Eligibility of metastatic pancreatic adenocarcinoma (MPA) patients for first-line palliative intent nab-paclitaxel plus gemcitabine (NG) versus FOLFIRINOX (FIO).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 259-259 ◽  
Author(s):  
Renata D'Alpino Peixoto ◽  
Daniel John Renouf ◽  
Howard John Lim ◽  
Winson Y. Cheung
Keyword(s):  
Performance Status ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Pivotal Phase ◽  
Entire Cohort ◽  
Palliative Intent ◽  
Practice Methods ◽  
Ecog Ps

259 Background: The ACCORD 11 and the MPACT trials recently showed superiority of FIO and NG over gemcitabine alone, respectively. However, both trials had strict inclusion criteria. The aim of this study was to determine the proportion of patients (pts) with MPA who would be potentially eligible for first-line palliative intent chemotherapy with FIO and NG in routine clinical practice. Methods: 473 consecutive pts who presented with MPA and initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the BC Cancer Agency were identified using the provincial pharmacy database. Clinicopathological variables and treatment outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the criteria as described in the respective pivotal phase III trials. Results: In total, median age was 66 years (range 34–89) and 258 (55%) were men. Only 24.7% of the pts would be eligible for FIO as compared to 45.2% for NG. The main reasons for ineligibility for FIO were ECOG performance status (PS) ≥ 2 (56.5%), age > 76 years (19.0%), and bilirubin > 1.5 times the upper limit of the normal range (ULN) (18.6%). The main reasons for ineligibility for NG were bilirubin > ULN (24.5%), ECOG PS ≥ 3 (14.6%), and cardiac dysfunction (13.8%). Median overall survival (OS) for the entire cohort treated with gemcitabine was 5.8 months (95% CI 5.4-6.2). On univariate analyses, eligible pts for FIO had longer median OS than ineligible pts (8.6 vs 4.7 months, p<0.001). Eligible pts for NG also had longer median OS than those deemed ineligible (6.7 vs 4.9 months, p=0.008). After accounting for ECOG PS in the multivariate model, eligibility for either FIO or NG no longered predicted for better OS. Conclusions: In ourpopulation-based analysis, almost twice as many pts would be eligible for NG when compared to FIO, mostly due to ECOG PS. The longer OS observed in the FIO-eligible population likely reflects the exclusion of ECOG PS 2 pts.

Impact of age on safety and efficacy of first-line FOLFOXIRI/bevacizumab in mCRC: A pooled analysis of TRIBE and TRIBE2 studies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3536-3536
Author(s):  
Federica Marmorino ◽  
Daniele Rossini ◽  
Giuseppe Aprile ◽  
Mariaelena Casagrande ◽  
Sara Lonardi ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Performance Status ◽  
Primary Prophylaxis ◽  
Pooled Analysis ◽  
Relative Increase ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Safety And Efficacy ◽  
Ecog Ps

3536 Background: FOLFOXIRI/bevacizumab is a valuable upfront option in mCRC based on results of phase III TRIBE and TRIBE2 studies: 1187 pts aged 18–70 years with ECOG performance status (PS) ≤ 2 or between 71–75 years with an ECOG PS of 0 were randomized to receive first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI in TRIBE and mFOLFOX6 in TRIBE2)/bevacizumab. Here, we aimed at assessing the effect of the intensification of the upfront chemotherapy (triplet versus doublet) in terms of safety and efficacy in pts aged < 70 versus 70-75. Methods: Subgroup analyses for ORR, PFS, G3/4 overall adverse events (AEs), chemo-related and bevacizumab-related AEs were performed according to baseline age. Results: 182 (15%) out of 1187 pts were 70-75 years old (97 in the FOLFOXIRI/bevacizumab and 85 in the doublets/bevacizumab arms). The benefit provided by the intensification of the upfront chemotherapy was independent of the age subgroup in terms of both ORR (p for interaction = 0.684) and PFS (p for interaction = 0.634). The risk of overall and chemo-related G3/4 AEs was increased with the triplet independently of age (p for interaction = 0.736 and 0.790), while no difference in bevacizumab-related AEs was observed in both subgroups (p for interaction = 0.566). In the overall population, as compared to younger pts, those aged 70-75 were more susceptible to overall G3/4 AEs (70% vs 57%, p = 0.001). In the FOLFOXIRI/bevacizumab arm a higher incidence of G3/4 diarrhea (27% vs 17%, p = 0.016) and febrile neutropenia (16% vs 6% p = 0.001) and a lower incidence of all grade nausea (51% vs 65%, p = 0.009) and vomiting (26% vs 44% p = 0.001) were reported among elderly pts. Conclusions: The activity and efficacy of FOLFOXIRI/bevacizumab are confirmed among selected pts between 70 and 75 years old, with a relative increase in the risk of chemo-related AEs similar to that of younger pts. However, elderly pts are more susceptible to experience AEs independently of the treatment arm. Considering the increased incidence of febrile neutropenia and diarrhea with FOLFOXIRI/bevacizumab, the use of G-CSF as primary prophylaxis or an initial dose reduction of irinotecan and 5-fluorouracil might be considered in this population.

