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When an EGFR antibody stops working, the resistant cells that caused it fade away once the drug is withdrawn. Rechallenge means giving the same class of drug again later, after a blood test has confirmed those resistant clones have receded, and in small trials about a fifth to a third of patients respond a second time.
The idea. Resistance to cetuximab and panitumumab is driven by clones carrying mutations in RAS, BRAF or the EGFR extracellular domain. Those clones are outcompeted once the selective pressure is removed, and the mutant alleles fall away in circulating tumour DNA during a chemotherapy-free interval, which suggests the tumour can be made sensitive again.
The trials. CRICKET gave cetuximab and irinotecan as third-line treatment to 28 patients with RAS and BRAF wild-type disease who had responded to and then progressed on a first-line irinotecan and cetuximab regimen: six partial responses (four confirmed) and nine stabilisations, a response rate of 21 percent and a disease control rate of 54 percent. RAS mutations were found in the blood at the time of rechallenge in 12 of 25 evaluable patients, none of the confirmed responders carried one, and patients whose circulating tumour DNA was RAS wild-type had longer progression-free survival (4.0 against 1.9 months, hazard ratio 0.44) (Cremolini 2019). CHRONOS made that selection the design rather than an afterthought: 52 patients with tissue RAS wild-type tumours previously treated with an EGFR antibody were screened by circulating tumour DNA, 16 (31 percent) were excluded for carrying a resistance mutation, and of the 27 enrolled and given chemotherapy-free panitumumab, eight (30 percent) had a partial response and 17 (63 percent) disease control (Sartore-Bianchi 2022).
Where it stands. Both trials are single-arm phase 2. No randomised comparison against standard later-line treatment has reported, so rechallenge is a reasonable option in the right patient rather than a standard, and the parent record lists it among the open problems. What the trials have established is narrower and solid: an interventional blood test can be turned round in time to choose the treatment, and it changes who is offered it.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Showing the target this term concerns: EGFR.
Shares Sidedness (left vs right colon), BRAF, EGFR, KRAS and the tags gi, colorectal.
Shares Extended RAS testing, Sidedness (left vs right colon), Colon cancer (adenocarcinoma of the colon), Rectal cancer and the tags gi, colorectal.
Shares Sidedness (left vs right colon), Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares Sidedness (left vs right colon), BRAF, Colon cancer (adenocarcinoma of the colon), Colorectal cancer and the tags gi, colorectal.
Shares Circulating tumour DNA (ctDNA), Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.
Shares Colon cancer (adenocarcinoma of the colon), Rectal cancer, Colorectal cancer and the tags gi, colorectal.