Potential of 2018 ASH CLL Data to Alter Standard of Care for Initial CLL Treatment

Introduction In the past 5 years, four drugs have received approval for the treatment of Chronic lymphocytic leukemia (CLL), with most of the data supporting their approvals presented at an ASH meeting. How treating hematologists and oncologists (H/O) incorporate these agents into their practice has implications for all stakeholders. We conducted market research with H/O to understand how CLL data presented at ASH 2018 might alter their treatment preferences. Methods A live meeting in February 2019 convened H/O. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting and responded to questions regarding their perceptions on the data and its potential impact on current practice. The presentations used included the following: 1) Alliance A041202: a phase III, randomized study in older patients with untreated CLL comparing ibrutinib ± rituximab with bendamustine + rituximab (BR) (Woyach JA, et al. Blood. 2018;132[Suppl 1]:6); and 2) E1912: a phase III, randomized study in younger patients with untreated CLL comparing ibrutinib + rituximab with fludarabine + cyclophosphamide + rituximab (FCR) (Shanafelt TD, et al. Blood. 2018;132[Suppl 1]:LBA-4). Participants submitted their demographic responses via a web-based survey and data impression responses via an audience response system at the live meeting. Results 59 H/O participated in this live market research on February 22-23, 2019 and identified their primary specialty as 61% hematologist/oncologist and 34% medical oncologist. The participants were mostly community-based physicians, 50% in private community and 45% in community practices owned by a hospital or academic center. Over one-third have been in practice >20 years and see an average of 20+ patients per day. In the prior 3 months, 31%, 27%, and 18% of the participants initiated first-line treatment on 1, 2, or 3 CLL patients, respectively. The most commonly preferred first-line treatments for CLL patients ≥65 years without del(17p) were: BR (38%), ibrutinib (34%), anti-CD20 monotherapy (17%), and FCR (7%). Based on the results of the Alliance A041202 trial, 88% are likely to use single-agent ibrutinib as their preferred first-line therapy for older CLL patients, 45% very likely and 43% moderately likely. The most commonly preferred first-line treatments for CLL patients <65 years without del(17p) were: FCR (37%), BR (30%), ibrutinib (18%), and ibrutinib + anti-CD20 monotherapy (13%). Based on the results of the E1912 trial, the participants are likely to adopt ibrutinib + CD20 monoclonal antibody (51%), single-agent ibrutinib (20%), FCR (16%), or BR (13%) as their preferred first-line therapy for younger CLL patients. Conclusion Studies of newer mechanism of action drugs like Bruton's tyrosine kinase (BTK) inhibitors are perceived as compelling by treating oncologists and appear likely to replace more traditional chemotherapy-based regimens. The clinical, financial, and patient-centric outcomes of such rapid changes to standard of practice warrant further research. Disclosures Feinberg: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Gajra:Cardinal Health: Employment.

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Health related quality of life (HRQOL) evaluated with the EORTC C30 questionnaire in first line therapy of elderly patients with chronic lymphocytic leukemia (CLL): Results of a phase III trial of the German CLL Study Group (GCLLSG)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7572 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7572-7572 ◽

Cited By ~ 1

Author(s):

B. F. Eichhorst ◽

R. Busch ◽

M. Hallek

Keyword(s):