Bevacizumab improves outcomes of patients with metastatic colorectal cancer (mCRC) treated with IFL with or without bevacizumab (BV) independent of baseline risk

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3539-3539
Author(s):  
F. Kabbinavar ◽  
A. Zurlo ◽  
C. Irl ◽  
H. Hurwitz
Keyword(s):  
Performance Status ◽  
Risk Groups ◽  
Phase Iii ◽  
Baseline Risk ◽  
First Line ◽  
Tumour Site ◽  
Ecog Performance Status ◽  
Cell Counts ◽  
Wbc Count ◽  
Ecog Ps

3539 Background: It has been reported that patients with mCRC obtain benefit from BV independent of baseline risk factor status. Analysis of 3,825 patients treated with 5-FU/LV in 19 randomised trials conducted by Koehne et al. [Ann Oncol 2002;13:308–17] showed that four baseline prognostic variables can be used to categorise patients into three prognostic groups with different overall survival (OS). We have retrospectively applied this model to data from a phase III trial of first-line IFL with placebo or BV (AVF2107g). Methods: Data on ECOG performance status (PS), tumour site, alkaline phosphatase (AP) levels and white blood cell counts (WBC) were prospectively collected for the 813 patients randomised in AVF2107g. These data were retrospectively used to categorise patients in the IFL/placebo (n=411) and IFL/BV (n=401; data not available for 1 patient) arms into three risk groups: Low - ECOG PS 0/1, one tumour site; intermediate - ECOG PS 0/1, >1 tumour site, AP level <300U/L, or ECOG PS >1, low WBC count, one tumour site; high - ECOG PS 0/1, >1 tumour site, AP level >300U/L, or ECOG PS >1, high WBC count, >1 tumour site. Median OS and PFS in these groups were calculated. Results: OS (Table) and PFS were significantly longer in the IFL/BV groups compared to the IFL/placebo groups, as well as in the lower compared to the higher risk groups in both arms. Conclusions: The analysis supports previous analyses showing that adding BV to IFL improves OS independent of baseline patient risk. Furthermore, high-risk patients, who are less likely to benefit from IFL, benefit from IFL/BV. The model developed by Koehne et al may be applicable to regimens other than 5-FU/LV and validates the efficacy of BV first line in mCRC. [Table: see text] [Table: see text]

Update results from ALTER-C-001: Efficacy and safety of anlotinib plus XELOX regimen as first-line treatment followed by maintenance monotherapy of anlotinib for patients with mCRC-A single-arm, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15550-e15550
Author(s):  
Jin Yan ◽  
Yunwei Han ◽  
Li Zhang ◽  
Yongdong Jin ◽  
Hao Sun
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Ecog Performance Status ◽  
Multicenter Phase ◽  
First Line Treatment

