Two parallel randomized phase II studies of selumetinib (S) and erlotinib (E) in advanced non-small cell lung cancer selected by KRAS mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8026-8026 ◽  
Author(s):  
Corey Allan Carter ◽  
Arun Rajan ◽  
Eva Szabo ◽  
Sean Khozin ◽  
Anish Thomas ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Single Agent ◽  
Objective Response ◽  
Standard Of Care ◽  
Primary Resistance ◽  
Kras Mutations ◽  
Phase Ii Studies ◽  
Platinum Based Chemotherapy ◽  
Kras Status ◽  
Never Smokers

8026 Background: KRAS mutations are present in 20% of NSCLC and are associated with primary resistance to erlotinib (E). KRAS mutations result in constitutive activation of the Ras/Raf/MEK/ERK pathway. Selumetinib (S) (AZD6244, ARRY-142886) is a selective and uncompetitive inhibitor of MEK kinase. Preclinical studies demonstrated increased activity in NSCLC cell lines using S+E regardless of KRAS status. Methods: Advanced NSCLC patients with progressive disease after platinum based chemotherapy +/- one other treatment were stratified by KRAS status, which was centrally assessed using macrodissection and pyrosequencing for all mutations involving codons 12, 13, and 61. Patients were randomized to receive either the standard of care E or a combination of S+E in KRAS wild type (wt) and S alone or S+E in patients with KRAS mutations. Single agent E and S were administered orally at 150 mg daily and 75 mg twice daily respectively. Combination dosing were S 150 mg every morning and E 100 mg every evening. The primary endpoint for the KRAS wt group was PFS and for the KRAS mutant group objective response rate. Results: From March 2010 to January 2013, 79 patients screened; 78 enrolled: KRAS mutant, 39; KRAS wt, 40; M/F (39:39); median age: 64 years (33-84); median WHO PS 1(0-2); 66 former and 13 never smokers; 67 adenocarcinoma, 9 squamous cell. Three patients died of complications prior to first evaluation (1 coronary disease, 1 pulmonary fibrosis, and 1 disease progression) of which none were related to S. Dose reductions occurred in 5% E, 40% S, and 56% E+S. Most grade 3/4 AEs occurred in combination therapy; diarrhea (23%), fatigue (23%) lymphopenia (13%), myositis (10%), dyspnea (10%), rash (7%). Discontinuation due to AEs was 8% all occurring in S+E cohorts. Conclusions: This study failed to show improvement of combination therapy over single agent in KRAS wt and mutant patients. Toxicity was increased in the combination arms. Interestingly, the KRAS mutant cohort had longer PFS than KRAS wt patients, although not statistically significant (p=0.11). Clinical trial information: NCT01229150. [Table: see text]

Efficacy of anti-PD(L)1 therapy for patients (Pts) with advanced urothelial carcinoma (aUC) with primary resistance to platinum-based chemotherapy (PC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16515-e16515
Author(s):  
Tyler F. Stewart ◽  
Nikhil V. Kotha ◽  
Hannah Elizabeth Dzimitrowicz ◽  
Dimitrios Makrakis ◽  
Ali Raza Khaki ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Cox Regression ◽  
Single Agent ◽  
Objective Response ◽  
Locoregional Therapy ◽  
High Risk Population ◽  
Primary Resistance ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Line Of Therapy

