Lonsurf and Bevacizumab Receive FDA Approval for 3rd-Line Treatment of Metastatic Colorectal Cancer

Colorectal cancer is the 3rd most common cancer worldwide in both men and women, and treatment options are often limited when it is diagnosed at an advanced stage. Finding new and more effective treatments is therefore vital. Against this backdrop, the FDA's (US Food and Drug Administration) approval of a new treatment combination is a promising development.

On August 2, 2023, the FDA approved a combination for metastatic (stage 4) colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, anti-VEGF biological therapy and, if RAS wild-type, anti-EGFR therapy. The combination consists of trifluridine/tipiracil (LONSURF, Taiho Oncology, Inc.) and bevacizumab .

The FDA had approved Lonsurf, containing trifluridine/tipiracil, as monotherapy for metastatic disease in 2015. Trifluridine/tipiracil also has FDA approval for metastatic gastric or gastroesophageal junction adenocarcinoma after at least two previous lines of treatment. However, the drug has not yet received marketing authorization from Turkey's Ministry of Health. To use it in Turkey, off-label authorization must be obtained from the Ministry of Health, and it must be supplied through the Turkish Pharmacists' Association (TEB).

What Is Trifluridine/Tipiracil and How Does It Work?

Trifluridine/tipiracil, marketed as LONSURF, is an oral chemotherapy drug used to treat certain advanced cancers, including metastatic colorectal and gastric cancer. It is generally used as a subsequent treatment option in patients whose disease did not respond to other therapies or became resistant to them.

Trifluridine/tipiracil contains two active ingredients: trifluridine and tipiracil. Together, they improve the drug's effectiveness and inhibit the growth and proliferation of cancer cells.

Trifluridine is a nucleoside analog that prevents cancer cells from copying their DNA and therefore multiplying. However, it is rapidly broken down in the body, reducing its effectiveness.

This is where tipiracil comes in. It is a thymidine phosphorylase inhibitor that slows the breakdown of trifluridine in the body, allowing it to remain active longer and act on cancer cells for a longer period.

By inhibiting cancer cell growth and proliferation, this combination aims to prolong survival and relieve disease symptoms. However, the effectiveness and adverse effects of trifluridine/tipiracil can vary between patients, so an oncologist should assess treatment individually.

FDA Approval Based on the SUNLIGHT Clinical Trial

Approval of trifluridine/tipiracil combined with bevacizumab was based on the SUNLIGHT clinical trial. This important study was presented on January 21 at the 2023 Gastrointestinal Cancers Symposium(2023 ASCO GICS) . We shared its details in this article .

The trial compared the combination with trifluridine/tipiracil alone in 492 patients with metastatic CRC who could not tolerate their latest treatment or whose cancer had progressed after no more than two previous chemotherapy regimens.

Table 1. Summary of Baseline Participant Characteristics

• At 6 months, overall survival rates were 77% with combination therapy and 61% with the control treatment. At 12 months, the rates were 43% and 30%, respectively.
• Median progression-free survival was 5.6 months in the combination arm versus 2.4 months in the control arm (HR, 0.44; P < 0.001). Progression-free survival at 6 months was 43% versus 16%, and at 12 months it was 16% versus 1%, respectively.

Table 2. Summary of Overall and Progression-Free Survival

Regarding adverse effects , no treatment-related deaths were reported, and serious adverse-event rates were similar in both groups. Overall, adverse effects were comparable, except for somewhat higher rates of hypertension (10% versus 2%), nausea (37% versus 27%) and neutropenia (62% versus 51%) in the bevacizumab plus Lonsurf arm.

The recommended dose of trifluridine/tipiracil is 35 mg/m2 orally twice daily with food on days 1-5 and 8-12 of each 28-day cycle.

Table 3. Lonsurf Starting Dose Schedule