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The first trial to let a blood test decide whether to give an EGFR antibody a second time. A third of the patients screened had resistance mutations and were excluded; of those rechallenged, three in ten responded.
Resistance to EGFR antibodies in colorectal cancer arises through RAS, BRAF and EGFR ectodomain mutant clones that expand under treatment and then decline once the drug is withdrawn, which raises the possibility of rechallenging the same tumour later. CHRONOS was an open-label, single-arm phase 2 trial that tested this prospectively: patients whose tissue was RAS wild-type and who had already progressed on an EGFR-based regimen had an interventional circulating tumour DNA screen, and only those without a detectable RAS, BRAF or EGFR resistance mutation were rechallenged with chemotherapy-free panitumumab. Of 52 patients screened, 16 (31 percent) carried at least one resistance mutation and were excluded. Of the 27 enrolled, eight (30 percent) achieved a partial response, including two unconfirmed responses, and 17 (63 percent) had disease control. The primary endpoint was met. These figures compare favourably with standard third-line treatment, and CHRONOS is the proof that a liquid biopsy can be used interventionally, to choose treatment rather than to describe a tumour. It is small and single-arm, so anti-EGFR rechallenge remains unproven in phase 3.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
Shares Panitumumab, BRAF, Circulating tumour DNA (ctDNA), EGFR.
Shares BRAF, EGFR, KRAS, Liquid biopsy (ctDNA).
Shares NRAS, BRAF, Circulating tumour DNA (ctDNA), EGFR.
Shares NRAS, Panitumumab, BRAF, EGFR.
Shares NRAS, Panitumumab, BRAF, EGFR.
Shares Panitumumab, Circulating tumour DNA (ctDNA), EGFR, KRAS.
Shares NRAS, Panitumumab, EGFR, KRAS.
Shares NRAS, EGFR, KRAS, Colorectal cancer.