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PET-Guided Therapy Switch for Esophageal Cancer

<ѻý class="mpt-content-deck">— Improved response with switch from ineffective treatment
MedpageToday

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SAN FRANCISCO -- Use of PET imaging to monitor treatment -- and switch from ineffective therapy -- led to more than a fourfold improvement in pathologic complete response (pCR) for patients with esophageal cancer, a randomized trial showed.

Patients who switched to a different chemotherapy regimen on the basis of a negative PET scan had a pCR rate of 18%. That compared with a historical pCR rate of 5% for patients treated with ineffective therapy.

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • This study suggests that a PET scan-based approach to neoadjuvant chemotherapy in gastroesophageal cancer may improve outcomes.
  • Be aware that outcomes in this study were compared to historical controls.

The PET-guided strategy delays the time to surgery by the addition of another round of chemotherapy before standard chemoradiation, but investigators believe that a chance to improve a patient's odds of attaining pCR is worth the wait, as reported at the (GiCS).

"The trial results show the benefit of a new paradigm of using metabolic imaging in esophageal and gastroesophageal juncture (GEJ) cancer to individualize multimodality therapy and improve outcomes in this poor-prognosis population," , of the University of Colorado Cancer Center in Aurora, said during a press briefing prior to Thursday's start of GiCS. "Early response assessment using PET imaging can be incorporated into future studies to identify more effective new regimens for esophageal and GEJ cancers."

The study represents a step forward in the search for more personalized and effective treatment for patients with these difficult cancers, said press briefing moderator , of St. Michael's Hospital and the University of Toronto.

"PET scans may prove to be a valuable tool to help oncologists fine tune the use of chemotherapy for esophageal cancer and maximize the benefit of chemotherapy for each individual patient," said Baxter, a scientific expert for the American Society of Clinical Oncology, co-sponsor of GiCS. "This is heartening evidence for a new approach to treating a disease where innovation is sorely needed."

Preoperative chemoradiation is standard of care for patients with operable esophageal or GEJ cancer, but even with effective treatment, 5-year survival is 50% or less. Most patients die of systemic disease, and ongoing research in the field focuses on identifying more effective systemic therapies to optimize treatment. Evaluation of those therapies would benefit from better ways to identify them, said Goodman.

Several PET-based strategies to improve outcomes in esophageal and GEJ cancer have been evaluated over the years. Investigators postchemoradiation PET imaging results and subsequent outcomes. The results showed a complete response by PET had a significant association with improved 2-year overall survival and freedom from local failure for patients who received only chemoradiation, but not those who had chemoradiation followed by surgery.

A demonstrated the feasibility of using PET to determine response to induction chemotherapy and to discontinue treatment early when patients do not respond, and confirmed that a negative posttreatment PET scan identified patients with a poor prognosis.

Goodman reported findings from the Cancer and Leukemia Group B (now the Alliance for Clinical Trials in Oncology) 80803 trial, which evaluated early PET assessment of response to induction chemotherapy in patients with esophageal and GEJ cancers.

The trial involved 257 patients with stage T3/4 or N1 disease determined by pretreatment PET scan. They were randomized to two different chemotherapy regimens ( or carboplatin/paclitaxel), followed by another PET scan at 36 to 42 days.

Patients who responded to treatment by PET criteria (≥35% decrease in SUV) continued with the same chemotherapy regimen during standard chemoradiation therapy. Those who did not respond to assigned therapy were switched to the alternative regimen for chemoradiation.

The primary objective was to improve the pCR in nonresponders to induction therapy from the 5% historical rate to 20% with the PET-guided strategy.

Goodman reported that 57% of evaluable patients assigned to FOLFOX6 induction had a PET response, and 30% did not. In the carboplatin/paclitaxel arm, 50% of patients met PET response criteria and 38% did not.

Subsequent pCR rates among patients who continued randomized therapy during chemoradiation (responders) were 31.0% in the FOLFOX6 arm and 12.5% in the carboplatin/paclitaxel group. Among patients who did not respond to randomized therapy and were switched to the alternate regimen, pCR rates were 19.% in the FOLFOX6 group and 17.0% in the carboplatin/paclitaxel group.

The pCR rate for all PET nonresponders combined was 18.0%. The 95% confidence intervals (10%-28%) included the 20% prespecified goal, meaning the study met its primary endpoint. The efficacy criteria were met in both of the inductions arms, said Goodman.

Patients who met PET response criteria after induction therapy (both arms combined) had a pCR rate of 26%, and the pCR rate for the entire study population was 22.7%.

  • author['full_name']

    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined ѻý in 2007.

Disclosures

Goodman disclosed a relationship with Pfizer. One or more co-investigators disclosed relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Genentech/Roche, Lilly, Merrimack, Pfizer, Research to Practice, Sirtex Medical, Taiho Pharmaceutical, Exelixis, Merck, Polaris, GlaxoSmithKline, Lilly, Onyx, UptoDate, Halozyme, Merck Serono, Vertex, Arduro Biotech, Astellas Pharma, Celsion, Cipla, Gilead Sciences, Hexal, IntegraGen, Jennerex, MedImmune, Novartis, Pharmacyclics, Silenseed, Vicus Therapeutics, Clovis Oncology, Immunomedics, Incyte, Momenta Pharmaceuticals, Myriad Genetics, OncoMed, Sanofi, and ImClone.

Primary Source

Gastrointestinal Cancers Symposium

Goodman KA, et al "Initial results of CALGB 80803 (Alliance): A randomized phase II trial of PET scan-directed combined-modality therapy for esophageal cancer" GiCS 2017; Abstract 1.