e15550 Background: The combination of anti-VEGF or anti-EGFR targeted drugs with chemotherapy is the standard first-line therapy for metastatic colorectal cancer (mCRC), and the followed maintenance treatment is an optional approach to balance the efficacy and toxicity. However, studies regarding the maintenance strategies based on antiangiogenic TKIs are limited currently. Anlotinib, a novel oral multi-target TKI which can inhibit both tumor angiogenesis and tumor cell proliferation simultaneously, substantially prolonged the PFS with manageable toxicity for refractory mCRC in the phase III ALTER0703 clinical trial. Here we report an update on the effectiveness and safety of anlotinib plus XELOX as first-line treatment followed by anlotinib monotherapy for mCRC. Methods: In this open label, single-arm, multicenter phase II clinical trial, 53 mCRC patients without prior systemic treated, aged 18-75 and an ECOG performance status of 0 or 1 were planned to recruit. Eligible patients received capecitabine (1000 mg/m2, po, d1-14, q3w) and oxaliplatin (130 mg/m2, iv, d1, q3w) plus anlotinib (10mg, po, d1̃14, q3w) treatment for 6 cycles. After 6 cycles of inducing therapy, patients would receive anlotinib (12mg, po, d1̃14, q3w) as maintenance therapy until disease progression or intolerable adverse events (AEs). The primary endpoint was PFS; Secondary endpoints included ORR, DCR, DOR and safety. Results: By the data analysis cutoff date of January 22, 2021, a total of 18 patients were enrolled, of which 12 patients were available for efficacy assessment. In best overall response assessment, there were 50.0% PR (6/12), 33.3% SD (4/12) and 16.7% PD (2/12). The ORR was 50.0% (95% CI, 21.1-78.9%) and DCR was 83.3% (95% CI, 51.5-97.9%). The longest duration of treatment was 8.8 months and the response was still ongoing. The median PFS was not reached. The most common treatment related adverse events (TRAEs) of any grade (≥20%) were leukopenia, hypertension, neutropenia, diarrhea, fatigue, hypertriglyceridemia. Grade 3/4 TRAEs included hypertension (22.2%), hypertriglyceridemia (11.1%), lipase elevated (11.1%) and neutropenia (5.6%). No grade 5 AEs occurred. Conclusions: The update results suggested that anlotinib combined with XELOX as first line regimen followed by anlotinib monotherapy showed promising anti-tumor activity and manageable safety for patients with mCRC. And the conclusions needed to be confirmed in trials continued subsequently. Clinical trial information: ChiCTR1900028417.

Randomized phase II study of biweekly gemcitabine (gem)-paclitaxel (pac), gem-carboplatin (carb) and gem-cisplatin (cis) as first-line treatments in metastatic breast cancer (MBC) after anthracycline failure

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1099-1099 ◽  
Author(s):  
B. Xu ◽  
Z. Jiang ◽  
S. Kim ◽  
S. Yu ◽  
J. Feng ◽  
...  
Keyword(s):  
Performance Status ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Dominant Type ◽  
Tumor Involvement ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
Tumor Types

1099 Background: Biweekly gem-pac and gem-cis regimens have shown promising activity and safety in different tumor types. In MBC biweekly gem-pac is active and well tolerated. The aim of this multi-country study is to evaluate the efficacy and safety of gem in combination with pac, carb or cis on a biweekly schedule in patients (pts) with MBC. Methods: Major eligibility criteria included: tissue diagnosis of stage IV breast carcinoma; prior anthracycline therapy; ECOG performance status (PS) of 0 or 1; and written informed consent. Pts were randomized to receive gem 2500 mg/m2 in combination with pac 150 mg/m2 (Arm A), carb AUC 2.5 (Arm B) or cis 50 mg/m2 (Arm C) on day 1 of 2-week cycles. The primary endpoint was response rate, with safety a secondary endpoint. Results: This interim analysis was planned to occur when patient enrollment had reached 50% (75/150 pts), at which point there were 26 pts in Arm A, 25 in Arm B and 24 in Arm C, with 12 pts still on treatment. The baseline characteristics were similar in the three arms, including mean age (Arm A 50.2 yr, Arm B 46.1, Arm C 47.3); ECOG PS (PS 0: 50.0%, 64.0%, 54.2%); mean number of sites of tumor involvement (2.9, 2.6, 2.7); dominant type of metastasis (visceral: 73.1%, 80.0%, 79.2%); and disease-free interval (<24 mo: 53.8%, 60.0%, 41.7%). The mean number of cycles was 6.4, 6.0 and 5.8. There was a partial response in 5/26 efficacy qualified pts (19.2%), 5/25 pts (20.0%) and 2/23 pts (8.7%) in Arms A, B and C, respectively, stable disease in 10 pts (38.5%), 9 pts (36.0%) and 9 pts (39.1%), and progressive disease in 5 pts (19.2%), 6 pts (24.0%) and 6 pts (26.1%). There were no treatment-related deaths. Conclusions: The three regimens appear to show activity and have manageable toxicity when given on a biweekly schedule. [Table: see text] No significant financial relationships to disclose.

Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4000-4000 ◽  
Author(s):  
E. Van Cutsem ◽  
M. Nowacki ◽  
I. Lang ◽  
S. Cascinu ◽  
I. Shchepotin ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Ecog Performance Status ◽  
Skin Reactions ◽  
Group A ◽  
Group B ◽  
First Line Treatment

4000 Background: Cetuximab in combination with irinotecan-based regimens has proven activity in previously-treated patients (pts) with mCRC. The present trial investigated the effectiveness of cetuximab in combination with standard FOLFIRI compared with FOLFIRI alone in the first-line treatment of pts with epidermal growth factor receptor (EGFR)-expressing mCRC. Methods: Pts were randomized 1:1 to receive either cetuximab (400 mg/m2 initial dose then 250 mg/m2/week [w]) plus FOLFIRI q 2 w (irinotecan 180 mg/m2, FA 400 mg/m2, 5-FU bolus 400 mg/m2, 5-FU infusion 2,400 mg/m2 over 46 hours) (Group A) or FOLFIRI alone (Group B). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate (RR), disease control rate and safety. 633 events were required to statistically differentiate PFS between groups with 80% power. Results: Between August 2004 and October 2005, 1,217 pts were randomized, 608 to Group A and 609 to Group B (60% male, median age 61 [19–84], ECOG performance status: 0=54%; 1=43.5%; 2=3.5%). Median PFS was significantly longer for Group A compared to Group B (8,9 months [8 - 9,5] for Group A vs. 8 months [7.6 - 9] for Group B, p=0.036). Response Rate was also significantly increased by cetuximab (46.9% vs. 38.7%, p=0.005). Treatment was generally well tolerated with neutropenia (26.7% Group A, 23.3% Group B), diarrhea (15.2% and 10.5% respectively) and skin reactions (18.7% and 0.2% respectively) being the most common grade 3/4 adverse events. Conclusions: Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone. [Table: see text]

Defining “cisplatin ineligible” patients with metastatic bladder cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 238-238 ◽  
Author(s):  
M. D. Galsky ◽  
N. M. Hahn ◽  
J. E. Rosenberg ◽  
G. Sonpavde ◽  
W. K. Oh ◽  
...  
Keyword(s):  
Performance Status ◽  
First Line ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Consensus Definition ◽  
Medical Oncologists ◽  
Metastatic Urothelial Carcinoma ◽  
Survey Results ◽  
Definition Of ◽  
First Line Treatment

238 Background: Cisplatin-based chemotherapy is standard first-line treatment for patients (pts) with metastatic urothelial carcinoma (UC). However, a large proportion of pts with UC are considered “unfit” for cisplatin, leading to clinical trials designed specifically for cisplatin-ineligible pts, with substantial variability in eligibility criteria. A clear and consistent definition of pts “unfit” for cisplatin-based therapy will aid in the development of standard eligibility criteria. Methods: We assembled a panel of GU medical oncologists and followed a three-fold approach. First, we surveyed 120 international GU medical oncologists. Subsequently, we reviewed the literature regarding ‘cisplatin ineligibility‘ in solid tumors. Finally, the panel reconciled the survey results and available literature and generated a consensus definition. Results: Responses were received from 65/120 (54%) of those surveyed. The survey results are shown in the Table . Reconciling the survey results with the available literature, the panel recommended the following be used to consistently define pts with metastatic UC “unfit” for cisplatin-based chemotherapy for clinical trial purposes: (1) ECOG performance status of 2 and/or (2) creatinine-clearance < 60 ml/min and/or (3) CTCAE Gr ≥ 2 hearing loss and/or (4) CTCAE Gr ≥ 2 neuropathy. Conclusions: Substantial variability exists in investigators' definitions of pts with metastatic UC “unfit” for cisplatin. A consensus definition is proposed for standardization of eligibility criteria. [Table: see text] No significant financial relationships to disclose.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev as first-line treatment of metastatic colorectal cancer (mCRC): Updated survival results of the phase III TRIBE trial by the GONO group.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Chiara Cremolini ◽  
Fotios Loupakis ◽  
Gianluca Masi ◽  
Vittorina Zagonel ◽  
Francesca Bergamo ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Primary Tumor ◽  
Response Rate ◽  
Performance Status ◽  
Survival Rates ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Term Survival