e16515 Background: PC remains standard first-line (1L) therapy for aUC. Approximately 15% of pts exhibit primary resistance (P-R) to PC and ∼25% progress by 4 months. PD(L)1 inhibitors yield objective response rates (ORR) of ∼20% in pts with progression after PC; however, it is unclear if this benefit extends to pts with P-R to PC. We examined the efficacy of anti-PD(L)1 in pts with aUC who experienced P-R to 1L PC. Methods: We conducted a multi-institutional retrospective study of pts with aUC who experienced P-R to PC and were subsequently treated with single-agent anti-PD(L)1 therapy. Eligibility included pts with unresectable or metastatic disease diagnosed after January 1, 2017. P-R to PC was defined as radiographic progression by RECISTv1.1 within 12 weeks from initiation of PC. Pts who developed metastatic disease while receiving (neo)adjuvant PC were eligible. Clinicopathologic variables were collected. ORR to anti-PD(L)1 was the primary endpoint. Secondary endpoints included time to treatment failure (TTF, defined as time from start of anti-PD(L)1 therapy to next line of therapy, hospice or death) and overall survival (OS) were estimated using Kaplan-Meier method. Multivariate (MV) analysis using Cox regression evaluating factors associated with OS was performed. Results: Overall, 42 pts were included: 74% male, median age 65 (28-90); 79% ever smokers; 21% mixed histology; 31% received definitive locoregional therapy. Metastatic sites at diagnosis of aUC included: lymph node only (19%), liver (29%), bone (38%) and lung (33%). At diagnosis of aUC, ECOG PS was 0 in 26%, 1 in 52% and unknown in 21%. 1L PC included cisplatin (76%) and carboplatin (24%) based regimens. Anti-PD(L)1 was received either 2L (98%) or 3L (2%). Overall, ORR to anti-PD(L)1 was 17%: CR (2%), PR (14%), SD (14%), PD (57%) and unknown (12%). Of the 24 pts with PD as best response to anti-PD(L)1, only 9 (38%) received subsequent therapy. Overall, median TTF was 4.2 mo (95% CI 2.8-6.7 mo) and median OS was 7.4 mo (95% CI 4.2-11.1 mo). ORR in patients with a PDL1 combined positive score ≥ 10% (n=6) was 0%: 1 SD and 5 PD. MV analysis for OS from start of anti-PD(L)1 is shown (Table). Conclusions: P-R to PC portends a poor prognosis in pts with aUC. While a subset of patients may respond to anti-PD(L)1 therapy, the majority of pts do not derive benefit. Alternative agents, e.g. antibody drug conjugates and FGFR inhibitors, and combination-therapy should be investigated for this high risk population.[Table: see text]

Final results of a randomized, double-blind, phase II study of gemcitabine plus vandetanib or plus placebo in the treatment of advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) elderly patients (ZELIG study NCT00753714).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7550-7550 ◽  
Author(s):  
Cesare Gridelli ◽  
Silvia Novello ◽  
Nicoletta Zilembo ◽  
Paolo Foa ◽  
Adolfo G. Favaretto ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Standard Of Care ◽  
Primary Objective ◽  
Stage Iiib ◽  
Double Blind ◽  
Platinum Based Chemotherapy

7550 Background: Vandetanib (V) is a once-daily oral inhibitor of VEGFR, EGFR and RET signaling. Single-agent gemcitabine (G) is a standard of care option for unselected patients (pts) unfit for doublet platinum based chemotherapy. This study assessed the progression-free survival (PFS) benefit of G+V compared to G plus placebo (P) in pts with advanced NSCLC aged ≥ 70 years. Methods: Eligible pts (stage IIIB/IV NSCLC; WHO PS 0-2; all histologies; chemonaïve, aged ≥70) were randomized 1:1 to receive G 1200 mg/m2 i.v. day 1 and 8 of each 21-day cycle, up to 6 cycles plus V 100 mg/day or plus P until progression/toxicity. The primary objective was PFS (80% power to detect a hazard ratio [HR] ≤ 0.667). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Between Oct 2008-May 2010, 124 pts (median age 75 yrs (70-84); 72.6% male; 57.2% WHO PS 0-1; 74.2% past/never-smoker; 58.1% adenocarcinoma; 89.5% stage IV) were randomized to G+V (n = 61) or G+P (n = 63). Baseline characteristics were similar in both arms. At data cut-off (Apr11), 87.9% pts progressed and 73.4% pts had died. PFS was significantly prolonged for G+V (HR=0.729; 95% CI 0.484-1.096; p=0.0417), median PFS G+V=6.0 months, G+P=5.5 months. No differences were seen in ORR (14.8% and 12.7%; p = 0.74), DCR (72.1% and 66.7%; p =0.51), OS (HR=1.024 [95% CI 0.667-1.571] p=0.8960), proportion of pts alive at 1-year G+V=31.1% and G+P=30.2% (p=0.90). Adverse events (AEs) observed for V 100 mg were generally consistent with previous NSCLC studies of V 100 mg. Common AEs (any grade) occurring with a greater frequency in the G+V arm included skin toxicity (34.4% vs 15.9%) and hypertension (9.8% vs 3.2%). Diarrhea and neutropenia were similar in both arms (14.8% and 14.3%; 19.7% and 19.0%). Conclusions: Despite a marginally statistically significant improvement in PFS the study did not met the primary and secondary end points. The combination G+V was well tolerated in this clinical setting.

