597P - Surgical quality for patients (pts) treated with neoadjuvant chemotherapy vs chemoradiation for locally advanced rectal cancer (LARC): PROSPECT (NCCTG N1048, alliance)

Background

Radiation with sensitizing fluoropyrimidine (5FUCRT) is a standard curative intent treatment for LARC. The PROSPECT trial compared FOLFOX chemotherapy with selective use of 5FUCRT (intervention) to 5FUCRT (control) for neoadjuvant treatment prior to total mesorectal excision (TME) for LARC and the primary endpoint of non-inferiority disease-free survival was met. Analyzing quality of surgery is key to interpreting the results of PROSPECT.

Methods

Trial eligibility included cT2N+, cT3N-, cT3N+ rectal cancers deemed appropriate for neoadjuvant therapy prior to TME. Exclusions included tumors not amenable to sphincter preservation, T4 disease, threatened radial margins, or > 4 enlarged lymph nodes. Pts were randomized 1:1 to 5FUCRT with 5040 cGy over 5.5 weeks with capecitabine or 5FU (control) or 6 cycles of mFOLFOX6 (intervention) followed by restaging. Secondary and post hoc surgical quality endpoints included: rate of sphincter preservation, completeness of TME, number of lymph nodes examined, radial margin status, length of hospital stay, reoperation, readmission, and rate of ostomy formation.

Results

From 6/2012 to 12/2018, 1194 pts were randomized, 1128 initiated protocol-assigned treatment, and 1045 completed surgery. Median age was 57 years, 34.4% were women, 61.9% had clinically positive nodes, 78.9% of tumors were <10 cm from the anal verge with a median tumor height of 8 cm. The table shows surgical quality outcomes.

Table: 597P

¹Chi-Square; ²Kruskal-Wallis

Conclusions

Low rate of positive radial margin along with high rate of complete/near complete TME and number of lymph nodes examined demonstrate a high quality of surgery in this multicenter trial. More pts treated with 5FUCRT (relative to the FOLFOX arm) required an ostomy and readmission within 30 days of surgery.

Clinical trial identification

NCT01515787. U 10CA180821, U10CA180882; U10CA180863 and CCS 707213 (CCTG); U10CA180820 (ECOG-ACRIN); UG1CA189867 and U10CA180868 (NRG Oncology); U10CA180888 (SWOG).

Editorial acknowledgement

Legal entity responsible for the study

Alliance.

Funding

Support: U10CA180821, U10CA180882.

Disclosure

Q. Shi: Financial Interests, Personal, Advisory Board: Regeneron Pharmaceuticals, Inc., Kronos Bio; Financial Interests, Personal, Advisory Board, DSMB: Hoosier Cancer Research Network, Yiviva Inc., Mirati Therapeutics Inc; Financial Interests, Institutional, Research Grant: Genentech, Bristol Myers Squibb, Novartis, Johnson & Johnson. J. Goldberg: Financial Interests, Personal, Advisory Board: LM Education and Exchange Services, LLC, Institute of Surgical Excellence, Noble Insights; Financial Interests, Personal, Research Funding: Genentech. M. Gollub: Financial Interests, Personal, Advisory Board: GSK. B.L. Musher: Financial Interests, Personal, Research Funding: Lokon Pharma, Merck. T. George: Financial Interests, Personal, Advisory Board: Pfizer, Array, Tempus, BilliontoOne. E.M. O'Reilly: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, BioNTech, Merck, AstraZeneca, Novartis, Fibrogen, Astellas, Tempus, Merus, Bristol Myers Squibb, Berry Genomics, Exelixis, Incyte, Helio, Neogene, Newbridge, QED, Sevier, Thetis, Vector, Yiviva; Financial Interests, Personal, Advisory Board, +Spouse: Ipsen; Financial Interests, Personal, Advisory Board, Spouse: Genentech/Roche, Eisai; Financial Interests, Personal, Advisory Board, + spouse: Autem; Financial Interests, Institutional, Local PI: Genentech/Roche, Arcus, Elicio; Financial Interests, Personal and Institutional, Coordinating PI: BioNTech; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Pertzye; Financial Interests, Institutional, Research Grant: Parker Institute for Cancer Immunotherapy; Non-Financial Interests, Other, Scientific and Medical Advisory Board: Pancreas Cancer Action Network; Non-Financial Interests, Member of Board of Directors: National Pancreas Foundation; Other, Editor: American Society of Clinical Oncology, American Association of Cancer Research (AACR); Other, Advisor/no compensation: Thetis, BioSapien. J. Meyerhardt, H. Mamon: Financial Interests, Personal, Advisory Board: Merck. D. Schrag: Financial Interests, Personal, Research Funding: GRAIL; Financial Interests, Personal, Stocks or ownership: Merck; Financial Interests, Personal, Royalties: JAMAA. All other authors have declared no conflicts of interest.