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Annual Meeting Proceedings Part 1 - American Society of Clinical ...

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4027 Poster Discussion Session (Board #19), Mon, 1:15 PM-5:15 PM and<br />

4:45 PM-5:45 PM<br />

Multicenter randomized phase II trial <strong>of</strong> cisplatin, irinotecan plus bevacizumab<br />

(PCA) versus docetaxel, cisplatin, irinotecan plus bevacizumab<br />

(TPCA) in patients (pts) with metastatic esophagogastric cancer (MEGCA).<br />

Presenting Author: Peter C. Enzinger, Dana-Farber Cancer Institute,<br />

Boston, MA<br />

Background: In MEGCA, PCA has a 65% response rate (RR) and 8.3 mos<br />

time to progression (Shah. JCO 2006); TPCA has a 66% RR and 8.9 mos<br />

progression-free survival (PFS) (Enzinger. ESMO 2008 updated). Methods:<br />

Chemo naive pts with MEGCA were stratified: ECOG (0/1 vs. 2) and disease<br />

site (Gastric or GEJ/esophageal) and randomized 1:1 to PCA or TPCA. PCA<br />

-- cisplatin 30mg/m2 and irinotecan 65mg/m2 on d1, 8, and bevacizumab<br />

10 mg/kg d1 docetaxel 30mg/m2, cisplatin 25mg/m2 and irinotecan<br />

50mg/m2 on d1, 8, and bevacizumab 10 mg/kg d1. Cycles were 3 weeks.<br />

Response assessment - q6wks (RECIST 1.1). Primary endpoint was PFS.<br />

Results: 85 patients: median age�61 (40-85); male/female� 70/15;<br />

ECOG: 0/1/2�(34/49/2); gastric/GE junction/esophageal�27/21/37; measurable/evaluable:<br />

78/7; sites <strong>of</strong> metastatic disease (# <strong>of</strong> pts): lymph nodes<br />

(34), liver (31), lung (11), bone (5), abdomen (4), peritoneum (4), other<br />

(11). There were two treatment-related deaths: esophageal hemorrhage,<br />

sudden death (both TPCA). Conclusions: Both regimens were efficacious<br />

and reasonably well tolerated. The addition <strong>of</strong> docetaxel to the attenuated<br />

PCA combination did not significantly improve efficacy.<br />

PCA (N�44) TPCA (N�41) P value<br />

Major response 56.8% (41.0, 71.7) 48.8% (32.9, 64.9) 0.518<br />

PFS median (N�85) 7.7mos (5.8, 10.1) 8.4mos (6.8, 9.8) 0.861<br />

OS 1-year (N�85) 52.6% (36.0, 66.8) 59.1% (42.2, 72.7) 0.866<br />

OS median (N�85)<br />

Grade III-IV toxicity %<br />

12.5mos (9.6, 15.5) 13.3mos (11.5, 15.4) 0.866<br />

Neutropenia 25.0 31.7 0.492<br />

Thrombocytopenia 4.5 4.9 1.000<br />

Diarrhea 22.7 31.7 0.465<br />

Fatigue 15.9 19.5 0.778<br />

Vomiting 9.1 12.2 0.733<br />

Infection 11.4 7.3 0.714<br />

Anorexia 2.3 9.8 0.192<br />

Thromboembolic 4.5 9.8 0.423<br />

HTN 4.5 4.9 1.000<br />

4029 Poster Discussion Session (Board #21), Mon, 1:15 PM-5:15 PM and<br />

4:45 PM-5:45 PM<br />

The pattern and timing <strong>of</strong> disease recurrence in squamous cancer <strong>of</strong> the<br />

anus: Mature results from the NCRI ACT II trial. Presenting Author: David<br />

Sebag-Montefiore, St James Institute <strong>of</strong> Oncology, Leeds, United Kingdom<br />

Background: Concurrent chemoradiation (CRT) is standard treatment for<br />

patients with squamous cell carcinoma <strong>of</strong> the anus. Although the majority<br />

