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Dr. Fakih Video Transcript

[00:00 - 01:27] Important Safety Information

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LONSURF^® (trifluridine and tipiracil) tablets logo

Importance of timely intervention in patients with refractory mCRC

Indications and Important Safety Information

INDICATIONS

LONSURF is indicated as a single agent or in combination with bevacizumab for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe Myelosuppression: In the 1114 patients who received LONSURF as a single agent, LONSURF caused severe or life-threatening myelosuppression (Grade 3-4) consisting of neutropenia (38%), anemia (17%), thrombocytopenia (4%) and febrile neutropenia (3%). Three patients (0.3%) died due to neutropenic infection/sepsis; four other patients (0.5%) died due to septic shock.

A total of 14% of patients received granulocyte-colony stimulating factors. In the 246 patients who received LONSURF in combination with bevacizumab, LONSURF caused severe or life-threatening myelosuppression (Grade 3-4) consisting of neutropenia (52%), anemia (5%), thrombocytopenia (4%) and febrile neutropenia (0.4%).

Please see additional Important Safety Information throughout this video and full Prescribing Information at LONSURF.com/PI.

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[01:27 - 01:37] Speaker Introduction

My name is Marwan G. Fakih. I'm a medical oncologist, and I focus on gastrointestinal cancers, specifically colorectal cancer. I practice at City of Hope in Duarte, California.

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[01:38 - 02:37] Why is it important for patients with metastatic colorectal cancer to make a timely transition to third-line treatment?

Over and over again, studies show that patients who benefit from systemic therapy benefit the most if they have an ECOG performance status of 0 to 1. In our patients who are receiving second-line therapy, we perform imaging studies on an every-2-months basis.

The main reason for that is that you want to know if the treatment is working, and you want to stop a treatment that is not effective any longer as soon as possible.

Now this provides us with the opportunity to start on a third-line therapy immediately at the time of progression when the patient is still maintaining a good performance status. If we wait until a patient not only has exhausted therapy but has gone through continuation of treatment beyond progression on a second-line treatment and wait until that patient has deteriorated, we may not derive the same benefit.

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[02:37 - 03:11] What is your approach to 3L mCRC treatment?

In the management of my patients with metastatic colorectal cancer who are ready to proceed with a third-line therapy, I often choose LONSURF and bevacizumab. And the reason for choosing LONSURF and bevacizumab is really based on Level 1 evidence from a large Phase 3 randomized clinical trial that showed that LONSURF and bevacizumab is superior to a monotherapy active comparator, namely LONSURF.

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[03:11 - 05:01] How would you describe the SUNLIGHT trial and its key efficacy outcomes?

The SUNLIGHT trial is a Phase 3 randomized clinical trial that enrolled patients with metastatic colorectal cancer who had progressed on no more than 2 prior lines of therapies that included oxaliplatin, a fluoropyrimidine, irinotecan, an anti-EGFR therapy, if indicated, as well as bevacizumab. Patients were randomized to receive LONSURF + bevacizumab or LONSURF monotherapy in a 1-to-1 fashion.

The SUNLIGHT clinical trial met its primary endpoint of overall survival...

with an overall survival of 10.8 months in the LONSURF + bevacizumab arm vs 7.5 months in the LONSURF monotherapy arm.

The SUNLIGHT trial also showed an improvement in progression-free survival. The median progression-free survival with LONSURF and bevacizumab was 5.6 months vs 2.4 months for LONSURF monotherapy. This translated in a 56% prolongation in progression-free survival.

LONSURF and bevacizumab resulted in a 77% disease control rate. This again compared favorably to LONSURF monotherapy where the disease control rate was 47%.

In addition to the improvement in disease control rate, LONSURF and bevacizumab resulted in a prolongation to the time to deterioration in ECOG performance status. The time to deterioration to an ECOG performance status of 2 and above was a median of 9.3 months for LONSURF + bevacizumab vs 6.3 months for LONSURF monotherapy. This translated in a 46% improvement in the time to deterioration in favor of LONSURF and bevacizumab.

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[05:01 - 05:53] How have your patients generally tolerated LONSURF + bevacizumab, and how do you address its side effects?

The most common side effects that I see in my patients include fatigue, mild nausea, and occasionally mild diarrhea. The majority of these side effects are Grade 1 or sometimes Grade 2 in nature. In addition, I monitor them closely with laboratory testing. It is important to note that neutropenia can be seen quite often in patients receiving LONSURF + bevacizumab, but this is typically an asymptomatic adverse event, but it still needs to be addressed either with the use of growth factors or possibly with dose modifications.

I would defer you to LONSURFHCP.com website for further directions related to dose delays and dose modifications.

