Roche Holding AG gains FDA approval for Tecentriq in stage III dMMR colon cancer
The Oct. 8 label covers IV treatment from age two and Hybreza injections from age 12 for patients weighing at least 40 kilograms.
Adrian Kessler
An adjuvant immunotherapy option opened for stage III dMMR colon cancer on Oct. 8 as the FDA approved Tecentriq and Tecentriq Hybreza with chemotherapy for Roche Holding AG SWXROP OTCMKTSRHHBY through its Genentech unit. The intravenous Tecentriq label covers patients aged two and older; the under-the-skin Hybreza label starts at age 12 and requires a weight of at least 40 kilograms.
Roche's U.S.-traded OTCMKTSRHHBY receipts finished at US$54.09, up 1.35 per cent, at the 4 p.m. EDT close on Oct. 9. The SIX Swiss Exchange lists ROP as Roche's participation certificate.
Genentech is Roche's South San Francisco biotechnology subsidiary. Its Tecentriq antibody blocks PD-L1, a protein that can help cancer cells evade an immune response.
The ATOMIC trial's March 25 analysis estimated three-year disease-free survival at 86.3 per cent with Tecentriq and chemotherapy, against 76.2 per cent with chemotherapy alone. Roche's next scheduled investor update is its Oct. 22 third-quarter sales presentation.
ATOMIC Met Its Disease-Free Survival Endpoint
The phase 3, open-label study enrolled 712 people with resected stage III dMMR colon cancer. The published paper credits the National Cancer Institute and Genentech as funders. Investigators assigned 355 patients to Tecentriq plus mFOLFOX6 chemotherapy and 357 to chemotherapy alone, according to the March 25 paper.
The combination arm received both drugs for six months, followed by six more months of Tecentriq; the comparison arm received six months of chemotherapy. Disease-free survival, the primary endpoint, tracked recurrence or death after surgery.
The FDA's Oct. 8 account reported a hazard ratio of 0.50 and a p-value of 0.0001. Its 95 per cent confidence interval ran from 0.35 to 0.73, while median disease-free survival had not been reached in either arm.
Grade 3 or 4 adverse events were more frequent with added Tecentriq. The March 25 paper recorded them in 84.1 per cent of the combination group, against 71.9 per cent with chemotherapy alone. The FDA said the prescribing information includes warnings and precautions for immune-mediated adverse reactions and infusion-related reactions.
Genentech estimated in its June 10 release that approximately 15 per cent of colon cancer patients have dMMR or MSI-H tumors across all stages. The U.S. approval reaches the smaller, post-surgery stage III group whose tumors show mismatch repair deficiency; the broad percentage cannot be treated as a count of eligible patients. Genentech cited immunohistochemistry, including the VENTANA MMR RxDx Panel, as a way to establish that tumor status.
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Merck's Colorectal Label Covers Advanced Disease
Merck & Co., Inc. NYSEMRK is a peer in biomarker-selected colorectal cancer treatment, but its Keytruda approval, announced June 29, 2020, covers first-line treatment of unresectable or metastatic MSI-H or dMMR disease. Roche's Oct. 8 Tecentriq decision addresses the earlier setting after resection, so the two labels do not describe the same patients.
Merck's advanced-disease label shows where immune therapy was already established for this biomarker. Roche can now offer Tecentriq before recurrence to patients who meet the narrower post-surgery criteria, with disease-free survival rather than tumor shrinkage as the ATOMIC trial's main measure.
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The Oct. 8 FDA notice said Health Canada, Swissmedic, Australia's Therapeutic Goods Administration and Israel's health ministry were reviewing the applications through Project Orbis. The U.S. decision does not itself authorize Tecentriq for this use in those countries.
"The application reviews are ongoing at the other regulatory agencies," the FDA said in its Oct. 8 approval notice.
Roche's Oct. 22 third-quarter sales presentation will provide a group sales benchmark from before the Oct. 8 U.S. approval. Later reporting periods will show whether Tecentriq's overall sales grow as the newly eligible colon cancer patients enter treatment.