<strong>of</strong> patients achieve long term disease control, locoregional failure is either<br />

detected early (failure to enter complete remission) or at a later date as<br />

locoregional recurrence. We explore the pattern and timing <strong>of</strong> disease<br />

recurrence within a phase III trial (ACT II), which mandated standardised<br />

radiation fields and doses (50.4Gy in 28 daily fractions). Methods: The UK<br />

ACT II trial recruited a total <strong>of</strong> 940 patients (2000 -2008) and compared<br />

cisplatin with mitomycin when combined with 5flurouracil CRT and two<br />

cycles <strong>of</strong> maintenance chemotherapy versus no maintenance using a<br />

factorial 2x2 design. Patient characterstics: T1/2 52%, T3/4 46%; N�<br />

32% N0 62%. The loco-regional response to treatment was assessed by<br />

clinical examination at 11, 18 and 26 weeks after CRT. <strong>Clinical</strong> examination<br />

was performed every two months for year 1; 3-monthly for year 2; then<br />

6-monthly for years 3-5. CT scans <strong>of</strong> chest/abdomen/pelvis were performed<br />

at 6,12 24 months. Sites <strong>of</strong> failure were recorded on a case record form<br />

(primary site [PS], inguinal [ING], pelvic nodes [PEL], metastatic [METS].<br />

Results: After a median follow up <strong>of</strong> 5 years, the crude pelvic failure (PF)<br />

rate is 18% (163/924). Of the 163 PF, 133 pts (82%) were pelvic only and<br />

30 (18%) had PF � metastasis. 93% <strong>of</strong> all pelvic recurrences were<br />

detected during the first three years (54% yr 1, 26% yr 2 and 13% yr 3).<br />

The pattern was similar for PF only and PF � mets (data not shown). Only<br />

46 (4%) <strong>of</strong> patients had [METS] as the first disease related event. 117/133<br />

(88%) patients with PF only are evaluable for analysis <strong>of</strong> the pattern <strong>of</strong><br />

failure., 53% occurred at the primary site (PS) only, 23% were PS � nodal<br />

(5% [ING] 13% [PEL] and 5% [ING�PEL], and 25% nodal only (6%<br />

[ING],14% [PEL] and 5% [ING�PEL]). Conclusions: The ACT II trial results<br />

with mature follow-up demonstrate a low rate <strong>of</strong> pelvic failure. Intensive<br />

follow up to detect potentially salvageable pelvic failure should be<br />

restricted to a maximum <strong>of</strong> three years in future trials as only 7% <strong>of</strong><br />

relapses occur beyond this time point.<br />

Gastrointestinal (Noncolorectal) Cancer<br />

245s<br />

4028 Poster Discussion Session (Board #20), Mon, 1:15 PM-5:15 PM and<br />

4:45 PM-5:45 PM<br />

A randomized phase II study <strong>of</strong> continuous versus intermittent S-1 plus<br />

oxaliplatin in first-line treatment <strong>of</strong> patients with metastatic gastric<br />

carcinoma. Presenting Author: Sook Ryun Park, Center for Gastric Cancer,<br />

National Cancer Center, Goyang, Gyeonggi, South Korea<br />

Background: We conducted a randomized phase II study to compare<br />

continuous vs. intermittent S-1 � oxaliplatin (SOX) after induction <strong>of</strong> 6<br />

cycles <strong>of</strong> SOX in patients (pts) with metastatic gastric cancer (MGC).<br />

Methods: Pts �18 yrs with chemo-naive MGC, normal organ function,<br />

ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an<br />

induction treatment <strong>of</strong> 6 cycles <strong>of</strong> SOX (S-1 40 mg/m2 bid on D1-14 �<br />

oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were<br />

randomized to continue SOX (arm A) until progression/intolerable toxicity<br />

or discontinue until progression when SOX was re-administered (arm B).<br />

The primary endpoint was overall survival (OS), and secondary endpoints<br />

included progression-free survival (PFS), response rate, safety, quality <strong>of</strong><br />

life, and biomarker correlative studies. Results: From July 2007 to Dec<br />

2010, a total <strong>of</strong> 250 pts entered into the study. Median age was 53 yrs<br />

(range, 24-69); PS 0/1/2�13/219/18; M/F�162/88. Three pts did not<br />

receive treatment and 126 (50.4%) discontinued treatment before or at<br />

the completion <strong>of</strong> 6 cycles <strong>of</strong> SOX due to progression (45.6%), pt refusal<br />

(2.8%), or adverse events (2.0%). A total <strong>of</strong> 121 pts were randomized: 59<br />

