ECOG performance status 0 or 1 were randomly assigned to erlotinib 150 mg po daily alone (arm A) or in combination with bortezomib 1.6 mg/m2 iv on days 1 and 8 (arm B) of a 21-day cycle. Response was evaluated by RECIST and toxicity was graded using NCI CTCAE 3.0. A Simon optimal two-stage design was used to evaluate anti-tumor activity in response-evaluable pts. Results: Fifty pts were treated at 17 sites (January-June 2006); baseline characteristics and treatment intensity were comparable in both arms. Among 24 response-evaluable pts in each arm, there were 3 partial responses (PR) and 1 complete response in arm A and 2 PR in arm B. Median progression-free survival (PFS) was 2.7 and 1.4 months in arms A and B, respectively. The study was halted as required at the planned interim analysis due to insufficient clinical activity in arm B. Activity and toxicity in arm A were consistent with published reports for erlotinib alone. Adverse-event profiles were as expected in both arms, with no significant additivity. In arm B, one pt died of pneumonia. The most common grade 3 treatment-related toxicity was skin rash (12% arm A and 8% arm B), and rash severity correlated with PFS: grades 2/3, 2.8 months PFS (20 pts); grades 0/1, 1.4 months PFS (28 pts), p=0.032. In arm B, one pt each had grade 3 anorexia, hypokalemia, and worsened peripheral sensory neuropathy compared with baseline. There were no grade 4 treatment related toxicities in either arm. Conclusions: The combination of erlotinib and bortezomib in the doses and schedules used in this trial was well tolerated but did not show sufficient activity at this dose and schedule to warrant further development. No significant financial relationships to disclose.

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