scholarly journals Under-Treatment of Older Patients with Newly Diagnosed Epithelial Ovarian Cancer Remains an Issue

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 952
Author(s):  
Lucy Dumas ◽  
Rebecca Bowen ◽  
John Butler ◽  
Susana Banerjee
Keyword(s):  
Ovarian Cancer ◽  
Older Women ◽  
Older Patients ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Standard Of Care ◽  
First Line ◽  
Care Treatment ◽  
Platinum Based Chemotherapy ◽  
Standard Of Care Treatment

Older women with ovarian cancer have disproportionately poorer survival outcomes than their younger counterparts and receive less treatment. In order to understand where the gaps lie in the treatment of older patients, studies incorporating more detailed assessment of baseline characteristics and treatment delivery beyond the scope of most cancer registries are required. We aimed to assess the proportion of women over the age of 65 who are offered and receive standard of care for first-line ovarian cancer at two UK NHS Cancer Centres over a 5-year period (December 2009 to August 2015). Standard of care treatment was defined as a combination of cytoreductive surgery and if indicated platinum-based chemotherapy (combination or single-agent). Sixty-five percent of patients aged 65 and above received standard of care treatment. Increasing age was associated with lower rates of receiving standard of care (35% > 80 years old versus 78% of 65–69-year-olds, p = 0.000). Older women were less likely to complete the planned chemotherapy course (p = 0.034). The oldest women continue to receive lower rates of standard care compared to younger women. Once adjusted for Federation of Gynaecology and Obstetrics (FIGO) stage, Eastern Cooperative Oncology Group (ECOG) performance status and first-line treatment received, age was no longer an independent risk factor for poorer overall survival. Optimisation of vulnerable patients utilising a comprehensive geriatric assessment and directed interventions to facilitate the delivery of standard of care treatment could help narrow the survival discrepancy between the oldest patients and their younger counterparts.

scholarly journals Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma

2021 ◽  
Vol 9 (6) ◽  
pp. e002057
Author(s):  
Yousef Zakharia ◽  
Robert R McWilliams ◽  
Olivier Rixe ◽  
Joseph Drabick ◽  
Montaser F Shaheen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Advanced Melanoma ◽  
Free Survival ◽  
Programmed Death ◽  
Evaluable Population

BackgroundThe indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.MethodsPatients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.ResultsBetween July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator’s choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).ConclusionIn this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.

Salvage immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) combination therapy for metastatic renal cell carcinoma (mRCC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16567-e16567
Author(s):  
Anish B. Parikh ◽  
Sarah P. Psutka ◽  
Yuanquan Yang ◽  
Katharine Collier ◽  
Abdul Miah ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Free Survival ◽  
Kaplan Meier ◽  
Grade 3 ◽  
Combination Regimens

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

Assessment of sacituzumab govitecan (SG) versus treatment of physician’s choice (TPC) cohort by agent in the phase 3 ASCENT study of patients (pts) with metastatic triple-negative breast cancer (mTNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Joyce O'Shaughnessy ◽  
Kevin Punie ◽  
Mafalda Oliveira ◽  
Filipa Lynce ◽  
Sara M. Tolaney ◽  
...  
Keyword(s):  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Antibody Drug Conjugate ◽  
Phase 3 ◽  
Chemotherapy Agent ◽  
Recist 1.1 ◽  
Duration Of Response ◽  
Grade 3