(48.8%) to arm A and 62 (51.2%) to arm B. <strong>Clinical</strong> characteristics were<br />

well balanced between arms. SOX continuation resulted in a significant<br />

reduction in the risk <strong>of</strong> progression (median PFS, 10.5 months for arm A vs.<br />

7.2 months for arm B; HR�0.57, 95% CI 0.39-0.84, p�0.005). With a<br />

median follow-up <strong>of</strong> 34.0 months (range, 10.5-53.3 months), there was no<br />

significant difference in OS (median OS, 22.6 months for arm A vs. 22.7<br />

months for arm B; HR, 0.79, 95% CI 0.51-1.25, p�0.31). Arm A had<br />

higher rates <strong>of</strong> grade 3/4 fatigue (28.8% vs. 8.1%, p�0.004) and<br />

neuropathy (25.4% vs. 8.1%, p�0.014) but other grade 3/4 hematologic<br />

(neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%;<br />

anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not<br />

significantly different. Conclusions: Continuous chemotherapy with SOX<br />

after induction therapy improved PFS but not OS. Supported by NCC Grant<br />

1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and<br />

san<strong>of</strong>i-aventis Korea Co., Ltd., respectively).<br />

4030 Poster Discussion Session (Board #22), Mon, 1:15 PM-5:15 PM and<br />

4:45 PM-5:45 PM<br />

Phase II trials <strong>of</strong> cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil<br />

(5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIVpositive<br />

(AMC045) patients with squamous cell carcinoma <strong>of</strong> the anal<br />

canal (SCAC): Safety and preliminary efficacy results. Presenting Author:<br />

Madhur Garg, Albert Einstein College <strong>of</strong> Medicine/Montefiore Medical<br />

Center, Bronx, NY<br />

Background: Epidermal growth factor receptor (EGFR) expression and HPV<br />

infection are common in SCAC. We therefore initiated 2 phase II studies to<br />

evaluate the safety and efficacy <strong>of</strong> the EGFR inhibitor CX given concurrently<br />

with CDDP/5-FU/RT in HIV-positive (AMC045) and immunocompetent<br />

(E3205) patients with SCAC. Methods: All patients received CX (400<br />

mg/m2 loading, then 250 mg/m2/wk IV x 6-8 wks) plus CDDP (75 mg/m2<br />

IV q28 days x 2) and 5-FU (1000 mg/m2/day IV infusion days 1-4 q 28<br />

days x 2) concurrently with RT (45-54 Gy) beginning with CX dose 2.<br />

Patients in E3205 also received 2 cycles <strong>of</strong> CDDP/5-FU alone prior to<br />

CX/CDDP/5-FU/RT; this was discontinued on recommendation <strong>of</strong> the NCI<br />

Anorectal Task Force after 28 patients. Both trials were powered to detect a<br />

reduction in 3-year local-regional failure (LRF) rate from 35% to 17.5%<br />

(alpha�0.10, beta�0.10), the primary end point. Other endpoints included<br />

progression free survival (PFS) and overall survival (OS). The results<br />

below include complete toxicity and preliminary efficacy data (including<br />

only the first 28 patients from E3205). Results: Expedited reporting was<br />

required for type I (any grade 5, grade 4 cardiac) or II (grade 4 RT skin,<br />

diarrhea) adverse events, with prespecified rates <strong>of</strong> �5% or �20%,<br />

respectively defined as unacceptable. Early stopping rules were not invoked<br />

for either trial. LRF rates data will be presented after more detailed case<br />

review is completed. Conclusions: CX plus CDDP/5-FU/RT is feasible in<br />

patients with SCAC, including patients with HIV infection. Preliminary<br />

safety and efficacy data appear encouraging, but accrual without neoadjuvant<br />

CDDP/5-FU continues in E3205, and additional followup <strong>of</strong> both<br />

study cohorts is required in order to determine whether pre-specified<br />

efficacy endpoints were met.<br />

AMC045 E3205<br />

No. 45 28<br />

Stage I/II/III 24%/42%/34% 11%/50%/39%<br />

Completed protocol therapy 37 (82%) 22 (79%)<br />

Type I/II adverse events 2 (4%)/0 1 (4%)/1 (4%)<br />

Colostomy rate 7% (1-18%) 14% (4-33%)<br />

2 year PFS rate (95% CI) 80% (61-90%) 92% (81-100%)<br />

2 year OS rate (95% CI) 89% (73-96%) 93% (83-100%)<br />

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