Final analysis: A randomized, blinded, placebo (P)-controlled phase III study of adjuvant postoperative lapatinib (L) with concurrent chemotherapy and radiation therapy (CH-RT) in high-risk patients with squamous cell carcinoma of the head and neck (SCCHN).

Abstract

6005 Background: Epidermal growth factor receptor (EGFR) and ErbB2 are overexpressed in up to 90% and 40% of SCCHN, respectively. L, a tyrosine kinase inhibitor (TKI) of both EGFR and ErbB2, demonstrates tumor responses in SCCHN. Methods: Patients with resected stage II-IVA SCCHN, with a surgical margin ≤5mm and/or extracapsular extension were randomized to CT-RT with either P or L. RT was 66Gy (2Gy per day, 5 days per week).100 mg/m2of cisplatin was administered on days 1, 22 and 43 of RT. P or L 1500 mg/day was given for up to one week prior to CT-RT, during CT-RT and for up to 12 months as monotherapy maintenance. Patients were stratified by nodal status, primary tumor location, geographical region and ErbB1 expression. The study had 80% power to detect a 10% absolute difference in disease free survival (DFS) rate (55% to 65%). Results: 688 patients were in the ITT population, 346 L and 342 P. Treatment arms were well balanced for prognostic factors. Median total doses of cisplatin (266.5 and 280 mg/m2, L and P respectively) and median doses and duration of RT were similar in both arms. At the time of unblinding, recurrence/death from any cause was seen in 35% in L and 32% in P by independent review committee (IRC): Median DFS (95% CI) L: 53.6 mo (45.8, Not Reached [NR]); P: NR (54.6, NR), HR (95% CI) = 1.10 (0.85, 1.43) 2-sided p value = 0.45. Investigator results confirmed the IRC assessment: HR 1.03 (0.81, 1.30), p=0.82. No significant differences were observed in DFS for any of the pre-specified subgroups, including HPV. Death occurred in 30% L and 32% P; HR (95% CI) = 0.96 (0.73, 1.25). At least one adverse event was seen in 99% L and 98% P (SAEs 48% L/40% P, fatal AEs 7% L/5% P). AEs seen more in L were those expected with a TKI: diarrhea 42% vs 12%, rash 49% vs 30%, vomiting 46% vs 35%. Decrease in left ventricular ejection fraction SAEs were noted in 10 (3%) subjects L vs 3 (<1%) P. Conclusions: In patients with resected SCCHN at high risk for recurrence, L, when added to standard therapy RT/CDDP, does not extend DFS. DFS in both treatment arms exceeded adjuvant CT-RT compared with historical randomized data. Clinical trial information: NCT00424255.