Social Functioning ◽

Age Groups ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

Response To Treatment ◽

First Line ◽

Elderly Age ◽

First Line Therapy ◽

Line Therapy ◽

Significant Difference

7572 Background: The GCLLSG evaluated the efficacy of fludarabine (F) versus (vs.) chlorambucil (Clb) in first line therapy of older patients with advanced CLL. HRQOL was evluated by using the EORTC C30 questionnaire. Methods: Pts were randomized to receive 6 courses of F (25 mg/m²/day (d) IV for 5d; 92 pts) or 12 months (mo) of Clb (0.4–0.8 mg/kg/d PO, every 15d; 99 pts). All pts were previously untreated, aged between 65 and 79 years and in advanced stage Binet C or symptomatic Binet B or A. Primary endpoints were overall survival (OS) and progression free survival (PFS), secondary endpoint was HRQOL. The EORTC C30 questionnaire (version 2.0) was sent to all patients at baseline and after 6, 12 and 24 mo. Scores (0–100) for 15 different measures (1 global HRQOL, 5 functional, 3 symptom and 6 single item scales) were evaluated at each time point. Results: F induced significantly higher response rates and prolonged the PFS, while no significant difference in OS was observed. At baseline 130 of 191 pts (68%) completed the questionnaires followed by more than 80% at mo 6 to 24. Compliance rates were similar in both treatment arms. Between pts completing questionnaires or not no statistically significant differences in perfomance status, age, stage or response to treatment were observed. HRQOL differences in comparison to baseline values were significantly improved after F treatment in global HRQOL, role and social functioning after 12 months as shown by the table. Responders had a significantly better global HRQOL and social functioning as well. Except for an impaired physical functioning no differences in HRQOL were observed between different age groups (65–69, 70–74, 75–79). Conclusion: Elderly F treated patients with CLL showed improvement inglobal HRQOL. Elderly age groups had a similar HRQOL as younger age groups. [Table: see text] [Table: see text]

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Cladribine Alone or in Combination with Cyclophosphamide or Cyclophosphamide and Mitoxantrone as First Line Treatment in Chronic Lymphocytic Leukemia: An Early Report of Prospective Randomized Study.

Blood ◽

10.1182/blood.v104.11.337.337 ◽

2004 ◽

Vol 104 (11) ◽

pp. 337-337 ◽

Cited By ~ 1

Author(s):

Tadeusz Robak ◽

Jerzy Z. Blonski ◽

Joanna Gora-Tybor ◽

Marek Kasznicki ◽

Jadwiga Dwilewicz-Trojaczek ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Residual Disease ◽

Early Report ◽

Randomized Study ◽

Lymphocytic Leukemia ◽

P Value ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Minimal Residual

Abstract The aim of the study was to determine the efficacy and toxicity of cladribine alone (2-CdA) and in combination with cyclophosphamide - CY (CC) or CY and mitoxantrone - MIT (CMC) in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia in a randomized, multicenter study. 2-CdA was given at a dose of 0.12 mg/kg/d in 2 h I.V. infusion for 5 consecutive days in monotherapy and for 3 days in combination. In CC and CMC programmes cyclophosphamide was administered at a dose of 650 mg/m2 I.V. on day 1 and additionally mitoxantrone 10 mg/m2 I.V. on day 1 in CMC. Courses were repeated at 28 day intervals or longer if myelosuppression and/or infection developed, for a maximum of 6 courses. The response criteria were those recommended by NCI sponsored Working Group. Minimal residual disease (MRD) were evaluated by flow cytometry if CR was achieved. In conclusion, the results of our study indicate that 2-CdA combined with CY or CY+MIT as first line therapy give higher CR rate than 2-CdA alone. However, CMC is more toxic than 2-CdA or CC. We recommend CC combination for further studies. Treatment 2-CdA CC CMC p value Entered pts 167 169 163 Evaluated pts 143 152 139 CR 37 (25.9%) 43 (28.3%) 55 (39.6%) 0.03 OR 106 (74.1%) 125 (82.2%) 110 (79.1%) 0.2 MRD 15 (46.9%) 22 (82.2%) 25 (56.8%) 0.7 Median OR duration (years) 1.67 1.81 1.43 0.1 Relapse 48 (45.3%) 45 (29.6%) 43 (30.9%) 0.2 AIHA 10 (7.0%) 10 (6.6%) 5 (3.6%) 0.4 Thrombocytopenia grIII/IV 25 (17.5%) 25 (16.4%) 32 (23.0%) 0.3 Neutropenia grIII/IV 27 (18.9%) 43 (28.3%) 52 (37.4%) <0.001 Infections 39 (27.3%) 47 (30.9%) 53 (38.1%) 0.07 Died 39 (27.3%) 30 (19.7%) 37 (26.6%) 0.4

