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.

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.

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]

A pooled safety and efficacy analysis examining the effect of performance status (PS) on outcomes in nine first-line treatment (rx) trials (cts) of 6,286 patients (pts) with metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4011-4011 ◽  
Author(s):  
R. M. Goldberg ◽  
C. H. Köhne ◽  
M. T. Seymour ◽  
A. de Gramont ◽  
R. Porschen ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Performance Status ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Phase Iii ◽  
First Line ◽  
Safety And Efficacy ◽  
Efficacy Analysis ◽  
All Cause Mortality ◽  
Grade 3

4011 Background: While pt PS is a known prognostic factor in MCRC, most phase III CTs enroll < 10% PS2 pts. This pooled analysis compares safety and efficacy in PS 0–1 versus (v) PS 2 MCRC pts on first-line CTs testing both single agents and combination rx. Methods: This retrospective analysis included 6,286 MCRC pts (509 PS 2) from 9 CTs (control arms: 5 5FU/LV, 2 FOLFOX, 1 FUFOX, 1IFL). Five CTs specifically compared mono to combination rx (3,814 pts; 335 PS 2). The primary endpoint was progression-free survival (PFS). Other endpoints included grade 3+ adverse events, 60-day all cause mortality, overall survival (OS), and response rate (RR). Efficacy endpoints were explored in both the full set of 9 CTs & the subset of 5 CTs that compared mono to combination rx. Results: Severe (grade 3+) nausea (7.0% v 13.0%; P < .0001), vomiting (6.4% v 10.5%; P = .0002), and stomatitis (2.0% v 4.2%; P = .0332) were significantly higher in PS 2 pts. PS 2 was not associated with incidence of severe diarrhea or neutropenia. 60-day all cause mortality was significantly higher in PS 2 pts (2.8% v 12.0% in PS 0–1 v PS 2 respectively, P <.0001). PS 2 was a prognostic factor for PFS (HR=1.52, P < .0001, median 7.6 v 4.9 months (mos) in PS 0–1 v 2), OS (HR=2.18, P < .0001, median 17.3 v 8.5 mos in PS 0–1 v 2), & RR (OR=0.60, P < .0001, 43.5% v 32.0% in PS 0–1 v 2). The relative benefit of experimental (exp) v control rx did not differ in PS 0–1 v PS 2 pts for RR, PFS, or OS (see table ). This was true both when assessing all 9 CTs and the subset of 5 mono v combination rx CTs. Conclusions: In CTs, pts with PS 2 derive similar advantages with regard to efficacy from superior Rx as do pts with PS 0–1, but with higher risk of some gastrointestinal toxicities. Twelve percent of PS 2 pts die within 60 days of rx start. Median OS is < 9 months. While current Rx does provide benefit, new approaches are required to approach 1 year median survival for PS 2 pts. [Table: see text] No significant financial relationships to disclose.

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 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]

To analyze efficacy and safety of pegfilgrastim versus filgrastim in patients with breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20587-e20587 ◽  
Author(s):  
C. T. Satheesh ◽  
S. Tejinder ◽  
J. Ankit ◽  
K. V. Sajeevan ◽  
K. C. Lakshmaiah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Febrile Neutropenia ◽  
Performance Status ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Ecog Performance Status ◽  
Safety And Efficacy ◽  
The Mean ◽  
Support Methods ◽  
To Receive

e20587 Background: We evaluated the safety and efficacy of a single fixed 6 mg dose of pegfilgrastim (a pegylated version of filgrastim) per cycle of chemotherapy, compared with daily administration of filgrastim, in the provision of neutrophil support. Methods: Patients with carcinoma of breast, less than 65 yrs with ECOG performance status 0 or 1 treated at our institution were randomized to receive either a single 6 mg subcutaneous (s.c.) injection of pegfilgrastim or daily 5 mg/kg s.c. injections of filgrastim, after adjuvant or neoadjuvant chemotherapy with doxorubicin, cyclophosphamide and docetaxel (60 mg/m, 600 mg/m2 and 75 mg/m2, respectively)q3 wk. Duration of grade 4 neutropenia (DSN), incidence of febrile neutropenia (FN), grade 4 neutropenia (SN), IV anti-infective use (IV), hospitalization and adverse events like bony pain (BP), anemia & thrombocytopenias were assessed as safety endpoints. Results: 71 patients were analyzed from Aug 2007 to Dec 2008. The median age in pegfilgrastim group is 58 years and filgrastim is 57 years respectively. Results are shown ( Table ). The mean duration of grade 4 neutropenia (DSN) in cycle 1 was 2.0 and 1.7 days for the pegfilgrastim and filgrastim groups, respectively. Results for all efficacy end points in cycles 2–6 were consistent with the results from cycle 1. A trend towards a lower incidence of febrile neutropenia was noted across all cycles with pegfilgrastim compared with filgrastim (10.7% versus 18.6%, respectively). Conclusions: A single fixed dose of pegfilgrastim administered once per cycle of chemotherapy was comparable to multiple daily injections of filgrastim. [Table: see text] No significant financial relationships to disclose.

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.

Age, gender, and performance status effects on efficacy of 3 versus 6 months of adjuvant oxaliplatin and fluoropyrimidine chemotherapy for stage III colon cancer: Phase III ACHIEVE trial as part of the IDEA collaboration.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 731-731
Author(s):  
Takeshi Kato ◽  
Takayuki Yoshino ◽  
Takeharu Yamanaka ◽  
Masahito Kotaka ◽  
Dai Manaka ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Treatment Duration ◽  
Performance Status ◽  
Disease Free Survival ◽  
Female Gender ◽  
Phase Iii ◽  
Stage Iii ◽  
Ecog Performance Status ◽  
Subgroup Analyses ◽  
Ecog Ps

731 Background: ACHIEVE, a part of the IDEA collaboration, was a multicenter trial randomizing patients with stage III resected colon cancer to either 3 versus 6 months of mFOLFOX6/CAPOX. The primary endpoint was disease-free survival (DFS). We previously reported that the hazard ratios (HRs) of 3 versus 6 months duration in this study according to risk stage (low-risk [T1-3 and N1] or high-risk [T4 or N2]) and regimen (mFOLFOX6 or CAPOX) as well as in overall population were consistent with those observed in the whole IDEA. Methods: ACHIEVE enrolled 1313 patients in Japan between August 2012 and June 2014, out of whom 1291 pts were analyzed for efficacy analysis. As of June 2017, 291 DFS events were observed with a median follow-up time of 39 months. The HR of DFS in the overall population was 0.95 (0.76—1.20) with a 3-year DFS of 80% in 3 months arm and 78% in 6 months arm. In the current study, we investigated subgroup analyses for DFS including age, gender, and ECOG performance status (PS). Results: Outcomes of subgroup analyses are summarized in the Table. With regard to HRs and upper bound on the confidence intervals, the trend of 3 months arm being slightly inferior to 6 months arm in patients with an age of ≥70, female gender, and an ECOG PS of 1; however, there was no evidence of significant interaction across treatment duration and the subgroups. Conclusions: The treatment duration effect did not depend on age, gender, and ECOG PS. Further results according to risk stage and regimen will be presented. Clinical trial information: UMIN 000008543. [Table: see text]

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