Evidence map›Paper›PMID 36814222›Full record

Trial reportBMC cancer2023

INTEGRATE II: randomised phase III controlled trials of regorafenib containing regimens versus standard of care in refractory Advanced Gastro-Oesophageal Cancer (AGOC): a study by the Australasian Gastro-Intestinal Trials Group (AGITG).

Lyn Ley Lam, Nick Pavlakis, Kohei Shitara, Katrin M Sjoquist, Andrew J Martin, Sonia Yip, Yoon-Koo Kang, Yung-Jue Bang, Li-Tzong Chen, Markus Moehler and 14 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02773524 phase3unknown statusnot on this map

A Randomised Phase III Double-Blind Placebo-Controlled Study of Regorafenib in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

TypeinterventionalSponsorAustralasian Gastro-Intestinal Trials GroupRan2016 to 2022Enrolled250ConditionsGastro-Oesophageal CancerArmsRegorafenib, Placebo
NCT04879368 phase3completednot on this map

A Randomised Phase III Open Label Study of Regorafenib + Nivolumab vs Standard Chemotherapy in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

TypeinterventionalSponsorAustralasian Gastro-Intestinal Trials GroupRan2021 to 2025Enrolled462ConditionsGastro-Oesophageal CancerArmsRegorafenib, Nivolumab, Docetaxel, Paclitaxel, Irinotecan
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Guideline
  2. Health-related quality-of-life outcomes with regorafenib in advanced gastric and esophagogastric junction cancer: results from the INTEGRATE trials.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
    Trial
  3. Trial
  4. Trial
  5. Article
  6. Review
  7. Review
  8. Progress of immune checkpoint inhibitors in gastric cancer.World journal of gastrointestinal oncology · 2025
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 16 institutions in 7 countries.

Lyn Ley LamNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia. integrateii.study@sydney.edu.au.
Nick PavlakisRoyal North Shore Hospital, Sydney, Australia.
Kohei ShitaraNational Cancer Centre Hospital East, Chiba, Japan.
Katrin M SjoquistNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
Andrew J MartinNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
Sonia YipNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
Yoon-Koo KangAsan Medical Centre, Seoul, South Korea.
Yung-Jue BangSeoul National University College of Medicine, Seoul, South Korea.
Li-Tzong ChenCollege of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Markus MoehlerUniversity Medical Centre Mainz, Mainz, Germany.
Tanios Bekaii-SaabMayo Clinic Comprehensive Cancer Centre, Phoenix, USA.
Thierry AlcindorMcGill University Health Centre, Montreal, Canada.
Christopher J O'CallaghanOlivia Newton-John Cancer Wellness & Research Centre, Melbourne, Australia.
Niall C TebbuttOlivia Newton-John Cancer Wellness & Research Centre, Melbourne, Australia.
Wendy HagueNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
Howard ChanCalvary Mater Newcastle, Waratah, Australia.
Sun Young RhaYonsei Cancer Centre, Yonsei University Health System, Seoul, South Korea.
Keun-Wook LeeSeoul National University College of Medicine, Seoul, South Korea.
Val GebskiNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
Anthony JaworskiNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
John ZalcbergMonash University Melbourne, Melbourne, Australia.
Timothy PriceThe Queen Elizabeth Hospital, Adelaide, Australia.
John SimesNHMRC Clinical Trials Centre, University of Sydney, Camperdown, Sydney, Australia.
David GoldsteinPrince of Wales Hospital, Sydney, Australia.
National Health and Medical Research Council · AUOlivia Newton-John Cancer Wellness & Research Centre · AUSeoul National University · KRThe University of Sydney · AUAsan Medical Center · KRCalvary Mater Newcastle Hospital · AUKaohsiung Medical University · TWMayo Clinic in Arizona · USMcGill University Health Centre · CAMonash University · AUNational Cancer Centre Japan · JPPrince of Wales Hospital · AUQueen Elizabeth Hospital · AURoyal North Shore Hospital · AUUniversity Medical Center of the Johannes Gutenberg University Mainz · DEYonsei University Health System · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdvanced gastro-oesophageal cancer (AGOC) carries a poor prognosis. No standard of care treatment options are available after first and second-line therapies. Regorafenib is an oral multi-targeted tyrosine kinase inhibitor targeting angiogenic, stromal, and oncogenic receptor tyrosine kinases. Regorafenib 160 mg daily prolonged progression free survival compared to placebo (INTEGRATE, phase 2). Regorafenib 80 mg daily in combination with nivolumab 3 mg/kg showed promising objective response rates (REGONIVO). METHODS/

designINTEGRATE II (INTEGRATE IIa and IIb) platform comprises two international phase III randomised controlled trials (RCT) with 2:1 randomisation in favor of experimental intervention. INTEGRATE IIa (double-blind) compares regorafenib 160 mg daily on days 1 to 21 of each 28-day cycle to placebo. INTEGRATE IIb (open label) compares REGONIVO, regorafenib 90 mg days 1 to 21 in combination with intravenous nivolumab 240 mg days 1 and 15 each 28-day cycle with investigator's choice of chemotherapy (control). Treatment continues until disease progression or intolerable adverse events as per protocol. Eligible participants include adults with AGOC who have failed two or more lines of treatment. Stratification is by location of tumour (INTEGRATE IIa only), geographic region, prior VEGF inhibitor and prior immunotherapy use (INTEGRATE IIb only). Primary endpoint is overall survival. Secondary endpoints are progression free survival, objective response rate, quality of life, and safety. Tertiary/correlative objectives include biomarker and pharmacokinetic evaluation. DISCUSSION: INTEGRATE II provides a platform to evaluate the clinical utility of regorafenib alone, as well as regorafenib in combination with nivolumab in treatment of participants with refractory AGOC.

trial registrationINTEGRATE IIa prospectively registered 1 April 2016 Australia New Zealand Clinical Trial Registry: ACTRN12616000420448 (ClinicalTrials.gov NCT02773524). INTEGRATE IIb prospectively registered 10 May 2021 ClinicalTrials.gov: NCT04879368.

Indexed as

Esophageal NeoplasmsStomach NeoplasmsAdultAntineoplastic Combined Chemotherapy ProtocolsDouble-Blind MethodHumansNivolumabPhenylurea CompoundsPyridinesRandomized Controlled Trials as TopicNivolumabPhenylurea CompoundsPyridinesregorafenibAdvanced gastro-oesophageal cancerClinical trialNivolumabRegorafenibTyrosine kinase inhibitor

Identifiers

PMID36814222
PMCPMC9945618
OpenAlexW4321487567

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.