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Perceptions of Community Hematologists/Oncologists on the Potential of Data Presented at ASH 2018 and ASCO 2019 to Alter the Standard of Care for Multiple Myeloma Treatment

Blood ◽

10.1182/blood-2019-129502 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5822-5822

Author(s):

Ajeet Gajra ◽

Richard Sweat ◽

Yolaine Jeune-Smith ◽

Bruce Feinberg

Keyword(s):

Multiple Myeloma ◽

Annual Meeting ◽

Nuclear Export ◽

Market Research ◽

Randomized Study ◽

Single Agent ◽

Standard Of Care ◽

The United States ◽

Phase Iii ◽

Primary Specialty

Introduction There has been a remarkable growth of new therapies for multiple myeloma (MM) in the last 5 years with 5 new agents approved by the FDA. Daratumumab is a human anti-CD38 monoclonal antibody previously approved as a single agent in relapsed/refractory (RR) MM and as combination in relapsed MM. Selinexor represents a novel first-in-class selective inhibitor of nuclear export (SINE) XPO1 antagonist in RRMM. The perception of practicing community hematologists and oncologists (H/O) regarding new information presented at major scientific meetings has implications for all stakeholders including patients, practices, payers, manufacturers and distributors. We conducted market research with H/O to understand how MM data presented at ASH 2018 and ASCO 2019 might alter their treatment preferences. Methods Live meetings in February and June 2019 convened H/O with geographic representations from across the United States. The participants were shown data from selected oral and/or poster presentations from the 2018 ASH Annual Meeting or 2019 ASCO Annual Meeting and responded to questions regarding their perceptions of the data and its potential impact on current practice. The presentations used included the following: 1) MAIA: a phase III, randomized study in patients with transplant-ineligible newly diagnosed MM (NDMM) comparing daratumumab plus lenalidomide and dexamethasone (D-Rd) to lenalidomide and dexamethasone (Rd) alone (Facon T, et al. Blood. 2018;132[Suppl 1]:LBA-2); 2) CASSIOPEIA: a phase III, randomized study in patients with transplant-eligible NDMM comparing daratumumab plus bortezomib, thalidomide and dexamethasone (D-VTd) to bortezomib, thalidomide and dexamethasone (VTd) alone (Moreau P, et al. J Clin Oncol. 2019;37[15_suppl]:8003); and 3) STORM: a pivotal, phase II, single-arm study of selinexor and dexamethasone in patients with penta-refractory MM (Chari A, et al. Blood. 2018;132[Suppl 1]:598). Participants submitted their demographic responses via a web-based survey prior to the meetings and data impression responses via an audience response system at the live meetings. Results Among the 112 H/O who participated in these live market research programs on February 22-23 and June 21-22, 2019, 58% identified their primary specialty as hematology/oncology and 38% medical oncology. Only 27% of the 59 H/O at the February live meeting had attended the ASH 2018 in December 2018 and 43% of the 53 at the June live meeting had attended the ASCO 2019 in June 2019. The participants were mostly community-based physicians, 47% in private community and 48% in community practices owned by a hospital or academic center. 31% have been in practice for over 20 years, 39% for 11-20 years and 29% for 10 or fewer years. The majority of this group sees at least 16 patients per day and reported active MM as one of the three most common hematologic malignancies they manage. At the February 2019 live meeting, 79% of H/O in attendance indicated that, based on the results of the MAIA study, D-Rd is likely to become their standard of care for patients with NDMM who are ineligible for transplant. At the June 2019 live meeting, the majority of H/O in attendance indicated that bortezomib + lenalidomide + dexamethasone (VRd) was the regimen typically used for their transplant-eligible NDMM patients. After reviewing the data from the CASSIOPEIA study of D-VTd, 50% of H/O indicated that the results are practice-changing and will be widely adopted, but thalidomide will be substituted with lenalidomide (D-VRd). 65% of H/O who attended the February 2019 live meeting indicated that, if selinexor is approved by the FDA, they are very likely to consider it for their patients with RRMM. 76% of advisors indicated that selinexor's novel mechanism of action (MOA) is very clinically meaningful in MM. Qualitative data collected also denotes interest in seeing selinexor tested and moved to earlier lines of therapy akin to the development course followed by daratumumab. Conclusions The movement of daratumumab to the first-line setting was well received by the community H/O and their willingness to substitute IMiD drugs in the backbone regimen for transplant-eligible patients was notable. It is noteworthy that the interest in selinexor was high even prior to its FDA approval and especially driven by its novel MOA. Disclosures Gajra: Cardinal Health: Employment. Sweat:Cardinal Health: Employment. Jeune-Smith:Cardinal Health: Employment. Feinberg:Cardinal Health: Employment.