657 Background: The phase III TRIBE trial met its primary endpoint, by demonstrating that first-line FOLFOXIRI plus bev significantly prolongs PFS, as compared to FOLFIRI plus bev. Also RECIST response rate, early response rate and deepness of response were significantly increased. At the first statistical analysis, with a median follow-up of 32.2 months, OS results were considered preliminary. Methods: Between July 2008 and May 2011, 508 patients were randomized to either FOLFIRI plus bev (arm A, n=256) or FOLFOXIRI plus bev (arm B, n=252). Both treatments were administered for a maximum of 12 cycles followed by 5FU/bev until progression. Results: At a median follow-up of 48.1 months, 374 deaths were recorded (Arm A=200 vs. Arm B=174). Median OS for Arm B vs. Arm A was 29.8 vs. 25.8 months (HR=0.80, 95% CI, 0.65-0.98, p=0.030). Long-term survival rates are reported in Table 1. Treatment effect was consistent across all analyzed subgroups. Among clinical variables, ECOG performance status of 1 or 2, right-sided primary tumor, synchronous metastases, disease not confined to the liver, unresected primary tumor, high Kohne score negatively affected prognosis at univariate analyses. At an exploratory model accounting for these variables, adjusted HR for treatment effect on OS was 0.77 (95% CI, 0.61-0.96, p=0.020). Conclusions: FOLFOXIRI plus bev improves survival of mCRC patients, as compared to FOLFIRI plus bev. The estimated 5-years OS rate of patients treated with FOLFOXIRI plus bev was equal to 24.9%, with an absolute benefit of 12.5% compared to controls. FOLFOXIRI plus bev represents a valuable option for the upfront treatment of mCRC. Clinical trial information: NCT00719797. [Table: see text]

Phase III LEAP-010 study: first-line pembrolizumab with or without lenvatinib in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6589-TPS6589 ◽  
Author(s):  
Lillian L. Siu ◽  
Barbara Burtness ◽  
Ezra E.W. Cohen ◽  
Kevin Joseph Harrington ◽  
Lisa F. Licitra ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Imaging ◽  
Performance Status ◽  
Objective Response ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor ◽  
End Points

TPS6589 Background: The PD-1 inhibitor pembrolizumab is currently approved as first-line monotherapy for patients with R/M HNSCC whose tumors express PD-L1 combined positive score (CPS) ≥1. In a phase 1b/2 trial (NCT02501096) of pembrolizumab plus lenvatinib (multikinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRa, RET, and KIT) in solid tumors, the combination demonstrated promising antitumor activity and a manageable safety profile in patients with HNSCC. LEAP-010 (NCT04199104) is a randomized, double-blind, placebo-controlled, phase 3 study that will evaluate the efficacy and safety of first-line pembrolizumab with or without lenvatinib in patients with PD-L1–positive R/M HNSCC. Methods: Key eligibility criteria include histologically confirmed R/M HNSCC incurable by local therapies, PD-L1–positive tumor (CPS ≥1) as determined by central laboratory, measurable disease as assessed by blinded independent central review (BICR) per RECIST v1.1, and ECOG performance status (PS) 0 or 1. Patients will be randomly assigned 1:1 to pembrolizumab plus lenvatinib or pembrolizumab plus placebo. Randomization will be stratified by PD-L1 status defined by tumor proportion score ( < 50% vs ≥50%), human papillomavirus status for oropharynx cancer (positive vs negative), and ECOG PS (0 or 1). Patients will receive intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles (~2 years) and oral lenvatinib 20 mg or placebo once daily; patients may continue to receive lenvatinib or placebo after pembrolizumab treatment is complete. Treatment will continue until BICR-verified disease progression or unacceptable toxicity. Pembrolizumab retreatment (second course) for 17 additional cycles will be allowed for eligible patients who stop pembrolizumab and subsequently experience BICR-verified disease progression. These patients could have stopped treatment with stable disease, partial response, or complete response or after 35 cycles of pembrolizumab for reasons other than disease progression or toxicity. Tumor imaging assessment will be performed at week 6, then every 6 weeks until 1 year, and thereafter every 9 weeks. Primary end points are objective response rate and progression-free survival, assessed by BICR per RECIST v1.1, and overall survival. Secondary end points are duration of response and safety and tolerability. Recruitment is ongoing; planned enrollment is ~500 patients. Clinical trial information: NCT04199104 .

