LONSURF + bevacizumab extended survival and prolonged PFS in 3L mCRC
LONSURF + bevacizumab extended survival and prolonged PFS in 3L mCRC
In SUNLIGHT, LONSURF + bevacizumab delivered ~11 months median OS (10.8 vs 7.5 months) and more than double the median PFS (5.6 vs 2.4 months) vs LONSURF alone1,2
SUNLIGHT study design1,2
Study population
(N=492)
(n=246)
LONSURF 35 mg/m2* orally,
twice daily Days 1-5 and 8-12
every 28 days
Bevacizumab 5 mg/kg by IV,
Days 1 and 15
(n=246)
LONSURF alone
35 mg/m2* orally, twice
daily Days 1-5 and 8-12 every 28 days
Treatment until disease progression, unacceptable toxic effects, or withdrawn consent
Follow-up every 8 weeks for radiologic progression and/or survival status
Primary endpoint
- OS
Secondary endpoints
- PFS
- ORR
- DCR
- Time to worsening
to ECOG PS ≥2 - Safety
Key inclusion criteria
- ECOG performance status (PS) of 0-1
- Disease progression or intolerance
- Histologically confirmed unresectable adenocarcinoma of the colon or rectum
- No more than 2 previous chemotherapy regimens†
- Previous treatment must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti–vascular endothelial growth factor (VEGF) monoclonal antibody (not necessarily bevacizumab), or an anti–epidermal growth factor receptor (EGFR) monoclonal antibody (for patients with RAS wild-type disease)
- Known RAS status
Stratification
Randomization was stratified according to:
- Geographic region (North America, the European Union, or the rest of the world)
- Time since diagnosis of first metastasis (<18 months or ≥18 months)
- RAS status (wild type or mutated)
*Starting dose.2
†The treatment could have included neoadjuvant or adjuvant chemotherapy if disease had recurred during treatment or within 6 months after the last administration of neoadjuvant or adjuvant therapy.2
Key baseline characteristics2
| Characteristic | LONSURF + bevacizumab (n=246) | LONSURF (n=246) | |
|---|---|---|---|
| Age | Median, years (range) | 62 (20-84) | 64 (24-90) |
| <65 years, n (%) | 146 (59) | 129 (52) | |
| ≥65 years, n (%) | 100 (41) | 117 (48) | |
| Sex, n (%) | Male | 122 (50) | 134 (55) |
| Race or ethnic group, n (%) | White | 215 (87) | 220 (89) |
| Black | 4 (2) | 3 (1) | |
| Asian | 0 | 1 (<1) | |
| American Indian or Alaska Native | 1 (<1) | 0 | |
| Other | 8 (3) | 5 (2) | |
| Unknown | 18 (7) | 17 (7) | |
| Region, n (%) | European Union | 158 (64) | 157 (64) |
| North America | 8 (3) | 8 (3) | |
| Rest of the world | 80 (33) | 81 (33) | |
| Location of primary tumor, n (%) | Right side | 62 (25) | 77 (31) |
| Left side | 184 (75) | 169 (69) | |
| Time from diagnosis of first metastasis to randomization,a n (%) | <18 months | 104 (42) | 105 (43) |
| ≥18 months | 142 (58) | 141 (57) | |
| RAS status,a n (%) | Mutant | 171 (70) | 170 (69) |
| Wild-type | 75 (31) | 76 (31) | |
| Prior treatment with anti-VEGF monoclonal antibody, n (%) | Yes | 178 (72) | 176 (72) |
| ECOG PS, n (%) | 0 | 119 (48) | 106 (43) |
| 1 | 127 (52) | 139 (57) | |
| 2 | 0 | 1 (<1)b | |
aData were determined from the interactive web-based response system used for randomization.2
bThe patient had an ECOG PS of 1 at randomization but was assessed as having a score of 2 on Day 1 of the first treatment cycle.2
months
months
At the time of the analysis,13% of the patients treated with LONSURF + bevacizumab and 1.6% treated with LONSURF alone were still receiving treatment.
PRIMARY ENDPOINT
~11 months mOS in 3L mCRC
Overall Survival (OS) (N=492)1,2
Hazard ratio (HR)=0.61 (95% CI: 0.49-0.77), P<0.001
| OS comparison at key timepoints2,3 | 6 months | 12 months | 18 months |
|---|---|---|---|
| LONSURF + bevacizumab | 77% | 43% | 28% |
| LONSURF | 61% | 30% | 15% |
OS across major subgroups of patients2
Results were consistent across all clinically relevant subgroups regardless of age, sex, location of primary disease, number of metastatic sites, RAS mutation status, and prior bevacizumab treatment.2
KEY SECONDARY ENDPOINT
Median PFS more than doubled vs an active comparator
Progression-free Survival (PFS) (N=492)1,2
HR=0.44 (95% CI: 0.36-0.54), P<0.001
| PFS comparison at key timepoints2 | 6 months | 12 months | 18 months |
|---|---|---|---|
| LONSURF + bevacizumab | 43% | 16% | Not estimable |
| LONSURF | 16% | 1% | Not estimable |
At just under 16 months, PFS was 0% in the LONSURF arm vs 7.9% in the LONSURF + bevacizumab arm.
PFS across major subgroups of patients2
Results were consistent across all clinically relevant subgroups regardless of age, sex, location of primary disease, number of metastatic sites, RAS mutation status, and prior bevacizumab treatment.2
ADDITIONAL SECONDARY ENDPOINTS
More than three-quarters of patients achieved disease control4
Disease control rate (DCR)4
LONSURF +
bevacizumab
(n=222)
LONSURF
alone
(n=215)
Objective response rate (ORR)2
LONSURF +
bevacizumab
LONSURF
alone
DCR=objective response + stable disease; ORR=complete response + partial response.
on to receive subsequent therapy following the trial5
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
Recommended
The National Comprehensive Cancer Network® (NCCN®) recommends trifluridine and tipiracil (LONSURF) +/- bevacizumab as NCCN Category 2A recommended options for a potential third-line or subsequent treatment in mCRC patients. The trifluridine and tipiracil (LONSURF) + bevacizumab combination is preferred over trifluridine and tipiracil (LONSURF) alone.6,7
Category 2A=based upon lower-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
Potential treatment algorithm for 3L use (KRAS/NRAS wild type)6
Initial therapy
FOLFOX +
cetuximab
2L therapy
FOLFIRI +
bevacizumab
Subsequent therapies*
Trifluridine and tipiracil
(LONSURF) +/- bevacizumab
or
Fruquintinib, regorafenib,
clinical trials, or best supportive care
Potential treatment algorithm for use as a subsequent therapy (KRAS/NRAS mutant)6
Initial therapy
FOLFIRINOX +
bevacizumab
Subsequent therapies*
Trifluridine and tipiracil
(LONSURF) +/- bevacizumab
or
Fruquintinib, regorafenib,
clinical trials, or best supportive care
NCCN Guidelines® do not recommend a single-agent fluoropyrimidine after progression on a fluoropyrimidine-containing regimen. Bevacizumab is the preferred anti-angiogenic agent and can be continued into the second line of therapy and beyond.6,7
*Fruquintinib or regorafenib or trifluridine and tipiracil +/- bevacizumab are treatment options for patients who have progressed through all available regimens.