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Clinical Trial
. 2021 Sep 1;39(25):2803-2815.
doi: 10.1200/JCO.20.03611. Epub 2021 Jun 2.

Randomized Phase II Study of PET Response-Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial

Karyn A Goodman  1 , Fang-Shu Ou  2 , Nathan C Hall  3 , Tanios Bekaii-Saab  4 , Briant Fruth  2 , Erin Twohy  2 , Michael O Meyers  5 , Daniel J Boffa  6 , Kisha Mitchell  7 , Wendy L Frankel  8 , Donna Niedzwiecki  9 , Anne Noonan  8 , Yelena Y Janjigian  10 , Paul J Thurmes  11 , Alan P Venook  12 , Jeffrey A Meyerhardt  13 , Eileen M O'Reilly  10 , David H Ilson  10
Affiliations
Clinical Trial

Randomized Phase II Study of PET Response-Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial

Karyn A Goodman et al. J Clin Oncol. .

Abstract

Purpose: To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma.

Methods: After baseline PET, patients were randomly assigned to an induction chemotherapy regimen: modified oxaliplatin, leucovorin, and fluorouracil (FOLFOX) or carboplatin-paclitaxel (CP). Repeat PET was performed after induction; change in maximum standardized uptake value (SUV) from baseline was assessed. PET nonresponders (< 35% decrease in SUV) crossed over to the alternative chemotherapy during chemoradiation (50.4 Gy/28 fractions). PET responders (≥ 35% decrease in SUV) continued on the same chemotherapy during chemoradiation. Patients underwent surgery at 6 weeks postchemoradiation. Primary end point was pathologic complete response (pCR) rate in nonresponders after switching chemotherapy.

Results: Two hundred forty-one eligible patients received Protocol treatment, of whom 225 had an evaluable repeat PET. The pCR rates for PET nonresponders after induction FOLFOX who crossed over to CP (n = 39) or after induction CP who changed to FOLFOX (n = 50) was 18.0% (95% CI, 7.5 to 33.5) and 20% (95% CI, 10 to 33.7), respectively. The pCR rate in responders who received induction FOLFOX was 40.3% (95% CI, 28.9 to 52.5) and 14.1% (95% CI, 6.6 to 25.0) in responders to CP. With a median follow-up of 5.2 years, median overall survival was 48.8 months (95% CI, 33.2 months to not estimable) for PET responders and 27.4 months (95% CI, 19.4 months to not estimable) for nonresponders. For induction FOLFOX patients who were PET responders, median survival was not reached.

Conclusion: Early response assessment using PET imaging as a biomarker to individualize therapy for patients with esophageal and esophagogastric junction adenocarcinoma was effective, improving pCR rates in PET nonresponders. PET responders to induction FOLFOX who continued on FOLFOX during chemoradiation achieved a promising 5-year overall survival of 53%.

Trial registration: ClinicalTrials.gov NCT01333033.

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Conflict of interest statement

Karyn A. GoodmanConsulting or Advisory Role: RenovoRx Tanios Bekaii-SaabConsulting or Advisory Role: Amgen, Ipsen, Lilly, Bayer, Roche/Genentech, AbbVie, Incyte, Immuneering, Seattle Genetics, Pfizer, Boehringer Ingelheim, Janssen, Eisai, Daiichi Sankyo/UCB Japan, AstraZeneca, Exact Sciences, Natera, Treos Bio, Celularity, SOBI, BeiGene, Foundation MedicinePatents, Royalties, Other Intellectual Property: Patent WO/2018/183488 and Patent WO/2019/055687Other Relationship: Exelixis, Merck, AstraZeneca, Lilly, Pancreatic Cancer Action Network Daniel J. BoffaResearch Funding: Epic Sciences Wendy L. FrankelPatents, Royalties, Other Intellectual Property: Patent title: Automated Identification of Tumor Buds. Application No.: 16/230,118. Filing date: December 21, 2018. Publication date: July 4, 2019. Applicant(s): Ohio State Innovation Foundation, Columbus, OH. Inventor(s): Metin Gurcan, Winston-Salem, NC; Wendy Frankel, Columbus, OH; Wei Chen, Columbus, OH; Ahmad Fauzi and Mohammad Faizal, Selangor, MY Anne NoonanConsulting or Advisory Role: Helsinn Healthcare, QED Therapeutics, Exelixis, Eisai Yelena Y. JanjigianStock and Other Ownership Interests: RgenixConsulting or Advisory Role: Pfizer, Merck, Bristol Myers Squibb, Merck Serono, Daiichi Sankyo, Rgenix, Bayer, Imugene, AstraZeneca, Lilly, Zymeworks, Seattle Genetics, Merck Sharpe and Dohme Corp, Michael J. Hennessy Associates, Jounce Therapeutics, Ono PharmaceuticalResearch Funding: Boehringer Ingelheim, Bayer, Roche, Genentech, Rgenix, Bristol Myers Squibb, Merck, LillyOther Relationship: Paradigm, Clinical Care Options, Axis Medical Education, Research to Practice Paul J. ThurmesConsulting or Advisory Role: US OncologyTravel, Accommodations, Expenses: US Oncology Alan P. VenookConsulting or Advisory Role: Merck Sharp & Dohme, Array BioPharmaResearch Funding: Genentech/Roche, Bristol Myers Squibb, AmgenPatents, Royalties, Other Intellectual Property: Royalties from Now-UptoDate for authoring and maintaining two chaptersTravel, Accommodations, Expenses: Genentech, Roche Jeffrey A. MeyerhardtHonoraria: Cota Healthcare, Taiho PharmaceuticalResearch Funding: Boston Biomedical Eileen M. O'ReillyConsulting or Advisory Role: Merck, Agios, AstraZeneca, Bayer, BeiGene, Berry Genomics, Celgene, CytomX Therapeutics, Debiopharm Group, Eisai, Exelixis/Ipsen, Flatiron Health, Incyte, Janssen, LAM Therapeutics, Lilly, Loxo, Genentech/Roche, Minapharma, QED Therapeutics, RedHill Biopharma, Sillajen, SOBI, Yiviva, Autem Medical, Gilead Sciences, Ipsen, Silenseed, TheraBionic, twoXAR, Vector HealthResearch Funding: AstraZeneca/MedImmune, Acta Biologica, Bristol Myers Squibb, Celgene, Genentech, Halozyme, MabVax, Roche, Silenseed David H. IlsonConsulting or Advisory Role: Lilly/ImClone, Roche/Genentech, Bristol Myers Squibb, Pieris Pharmaceuticals, Merck, Bayer, AstraZeneca, Taiho Pharmaceutical, Astellas Pharma, IQvia, MacrogenicsNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
CONSORT diagram. aAll 225 patients received induction chemotherapy; bReceived FOLFOX as the chemotherapy. The induction chemotherapy and PET response groups with zero counts have been grayed out. CP, carboplatin-paclitaxel; FF, FOLFOX (modified oxaliplatin, leucovorin, and fluorouracil); PET, positron emission tomography.
FIG 2.
FIG 2.
(A) OS by PET response after induction chemotherapy. (B) OS by induction chemotherapy and PET response groups (four groups). aKaplan-Meier method; bCox model; cLog-rank test. CP, carboplatin-paclitaxel; FOLFOX, modified oxaliplatin, leucovorin, and fluorouracil; NE, not estimable; OS, overall survival; PET, positron emission tomography.
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