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[05:53 - 07:08] In short, why would you recommend LONSURF + bevacizumab in 3L mCRC?

The SUNLIGHT clinical trial provides Level 1 evidence that LONSURF + bevacizumab improves overall survival, progression-free survival, and time to deterioration in ECOG performance status when compared to an active treatment, namely LONSURF monotherapy. These data are not only statistically significant, but they are also clinically meaningful for our patients. Effective third-line therapy is important as an option for our patients. Patients receiving second-line therapy should be evaluated repeatedly, at least on an every 2- to 3-months basis, in my opinion, to assess for benefit from ongoing therapy at the time of disease progression in the second-line therapy.

We need to consider and initiate third-line therapy sooner rather than later so that we do not miss the window for intervention, especially when the patient has a good performance status and benefits the most from a third-line treatment.

See 3L mCRC in a different light—explore the SUNLIGHT data at LONSURFhcp.com.

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[07:08 - 11:18] IMPORTANT SAFETY INFORMATION (Continued) and Closing

Severe Myelosuppression: One patient (0.4%) died due to abdominal sepsis and two other patients (0.8%) died due to septic shock. A total of 29% of patients received granulocyte-colony stimulating factors. Obtain complete blood counts prior to and on Day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for severe myelosuppression and resume at the next lower dosage.

Embryo-Fetal Toxicity: LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the final dose.

USE IN SPECIFIC POPULATIONS

Lactation: It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LONSURF and for 1 day following the final dose.

Male Contraception: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use: Patients 65 years of age or older who received LONSURF as a single agent had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (20% vs 14%), and Grade 3 or 4 thrombocytopenia (6% vs 3%). Patients 65 years of age or older who received LONSURF in combination with bevacizumab had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (60% vs 46%) and Grade 3 or 4 thrombocytopenia (5% vs 4%).

Renal Impairment: No adjustment to the starting dosage of LONSURF is recommended in patients with mild or moderate renal impairment (CLcr of 30 to 89 mL/min). Reduce the starting dose of LONSURF for patients with severe renal impairment (CLcr of 15 to 29 mL/min) to a recommended dosage of 20 mg/m².

Hepatic Impairment: Do not initiate LONSURF in patients with baseline moderate or severe (total bilirubin > 1.5 times ULN and any AST) hepatic impairment. Patients with severe hepatic impairment (total bilirubin > 3 times ULN and any AST) were not studied. No adjustment to the starting dosage of LONSURF is recommended for patients with mild hepatic impairment.

ADVERSE REACTIONS

Serious adverse reactions occurred in 25% of patients. The most frequent serious adverse reactions (≥2%) were intestinal obstruction (2.8%), and COVID-19 (2%). Fatal adverse reactions occurred in 1.2% of patients who received LONSURF in combination with bevacizumab, including rectal fistula (0.4%), bowel perforation (0.4%) and atrial fibrillation (0.4%).

The most common adverse reactions or laboratory abnormalities (≥10% in incidence) in patients treated with single agent LONSURF at a rate that exceeds the rate in patients receiving placebo in mCRC: anemia (77% vs 33%), neutropenia (67% vs 0.8%), asthenia/fatigue (52% vs 35%), nausea (48% vs 24%), thrombocytopenia (42% vs 8%), decreased appetite (39% vs 29%), diarrhea (32% vs 12%), vomiting (28% vs 14%), abdominal pain (21% vs 19%), and pyrexia (19% vs 14%). In metastatic gastric cancer or gastroesophageal junction (GEJ): neutropenia (66% vs 4%), anemia (63% vs 38%), nausea (37% vs 32%), thrombocytopenia (34% vs 9%), decreased appetite (34% vs 31%), vomiting (25% vs 20%), infections (23% vs 16%) and diarrhea (23% vs 14%).

Pulmonary emboli occurred more frequently in LONSURF-treated patients compared to placebo: in mCRC (2% vs 0%) and in metastatic gastric cancer and GEJ (3% vs 2%).

Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.

The most common adverse reactions or laboratory abnormalities (≥20% in incidence) in patients treated with LONSURF in combination with bevacizumab vs LONSURF alone were neutropenia (80% vs 68%), anemia (68% vs 73%), thrombocytopenia (54% vs 29%), fatigue (45% vs 37%), nausea (37% vs 27%), increased aspartate aminotransferase (34% vs 28%), increased alanine aminotransferase (33% vs 23%), increased alkaline phosphate (31% vs 36%), decreased sodium (25% vs 20%), diarrhea (21% vs 19%), abdominal pain (20% vs 18%), and decreased appetite (20% vs 15%).

Please see full Prescribing Information.