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First-SIGNAL: First-Line Single-Agent Iressa Versus Gemcitabine and Cisplatin Trial in Never-Smokers With Adenocarcinoma of the Lung

Journal of Clinical Oncology ◽

10.1200/jco.2011.36.8456 ◽

2012 ◽

Vol 30 (10) ◽

pp. 1122-1128 ◽

Cited By ~ 456

Author(s):

Ji-Youn Han ◽

Keunchil Park ◽

Sang-We Kim ◽

Dae Ho Lee ◽

Hyae Young Kim ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Group Performance ◽

Single Agent ◽

Eastern Cooperative Oncology Group ◽

Phase Iii ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Never Smokers ◽

Gemcitabine And Cisplatin

Purpose Gefitinib has shown high response rate and improved progression-free survival (PFS) in never-smokers with lung adenocarcinoma (NSLAs). We compared efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this group of patients as first-line therapy. Patients and Methods In this randomized phase III trial, a total of 313 Korean never-smokers with stage IIIB or IV lung adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ function were randomly assigned to receive either gefitinib (250 mg daily) or GP chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1 every 3 weeks, for up to nine courses). The primary objective was to demonstrate better overall survival (OS) for gefitinib compared with GP in chemotherapy-naive NSLAs. Results Three hundred nine patients were analyzed per protocol (gefitinib arm, n = 159; GP arm, n = 150). Gefitinib did not show better OS compared with GP (hazard ratio [HR], 0.932; 95% CI, 0.716 to 1.213; P = .604; median OS, 22.3 v 22.9 months, respectively). The 1-year PFS rates were 16.7% with gefitinib and 2.8% with GP (HR, 1.198; 95% CI, 0.944 to 1.520). Response rates were 55% with gefitinib and 46% with GP (P = .101). Myelosuppression, renal insufficiency, and fatigue were more common in the GP arm, but skin toxicities and liver dysfunction were more common in the gefitinib arm. Two patients (1.3%) in the gefitinib arm developed interstitial lung disease and died. Conclusion Gefitinib failed to demonstrate superior OS compared with GP as first-line therapy for NSLAs.

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First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia

Blood ◽

10.1182/blood-2009-02-206185 ◽

2009 ◽

Vol 114 (16) ◽

pp. 3382-3391 ◽

Cited By ~ 227

Author(s):

Barbara F. Eichhorst ◽

Raymonde Busch ◽

Stephan Stilgenbauer ◽

Martina Stauch ◽

Manuela A. Bergmann ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Elderly Patients ◽

Survival Time ◽

Remission Rate ◽

Progression Free Survival ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

First Line ◽

First Line Therapy ◽

Line Therapy

Abstract Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m2 for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.4 mg/kg body weight [BW] with an increase to 0.8 mg/kg, every 15 days, for 12 months). Fludarabine resulted in a significantly higher overall and complete remission rate (72% vs 51%, P = .003; 7% vs 0%, P = .011). Time to treatment failure was significantly shorter in the chlorambucil arm (11 vs 18 months; P = .004), but no difference in progression-free survival time was observed (19 months with fludarabine, 18 months with chlorambucil; P = .7). Moreover, fludarabine did not increase the overall survival time (46 months in the fludarabine vs 64 months in the chlorambucil arm; P = .15). Taken together, the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil. This trial is registered with www.isrctn.org under identifier ISRCTN 36294212.