scholarly journals Multiple Myeloma (MM) in the Very Old: Disease Characteristics, Treatment Patterns and Outcomes in the Real World

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Smith Giri ◽  
Susan Bal ◽  
Kelly N. Godby ◽  
Grant R Williams ◽  
Luciano J. Costa ◽  
...  
Keyword(s):  
Older Adults ◽  
High Risk ◽  
Research Funding ◽  
Performance Status ◽  
Surrogate Marker ◽  
Progression Free Survival ◽  
First Line ◽  
Ecog Performance Status ◽  
Systems Research ◽  
Ecog Ps

Introduction: Older adults with MM continue to remain under-represented in clinical trials, leading to paucity of information regarding the clinical characteristics and treatment outcomes, particularly among those 80y or older at the time of diagnosis. The International Myeloma Working Group (IMWG) classifies any patient &gt;80y as frail, irrespective of their fitness status. The value of geriatric assessment and frailty evaluation in this subgroup remain unclear. Methods: We used the Flatiron Health electronic record-derived de-identified database to source patients with incident MM diagnosed between January 1, 2011 and February 1, 2020. We compared clinical and demographic characteristics of patients ≥80y at the time of diagnosis with patients who were &lt;80y of age. We abstracted baseline labs and cytogenetic data documented within 90 days from the start of first-line therapy. For those ≥80y, we captured the receipt of first line anti-myeloma therapy and examined early mortality (death within 6 months of diagnosis), derived progression-free survival (dPFS) and overall survival (OS) using Kaplan-Meier methods and Cox multivariate regression, with date of diagnosis as the index date. Finally, we compared dPFS and OS among potentially fit ≥80yo MM vs those between 75-79y, using ECOG performance status (PS) of zero as a surrogate marker of fitness status. Results: Of 8298 MM patients in this cohort, 1144 (13.5%) patients were ≥80y at diagnosis (median 81y, range 80-85y). Compared with the younger cohort, those ≥80y were more likely to be white, and have anemia, renal insufficiency, higher β2-microglobulin and higher stage at diagnosis. However, there was a lower prevalence of documented high-risk cytogenetic abnormalities, particularly high risk translocations (t4;14 and t14;16) even after adjusting for race/ethnicity (Mantel Haenszel OR=0.67; p 0.001). Common first line therapies included proteasome inhibitor (PI) + Immunomodulatory agent (Imid) based triplet (23%), Imid doublet (21%) and PI doublet (27%) (Table). Patients ≥80y received a median of 1 (IQR 1-2) lines of therapy, as opposed to those &lt;80 (median 2, IQR 1-3). Overall, the outcome was significantly inferior among the ≥80y patients be those &lt;80y (median dPFS 16 vs. 39 months, p&lt;0.01; median OS: 26 vs 37 months, p&lt;0.01; and 6-month mortality rate: 20.1% vs 6.2%, p&lt;0.01). However, patients ≥80y and ECOG PS of 0 had similar 3y-dPFS (36.8 vs 33.1%; p=0.66) and 3y-OS (61.8 vs 65.2%; p=0.50) when compared to those between 75-79y with similar PS (ECOG PS of 0) (Figure). Conclusion: Patients 80y or above with newly diagnosed MM have distinct clinical and treatment characteristics as compared to their younger counterparts. Similar survival outcomes between older adults with good performance status vs their younger fit counterparts suggest the need for conducting a comprehensive frailty evaluation and individualized decision-making even in this cohort. Disclosures Giri: Carevive Systems: Honoraria; Pack Health: Research Funding; Carevive Systems: Research Funding. Costa:Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; Sanofi: Consultancy, Honoraria.

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