FDA Broadens Lonsurf Use in Colorectal Cancer

Reprinted with AIS Health permission from the September 2023 issue of Radar on Specialty Pharmacy

The FDA recently granted another approval to Taiho Pharmaceutical Co., Ltd. Division Taiho Oncology, Inc.’s Lonsurf (trifluridine/tipiracil) in combination with another agent for a type of colorectal cancer. The decision provides another treatment option for a condition that respondents to a Zitter Insights survey regard as in need of more effective therapies.

On Aug. 2, the FDA approved Lonsurf as a single agent or in combination with bevacizumab for the treatment of adults with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) drug and, if Rat sarcoma (RAS) wild-type, an anti-epidermal growth factor receptor (EGFR) therapy. Bevacizumab originally was available as Avastin from Genentech USA, Inc., a member of the Roche Group, but now four biosimilars of it are also on the market: Celltrion USA, Inc.’s Vegzelma (bevacizumab-adcd), Amneal Pharmaceuticals, Inc.’s Alymsys (bevacizumab-maly), Pfizer Inc.’s Zirabev (bevacizumab-bvzr) and Amgen Inc.’s Mvasi (bevacizumab-awwb).

The agency first approved the oral nucleoside antitumor agent for use as a monotherapy for the indication on Sept. 22, 2015.

It also is approved for the treatment of adults with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, human epidermal growth factor receptor 2 (HER2)/neu-targeted therapy.

The newest use had priority review. Dosing for the tablet is 35 mg/m2 twice daily on days one through five and days eight through 12 of each 28-day cycle. Drugs.com lists the price of 20 6.14 mg/15 mg tablets as more than $4,204.

For the Managed Care Oncology Index: Q4 2022, from Nov. 21, 2022, to Dec. 22, 2022, Zitter Insights polled 34 commercial payers covering 120.8 million lives, 25 Medicare payers representing 40.5 million lives and 100 oncologists about their management and prescribing of colorectal cancer therapies. Commercial payers with 85% of lives, Medicare payers with 40% of lives and 56% of oncologists expressed average satisfaction with current treatments. No payers and only 4% of oncologists said they were extremely satisfied with the available options.

Both AIS Health and Zitter Insights are divisions of MMIT.

Payers varied somewhat in the level of aggressiveness in managing branded products for colorectal cancer, although those with 41% of commercial beneficiaries and 46% of Medicare lives said their approach was slightly aggressive. Payers with 65% of commercial lives and 87% of Medicare lives rated managing branded treatments for the condition as a high priority (see chart).


Payers with the most lives said that agents to treat the disease have an average to high impact on their budget. Respondents covering almost all Medicare beneficiaries said that there is a high or very high disease burden for people with the disease.

Regimen May Improve Survival

According to Marwan Fakih, M.D., a professor in the department of medical oncology and therapeutics research at City of Hope and the lead U.S. investigator for the Phase 3 SUNLIGHT trial that evaluated this new use, the approval gives people with metastatic colorectal cancer “an important new treatment option, one that has been shown to extend life in addition to other benefits and which I believe will change the treatment landscape for this patient population.” He added that Lonsurf plus bevacizumab “did not result in an increase in potentially intolerable side effects that might limit the utility of this combination.”

The new regimen may help improve the survival of some people with metastatic colorectal cancer, agrees Andy Szczotka, Pharm.D., chief pharmacy officer at AscellaHealth. He tells AIS Health that while both bevacizumab and Lonsurf already had FDA approval as monotherapies to treat colorectal cancer, “this new combination of therapies increased the median survival and progression free survival. The SUNLIGHT trial included 492 patients with mCRC [metastatic colorectal cancer] who had received two or less previous chemotherapy regimens and had progressive disease or had intolerance to the last regimen.”

The SUNLIGHT trial results showed that the combination regimen “provided statistically significant and clinically meaningful improvements in overall survival and progression-free survival in patients with metastatic colorectal cancer following disease progression or intolerance on two prior chemotherapy regimens compared to Lonsurf alone. Patients who received Lonsurf plus bevacizumab lived a median of 10.8 months compared to 7.5 months for those on Lonsurf alone, an approximate 39% reduction.”

With respect to progression-free survival (PFS) — the length of time people lived without their cancer getting worse — the two drugs increased it by a median of 5.6 months vs. 2.4 months on Lonsurf alone, he adds.

In addition, says Szczotka, that trial “was the first Phase III study involving patients with mCRC to demonstrate an overall survival (OS) as compared to an existing therapy regimen. This may help pave a pathway for a potential new standard of care for patients that have not responded to prior recommended treatment regimens, including Lonsurf.” He also notes that the new regimen “seemed to be effective regardless of whether the tumor had a RAS mutation, which may add to applicability of this new treatment option.”

However, he points out that while the new regimen “is a potential therapy enhancement, the drug cost for each treatment cycle for this combination treatment regimen is approximately $21,000 to $23,000 (depending on the choice of bevacizumab) or $273,000 to $300,000 annually.”

As far as potential competitors for the new regimen, Bayer’s Stivarga (regorafenib) — a “multikinase inhibitor that is active against several angiogenic receptor tyrosine kinases, oncogenic RTKs, stromal RTKs and intracellular signaling kinases — is also used in people who have progressed through all other treatment options, he says.

“Stivarga can be given either before or after Lonsurf, [and] no data inform the best order of these therapies, although real-world data have shown that patients show better adherence to” Lonsurf compared with Stivarga, explains Szczotka. He notes that the two agents had similar efficacy in their pivotal trials: Lonsurf with a median OS of 7.2 months and Stivarga with a median OS of 6.4 months. “With the new data, the combination of Lonsurf and bevacizumab boosts that median OS to 10.8 months, which may provide a potential advantage as compared to Stivarga. A prior published 2020 study in Japan comparing the real-world efficacy and safety of Lonsurf to regorafenib in patients with mCRC refractory to standard chemotherapies showed that the median PFS was 3.3 and 2.0 months with Lonsurf to Stivarga, respectively (hazard ratio = 0.52, p = 0.00047), indicating a potential difference, whereas the objective response and disease control rates did not differ.”

Asked if metastatic colorectal cancer is a priority for payers to manage, Szczotka says that the World Health Organization is projecting a global rise in colorectal cancer cases of about 79% through 2030.

“While oncology management is a priority for payers, other cancers with higher prevalence typically are a higher priority for payers (e.g., breast, lung, prostate),” he states. “While colon cancer is also in the higher rate of incidence as compared to other cancer types, due to the high cost of mCRC therapies, payers typically will be working to ensuring appropriate management with this class of therapies.”

For more information on the Zitter Insights data, contact Jill Brown Kettler at jkettler@mmitnetwork.com. Contact Szczotka via Caroline Chambers at cchambers@cpronline.com.

By Angela Maas

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