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KEYNOTE-177: Phase III randomized study of pembrolizumab versus chemotherapy for microsatellite instability-high advanced colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.6 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 6-6

Author(s):

Kai-Keen Shiu ◽

Thierry Andre ◽

Tae Won Kim ◽

Benny Vittrup Jensen ◽

Lars Henrik Jensen ◽

...

Keyword(s):

Colorectal Cancer ◽

Microsatellite Instability ◽

Randomized Study ◽

Phase Iii ◽

First Line ◽

Meaningful Improvement ◽

End Points ◽

First Line Therapy ◽

Line Therapy ◽

Grade 5

6 Background: KEYNOTE-177 (NCT02563002) evaluated the antitumor activity of pembrolizumab (pembro) vs chemotherapy ± bevacizumab or cetuximab (chemo) as first-line therapy for patients with microsatellite-instability high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). We present results of the final PFS analysis and analysis of PFS2. Methods: Patients with locally-determined MSI-H/dMMR mCRC and ECOG PS 0 or 1 were randomized 1:1 to first-line pembro 200 mg Q3W for up to 2 years or investigator’s choice of mFOLFOX6 or FOLFIRI Q2W ± bevacizumab or cetuximab (chosen before randomization). Treatment continued until progression, unacceptable toxicity, patient/investigator decision to withdraw, or completion of 35 cycles (pembro only). Patients receiving chemo could crossover to pembro for up to 35 cycles after confirmed PD. Primary end points were PFS (RECIST v1.1, central review) and OS. Secondary end points included ORR (RECIST v1.1, central review) and safety. Exploratory endpoints included duration of response (DOR), PFS2 (time from randomization to progression on next line of therapy or any cause death), and health-related quality of life (HRQoL). Data cutoff was Feb 19, 2020. Results: At data cutoff a total of 307 patients were randomized (153 to pembro, 154 to chemo). Median (range) study follow-up was 32.4 mo (24.0-48.3). Pembro was superior to chemo for PFS (median 16.5 mo vs 8.2 mo; HR 0.60; 95% CI, 0.45-0.80; P= 0.0002). The 12- and 24-mo PFS rates were 55.3% and 48.3% with pembro vs 37.3% and 18.6% with chemo. Confirmed ORR was 43.8% vs 33.1%; median (range) DOR was not reached (2.3+ to 41.4+) with pembro vs 10.6 mo (2.8 to 37.5+) with chemo. PFS2 was longer with pembro vs chemo (median not reached vs 23.5 mo [HR 0.63; 95% CI, 0.45-0.88]). OS analysis is ongoing. Grade ≥3 treatment related adverse event (TRAE) rates were 22% vs 66% for pembro vs chemo. There were no grade 5 TRAEs in the pembro arm and 1 grade 5 intestinal perforation in the chemo arm. HRQoL scores were improved with pembro vs chemo. Conclusions: Pembro provided a statistically significant improvement in PFS vs chemo as first-line therapy for patients with MSI-H/dMMR mCRC, with fewer TRAEs observed. Furthermore, pembro provided a clinically meaningful improvement in PFS2 for patients with MSI-H/dMMR mCRC. Clinical trial information: NCT02563002.

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A phase III trial-in-progress comparing tislelizumab plus chemotherapy with placebo plus chemotherapy as first-line therapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps2655 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS2655-TPS2655

Author(s):

Rui-hua Xu ◽

Hendrik-Tobias Arkenau ◽

Yung-Jue Bang ◽

Crystal S. Denlinger ◽

Ken Kato ◽

...