1077 Background: In pts with pretreated mTNBC, standard-of-care chemotherapy is associated with low objective response rates (ORRs) and short median progression-free survival (PFS). SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG received accelerated FDA approval for treatment of pts with mTNBC who have received ≥2 prior therapies for metastatic disease. The confirmatory phase 3 ASCENT study (NCT02574455) in pts with relapsed/refractory mTNBC demonstrated a significant survival benefit of SG over TPC (median PFS: 5.6 vs 1.7 mo, HR 0.41, P< 0.0001; median overall survival [OS]: 12.1 vs 6.7 mo, HR 0.48, P< 0.0001) with a tolerable safety profile. Here we summarize efficacy results for SG vs each TPC agent in ASCENT to examine how each TPC agent performed individually. Methods: Pts had mTNBC refractory to or progressing after ≥2 prior standard chemotherapy regimens. Pts were randomized 1:1 to receive SG (10 mg/kg intravenously on days 1 and 8, every 21 days) or single-agent TPC (eribulin, vinorelbine, capecitabine, or gemcitabine). Primary endpoint was PFS per RECIST 1.1 by independent review in brain metastases-negative (BMNeg) pts. Secondary endpoints were ORR per RECIST 1.1, duration of response, OS, and safety. Outcomes for each of the agents in the TPC arm were analyzed and compared with SG. Results: Of 529 pts enrolled, 468 were BMNeg. Among pts in the TPC cohort (n = 233), eribulin was the most commonly chosen chemotherapy (n = 126), followed by vinorelbine (n = 47), capecitabine (n = 31), and gemcitabine (n = 29). Treatment with eribulin, vinorelbine, capecitabine, and gemcitabine resulted in shorter median PFS vs SG (2.1, 1.6, 1.6, and 2.7 vs 5.6 mo, respectively); similar results were observed for median OS (6.9, 5.9, 5.2, and 8.4 vs 12.1 mo), ORR (5%, 4%, 6%, and 3% vs 35%), and clinical benefit rate (CBR; 8%, 6%, 10%, and 14% vs 45%). Key grade ≥3 treatment-related adverse events (TRAEs) with TPC overall vs SG included neutropenia (33% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), and anemia (5% vs 8%). Key grade ≥3 TRAEs with eribulin vs SG included neutropenia (30% vs 51%), leukopenia (5% vs 10%), fatigue (5% vs 3%), anemia (2% vs 8%), and peripheral neuropathy (2% vs none), respectively. The safety profiles of vinorelbine, capecitabine, and gemcitabine combined were consistent with that of TPC overall and with eribulin. One treatment-related death was reported for the TPC arm (eribulin) and none with SG. Conclusions: The efficacy benefit observed with SG vs TPC in pts with mTNBC was retained when evaluating each TPC chemotherapy agent individually. These results confirm that SG should be considered as a new standard of care in pts with pretreated mTNBC. Clinical trial information: NCT02574455 .

Response to selpercatinib versus prior systemic therapy in patients (pts) with RET fusion+ non-small-cell lung cancer (NSCLC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9032-9032
Author(s):  
Alexander E. Drilon ◽  
Oliver Gautschi ◽  
Benjamin Besse ◽  
Vivek Subbiah ◽  
Daniel Shao-Weng Tan ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Kinase Inhibitor ◽  
Phase 1 ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Survival Duration ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Systemic Therapies

9032 Background: Selpercatinib, a first-in-class highly selective, potent, CNS-active RET kinase inhibitor, is approved in multiple countries for treatment of RET fusion+ lung or thyroid cancers. Selpercatinib demonstrated durable antitumor activity in previously treated pts with RET fusion+ NSCLC in an ongoing Phase 1/2 trial, LIBRETTO-001 (Besse et al., ASCO 2021). Methods: Pts with RET fusion+ NSCLC enrolled in the global, multicenter, LIBRETTO-001 trial (NCT03157128; 16 countries, 89 sites). Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival, duration of response, and safety. This post-hoc intrapatient analysis was based on a 30 March 2020 data cutoff date. Historical physician-reported best overall response (BOR) from last systemic therapy received prior to enrollment was compared with selpercatinib BOR by independent review committee per RECIST v1.1, with each patient serving as his/her own control. Results: In efficacy-evaluable pts (N = 218) who previously received platinum-based chemotherapy (chemo), median pt age was 61 years, the majority with ECOG of 0/1 (37%/61%), with a median of 2 (range: 1-15) prior systemic therapies. Overall, 57% of patients responded to selpercatinib while 16% responded to the immediate prior therapy. ORR improvements with selpercatinib were observed regardless of prior therapy: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%), or chemotherapy (58% vs 15%). A total of 108 patients (49%) did not respond to immediate prior therapy but responded to selpercatinib. Fewer patients had progressive disease as their BOR with selpercatinib (2%) compared to the immediate prior therapy (28%). The median duration of therapy for selpercatinib was notably extended compared with that of the immediate prior therapy (11.8 vs. 3.4 months, respectively). Conclusions: In pts with RET fusion+ NSCLC treated on LIBRETTO-001, systemic therapies administered prior to enrollment achieved less meaningful clinical benefit than selpercatinib. Selpercatinib demonstrated consistent efficacy regardless of the type of prior therapy. Clinical trial information: NCT03157128.

