PC3016: Nivolumab and Lenvatinib Immunochemotherapy in 20 Children and Young Adults with Unresectable or Metastatic Fibrolamellar Carcinoma

Background: Fibrolamellar Carcinoma (FLC) is a rare deadly form of primary liver cancer affecting healthy young adults, often presenting at an advanced stage, with up to 80% relapse, and no proven effective systemic therapies. Unresectable FLC patients are considered incurable and have short life expectancy. Because of some rare successes as monotherapy we tried the combination of nivolumab (NIV) and lenvatanib (LEN) in metastatic, relapsed, or unresectable FLC patients who were ineligible for clinical trials.

Methods: We reviewed the records of all FLC patients seen at our institution who received NIV-LEN over the last 5 years.

Results: Twenty patients (6M/15F), median age 20 (6-55), all stage IV, received a total of 295 cycles of nivolumab 3mg/kg IV q2 weeks and lenvatanib 8mg po daily, (11 neoadjuvant, 8 adjuvant, 1 both), with a mean follow up of 15 months (2-31) since initiation of NIV-LEN and 47 months (5-186) from diagnosis. The progression free survival /overall survival at 6, 12, and 18 months are: 83%/94%, 68%/94%, and 60%/68%. The median number of cycles/months was 17 (3-47) / 10 (2-30) respectively. The median number of relapses, prior systemic therapies, and surgeries were 4 (0-7), 3 (0-11), and 5 (0-19) respectively. The best response by RECIST 1.1 of the 12 neoadjuvant patients was CR(3), PR(3), SD(5), and PD(1), for an objective response rate (PR + CR) of 50% and disease control rate (CR + PR + SD) of 92% at median follow up of 16 months. Estimated mean volume change was a mean of - 44% (+24% to -100%). Seven of 9 who had adjuvant NIVO-LEN remain in CR (78%) at 10 month mean follow-up. Thirteen of 20 are continuing on NIV-LEN. Four of 11 unresectable patients became surgical candidates all getting R0 resections. Eight patients stopped therapy: PD (3), infection (3) or patient's wishes (2). The time to progression (TTP) was longer than the previous TTP in 18 patients and was the longest TTP in 6 of 20. The most common toxicities were hypertension and fatigue in 25% and 20% respectively, grade 1 or 2. The longest treated patient (47 cycles, 2.3 years) is a now 22 year old who after 5 relapses, 6 surgeries and 7 previous systemic therapies, most recently with > 100 lung nodules, resolved on therapy and is in sustained remission for 17 months (Figure 1).

Conclusion: Our retrospective experience with the novel combination of NIV-LEN offer the first description of this combination for FLC and a potential option for patients who are not surgical candidates or with multiple relapses. NIV-LEN was well tolerated with the majority of patients reporting improved quality of life. Prospective trials are needed. We hope this report can inform future directions in treating this deadly disease.