Keyword(s):

Gastroesophageal Junction ◽

Single Agent ◽

Locally Advanced ◽

Predictive Biomarkers ◽

Phase Iii ◽

Tolerability Profile ◽

First Line ◽

Double Blind ◽

First Line Therapy ◽

Line Therapy

TPS2655 Background: In patients (pts) with locally advanced or metastatic G/GEJ cancer, fluoropyrimidine- and platinum (plt)-based combination chemotherapy is first-line standard of care. Despite improvement in chemotherapy regimens, outcomes are poor and survival remains low. Tislelizumab, an investigational anti-PD-1 antibody, was engineered to minimize binding of FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Previous reports suggested tislelizumab, as a single agent and in combination with chemotherapy, was generally well tolerated and had antitumor activity in pts with advanced solid tumors, including G/GEJ cancer. Methods: This global, double-blind, randomized, phase 3 study (NCT03777657) is designed to compare plt/fluoropyrimidine + tislelizumab versus plt/fluoropyrimidine + placebo as first-line therapy for pts with locally advanced or metastatic G/GEJ cancer. Approximately 720 pts from 160 centers will be randomized 1:1 to receive tislelizumab (200 mg IV Q3W) or placebo (IV Q3W) in combination with chemotherapy. Oxaliplatin (130 mg/m² IV Q3W) plus capecitabine (1000 mg/m2 orally twice daily for 2 weeks) or cisplatin (80 mg/m² IV Q3W) plus 5-fluorouracil (800 mg/m2/day IV on Days 1–5 Q3W) will be used as backbone chemotherapy on an individual basis. Chemotherapy will be administered for up to 6 cycles; capecitabine maintenance therapy is optional for pts who received capecitabine and oxaliplatin. PD-L1 expression will be assessed using the VENTANA PD-L1 (SP263) assay. Progression-free survival and overall survival are primary endpoints in the intent-to-treat and PD-L1-positive analysis sets of the study. Secondary endpoints include overall response rate, duration of response, quality-of-life outcomes, and the safety/tolerability profile of combination therapy. Exploratory endpoints include disease control rate, time to response, and an analysis of potential predictive biomarkers including, but not limited to, PD-L1 expression. Clinical trial information: NCT03777657.

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Phase III Study of Capecitabine Plus Oxaliplatin Compared With Continuous-Infusion Fluorouracil Plus Oxaliplatin As First-Line Therapy in Metastatic Colorectal Cancer: Final Report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.8467 ◽

2007 ◽

Vol 25 (27) ◽

pp. 4224-4230 ◽

Cited By ~ 185

Author(s):

Eduardo Díaz-Rubio ◽

Jose Tabernero ◽

Auxiliadora Gómez-España ◽

Bartomeu Massutí ◽

Javier Sastre ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Continuous Infusion ◽

Randomized Study ◽

Phase Iii ◽

High Dose ◽

Final Report ◽

First Line ◽

First Line Therapy ◽

Line Therapy

Purpose The aim of this phase III trial was to compare the efficacy and safety of capecitabine plus oxaliplatin (XELOX) versus Spanish-based continuous-infusion high-dose fluorouracil (FU) plus oxaliplatin (FUOX) regimens as first-line therapy for metastatic colorectal cancer (MCRC). Patients and Methods A total of 348 patients were randomly assigned to receive XELOX (oral capecitabine 1,000 mg/m2 bid for 14 days plus oxaliplatin 130 mg/m2 on day 1 every 3 weeks) or FUOX (continuous-infusion FU 2,250 mg/m2 during 48 hours on days 1, 8, 15, 22, 29, and 36 plus oxaliplatin 85 mg/m2 on days 1, 15, and 29 every 6 weeks). Results There were no significant differences in efficacy between XELOX and FUOX arms, which showed, respectively, median time to tumor progression (TTP; 8.9 v 9.5 months; P = .153); median overall survival (18.1 v 20.8 months; P = .145); and confirmed response rate (RR; 37% v 46%; P = .539). The safety profile of the two regimens was similar, although there were lower rates of grade 3/4 diarrhea (14% v 24%) and grade 1/2 stomatitis (28% v 43%), and higher rates of grade 1/2 hyperbilirubinemia (37% v 21%) and grade 1/2 hand-foot syndrome (14% v 5%) with XELOX versus FUOX, respectively. Conclusion This randomized study shows a similar TTP of XELOX compared with FUOX in the first-line treatment of MCRC, although there was a trend for slightly lower RR and survival. XELOX can be considered as an alternative to FUOX.

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