Use of anti-EGFR agents among elderly patients with metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 657-657 ◽  
Author(s):  
Ashley James D'Silva ◽  
Efrat Dotan ◽  
Dwight D. Kloth ◽  
Andrew Beck ◽  
Steven J. Cohen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Combination Therapy ◽  
Elderly Patients ◽  
Treatment Initiation ◽  
Single Agent ◽  
Stage Iv ◽  
Cancer Center ◽  
Hematologic Toxicity ◽  
Kras Status ◽  
Grade 3

657 Background: Limited data are available regarding the tolerance of older mCRC patients to anti-EGFR therapy. To evaluate the treatment patterns and tolerability of cetuximab/panitumumab in this patient population, we conducted a retrospective review of elderly patients treated with these agents at Fox Chase Cancer Center between 2004-2010. Methods: Patients ≥ age 65 with mCRC treated with cetuximab/panitumumab were included in the analysis. Patient demographics, disease characteristics, treatment drugs and duration, KRAS status and overall survival were recorded. Toxicity evaluation included review of common hematologic and non-hematologic toxicities seen with these agents. Results: 118 patients were included; 100 received cetuximab and 18 received panitumumab therapy. The majority of patients were male (59.3%) with colon cancer (82.2%) and stage IV disease at presentation (50.8%). The median age at treatment initiation was 73 yrs (range: 65-90). Median overall survival was 510 days, and the median time on treatment 73 days. Most patients were treated prior to the incorporation of routine KRAS testing thus, KRAS status was available for 35 patients (29.7%) with 14.2% KRAS mutant tumors. 66% of cetuximab and 45% of panitumumab treatments were given in combination with another agent. The overall incidence of any grade 3/4 non-hematologic toxicity was 36% (34% for single agent; 37.8% for combination therapy). Common grade 3/4 non-heme toxicities were: hypomagnesemia-16.9%, diarrhea-10.2%, and rash-9.3%. Diarrhea and hypomagnesemia were more common among patients receiving combination therapy. The overall incidence of any grade 3/4 hematologic toxicity was 15.2% (6.8% for single agent ; 20.3% for combination therapy). Anemia was the most common heme toxicity in both single and combination therapy. Advanced age at treatment initiation was associated with higher incidence of single agent therapy (p=0.0005, ANOVA statistics). Conclusions: Our data demonstrate that elderly patients with mCRC tolerate anti-EGFR therapy, with toxicity rates similar to those reported in large clinical trials with younger patient populations. Older mCRC patients can safely receive anti-EGFR treatment as part of their therapy.

