SO-30 Efficacy and safety of neoadjuvant short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma: Averectal study

139 Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer is becoming an accepted approach over the last few years with increasing pathologic complete response (pCR) and compliance of patients for chemotherapy in comparison with the current standard of care i.e., fluoropyrimidine based chemoradiation followed by surgery and adjuvant chemotherapy. Sequential use checkpoint inhibitors after radiation therapy (RT) has demonstrated synergistic effect in vivo leading to decrease in size of irradiated and non-irradiated secondary tumors outside the radiation field (abscopal effect). Methods: This is an investigator initiated; open-label, single-arm multicenter phase II study, adopting Simon’s two-stage aiming at evaluating the pCR rate and safety of using short-course radiation therapy (25 Grays in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus Avelumab (anti PDL1), then total mesorectal excision(TME) in patients with locally-advanced, potentially resectable rectal adenocarcinoma. Results: 13 out of 44 patients were accrued from 20, July till 28, Dec 2018 in the first stage of the study (30% from total sample size). They all met the inclusion criteria and received full protocol treatment. 12 out of the 13 completed TME. 1 of the 13 had progression of disease, so surgery was aborted and patient was dropped out the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33.0, 73.0) years. The first interim analysis revealed 3 patients (25%) achieved pCR (tumor regression grade: TRG = 0) out of 12 as compared to the historical control group with pCR of 16%. For the rest of the patients, 3 (25%) had major pathologic response rate (pRR) with TRG = 1 (< 10% viable cells is tumor bed).In total, 6 out of 12 patients (50%) had major pathologic response rate. As for safety, no serious adverse events of grade 3 and 4 were reported. Conclusions: Based on the first interim analysis results, incorporation of Avelumab and short course radiotherapy is tolerable in patients with locally advanced rectal cancer treated with TNT. The study will resume recruitment to reach the target accrual. Clinical trial information: NCT03503630.

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The Impact of Surgical Timing on Pathologic Tumor Response after Short Course and Long Course Preoperative Chemoradiation for Locally Advanced Rectal Adenocarcinoma

Cancer Research and Treatment ◽

10.4143/crt.2017.252 ◽

2018 ◽

Vol 50 (3) ◽

pp. 1039-1050 ◽

Cited By ~ 3

Author(s):

Sea-Won Lee ◽

Jong Hoon Lee ◽

In Kyu Lee ◽

Seong Taek Oh ◽

Dae Yong Kim ◽

...

Keyword(s):

Tumor Response ◽

Locally Advanced ◽

Rectal Adenocarcinoma ◽

Preoperative Chemoradiation ◽

Surgical Timing ◽

Short Course ◽

Long Course ◽

The Impact

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Cost-Effectiveness of Short Course Radiation Therapy Versus Long-Course Chemoradiation for Locally Advanced Rectal Adenocarcinoma

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2018.06.384 ◽

2018 ◽

Vol 102 (3) ◽

pp. S160

Author(s):

A. Raldow ◽

A.B. Chen ◽

P. Lee ◽

M. Russell ◽

T.S. Hong ◽

...

Keyword(s):

Radiation Therapy ◽

Cost Effectiveness ◽

Locally Advanced ◽

Rectal Adenocarcinoma ◽

Short Course ◽

Long Course

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Phase II study of preoperative chemoradiation (CRT) with cetuximab, irinotecan and capecitabine in patients with locally advanced resectable rectal cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4045 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4045-4045 ◽

Cited By ~ 7

Author(s):

Y. S. Hong ◽

D. Y. Kim ◽

K. S. Lee ◽

S. B. Lim ◽

H. S. Choi ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Anal Verge ◽

Locally Advanced ◽

Rectal Adenocarcinoma ◽

R0 Resection ◽

Efficacy And Safety ◽

Open Label ◽

Resectable Rectal Cancer

4045 Background: Preoperative CRT with irinotecan and capecitabine is effective and safe in rectal cancer. Cetuximab, an EGFR- targeted agent, is synergistic with chemotherapy and radiotherapy. We conducted this study to determine efficacy and safety of cetuximab, irinotecan, and capecitabine as a combined preoperative CRT in patients with locally advanced resectable rectal cancer. Methods: This is a non-randomized, open-label, multicenter phase II study with cetuximab 400mg/m2 on D-6 (1 week before radiation) followed by cetuximab 250mg/m2 and irinotecan 40mg/m2 once a week (D1, 8, 15, 22, & 29) and capecitabine 1650mg/m2/day for weekdays only during radiation. Radiotherapy was given to a total dose of 50.4 Gy/28 fractions starting on D1. Main eligibility criteria were histologically proven rectal adenocarcinoma; T3–4 lesions; age 18 - 75 years; ECOG PS 0 - 2; no prior chemotherapy or EGFR targeted therapy. Total mesorectal excision was planned to be performed 4–8 weeks after completion of CRT. Results: Between May 2006 and Dec 2006, 40 patients were enrolled; median age 56.5 years (34 - 72); M/F 32/8; PS 0–1/2 38/2; cT3/T4 36/4; cN0/N+ 8/32; median tumor location from anal verge 5.5cm (0 - 8.0); moderately-differentiated adenocarcinoma 29. At present, 21 patients completed preoperative CRT and were evaluable for toxicity. Grade 3/4 toxicities included leucopenia (2, 9.5%), neutropenia (1, 4.8%), anemia (1, 4.8%) and diarrhea (1, 4.8%). Grade 2 hypersensitivity reactions and skin rashes were observed in 2 (9.5%) and 9 patients (42.9%), respectively and no grade >1 hand-foot syndrome was observed. Of 10 patients who underwent surgery (all R0 resection) till now, 9 were treated with sphincter saving procedure. Pathologic T0 and N0 were observed in 3 and 7 patients, respectively. Pathologic complete responses were observed in 2 patients and another 2 patients had only minimal microscopic residual tumor. Conclusions: Preoperative CRT with cetuximab, irinotecan and capecitabine showed promising preliminary pathologic responses with mild toxicity profiles. Study enrollment has now been completed and further results of efficacy and safety will be presented. No significant financial relationships to disclose.

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