Biochemotherapy versus chemotherapy for metastatic malignant melanoma: A meta-analysis of the randomised trials

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8544-8544 ◽  
Author(s):  
N. J. Ives ◽  
R. L. Stowe ◽  
P. Lorigan ◽  
K. Wheatley
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Interleukin 2 ◽  
Standard Of Care ◽  
Response Rates ◽  
Complete Response ◽  
Metastatic Malignant Melanoma ◽  
Published Data ◽  
The Individual

8544 Background: Metastatic melanoma is associated with a poor survival rate. High response rates have been reported for both chemotherapy and biochemotherapy. To assess whether adding interferon-a (IFN) ± interleukin-2 (IL-2) to chemotherapy is advantageous, a published data meta-analysis of trials of biochemotherapy versus chemotherapy has been performed. Methods: Standard published data meta-analysis methods were used to assess response rates (partial, complete and objective (i.e. partial+complete)) and overall survival (OS), with odds ratios (OR) and 95% confidence intervals (CI) calculated. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to the type of immunotherapy given in the biochemotherapy arm - IFN or IFN+IL-2. Results: Data were available from 18 trials (11 trials of chemotherapy ± IFN and 7 of trials chemotherapy ± IFN+IL-2). Nearly 2500 patients were included in the analysis, with 555 responses and 2,039 deaths observed. There was a clear benefit for biochemotherapy for partial response (OR=0.67, CI=0.54–0.83, p=0.0002), complete response (0.50, 0.35–0.73, p=0.0003) and objective response (0.60, 0.49–0.73, p<0.00001). For objective response, these benefits were significant for both the IFN (0.60, 0.46–0.79, p=0.0002) and IFN+IL2 (0.60, 0.45–0.78, p=0.00002) subgroups. In contrast, there was no benefit on OS (0.99, 0.91–1.08, p=0.9), and there was also evidence of heterogeneity of treatment effect between the individual trials (p=0.006). Conclusions: This meta-analysis shows that biochemotherapy clearly improves response rates, but this does not appear to translate into a survival benefit. Single agent chemotherapy is considered the standard of care for the majority of patients receiving treatment for advanced melanoma outside a clinical trial, and the result of this meta-analysis shows no reason to change this. No significant financial relationships to disclose.

Updated analysis of a phase II study (20060314) of panitumumab (pmab) with FOLFIRI as first-line treatment of patients (pts) with metastatic colorectal cancer (mCRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4085-4085
Author(s):  
R. Greil ◽  
H. Letocha ◽  
E. Gamelin ◽  
J. Thaler ◽  
R. Hofheinz ◽  
...  
Keyword(s):  
Adverse Event ◽  
Combination Therapy ◽  
Phase Ii ◽  
Interim Analysis ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
First Line ◽  
Kras Status ◽  
Ecog Ps

4085 Background: The fully human anti-epidermal growth factor receptor monoclonal antibody pmab, has proven monotherapy activity in chemotherapy refractory mCRC pts with wild-type KRAS-expressing tumors. This first-line, single-arm phase II study is prospectively evaluating whether KRAS status predicts response to treatment when pmab is combined with FOLFIRI. Methods: In this ongoing study, pts with histologically confirmed mCRC (no prior systemic treatment) and ECOG PS 0–2 were enrolled at 36 sites across Europe. Pmab (6mg/kg) and FOLFIRI are administered every 2 weeks. The primary endpoint is objective response rate; secondary endpoints include disease control rate, duration of response, time to response, progression-free survival, time to progression and safety. Results: Data cut-off for the initial interim analysis was 27 June 08 and pending approval of protocol amendment 2, the cut off date for 16 week response rate is 15 Oct 08. Of the 154 pts enrolled, 68% are male; median age is 64 yrs (range, 21–84) and the majority (95%) of pts had ECOG PS 0–1. All pts have received at least one cycle of study treatment; 18% of pts have received ≤2 cycles of full combination therapy and the median number of cycles received is 6. At time of data cut-off, 112 patients (73%) were still receiving at least one element of combination therapy and 29% had stopped treatment with pmab. The most common reason for discontinuing treatment was disease progression (10%). Median follow-up time was 14.3 weeks for all enrolled pts. A total of 97% of patients had experienced at least one adverse event (any grade) and 55% of patients had experienced a grade 3/4 adverse event. There were four reported grade 5 events (hematemesis, rectal hemorrhage, vena cava thrombosis, general physical health deterioration). At time of interim analysis, tissue samples for KRAS analysis are available for approximately 80% of patients. Conclusions: Combining pmab with FOLFIRI in the first-line setting appears to be a well-tolerated regimen. Response rate at 16 weeks in the overall population and by KRAS status and updated safety will be presented. [Table: see text]

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