Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Abstract

Funding: GSK (subsequently Novartis) funded this study. There are no NIH grants related to this work.COI: RBC has served as a consultant to GSK. CJL has served as a consultant to Novartis. The remaining authors report no COIs directly related to this work. Précis:Patients with first line recurrent/metastatic head and neck cancer were treated with the all-oral regimen capecitabine and lapatinib. mPFS was 4.2 months and mOS was 10.7 months. Keywords: head and neck neoplasms, capecitabine, lapatinib Page 2 of 72 CancerThis article is protected by copyright. All rights reserved. Accepted Article Abstract:Background: Combination of cisplatin, 5FU and cetuximab is a standard treatment for recurrent/metastatic head and neck cancer with a high rate of toxicity.Identifying less toxic, equally effective regimens is imperative. We therefore investigated first-line treatment with an all-oral regimen of capecitabine and lapatinib.Materials and Methods: Patients were required to have incurable head and neck cancer of any primary site other than nasopharynx, PS0-2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine 1000mg/m 2 BID and lapatinib 1250mg daily. Capecitabine was administered for 14 of 21 days for 4 cycles. Lapatinib was administered daily until progression. The primary outcome was overall survival (OS).Results: 44 subjects were accrued between 11/13/2009 and 4/29/2014. Patients with PS0 were 38.6% of the sample, PS1 52.3%, and PS2 9.1%. 81.8% were male and the median age was 62 years. Prior attempts at curative treatment with chemotherapy had been utilized in 68.2% of patients (platinum used in 55.8%).There was no grade 5 toxicity. The most common adverse events were diarrhea (18.2% G3) and rash (13.6% G3). The primary objective was met; OS was 10.7 months (90% CI 8.7 to 12.9). Overall response rate was 25% (90% CI: 15%-38%).PFS was 4.2 months (90% CI 3.6 to 5.1). Results were not substantially different when subdivided by p16 status. Only two patients were positive for HER2 by IHC.Conclusions: The study met its primary objective of survival comparable to the EXTREME regimen and toxicity of this all-oral regimen was tolerable. Page 3 of 72 CancerThis article is protected by copyright. All rights reserved. Accepted Article Introduction:Recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains incurable in the vast majority of cases. Cisplatin-containing regimens have been the standard treatment platform for more than 2 decades. The most recent advance was the addition of cetuximab to a cis-or carboplatin-containing regimen, which increased overall survival from 7.4 to 10.1 months compared to chemotherapy alone [1]. The EXTREME regimen represented the first significant breakthrough in the treatment of R/M HNSCC, but it came at a price. Adverse events in both arms of the EXTREME trial were significant; 76% of patients receiving 5FU and platinum experienced grade 3-4 adverse events, and 82% of patients receiving cisplatin, 5FU, and cetuximab experienced grade 3...

Phase 2 trial of neoadjuvant chemotherapy and transoral endoscopic surgery with risk‐adapted adjuvant therapy for squamous cell carcinoma of the head and neck

“…Possible explanations for this include the activity of lapatinib, the activity of the cytotoxic backbone, and the risk level of the population accrued. Regarding lapatinib, we note that multiple clinical studies have been published between study inception and the current article that cast doubt on its activity . Used as a single agent in metastatic/recurrent disease, the response rate was 0%.…”

“…Regarding lapatinib, we note that multiple clinical studies have been published between study inception and the current article that cast doubt on its activity. [14][15][16] Used as a single agent in metastatic/recurrent disease, the response rate was 0%. When combined with capecitabine in metastatic/recurrent disease, the outcome appeared to be similar to that expected with capecitabine alone.…”

Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells

“…The cytotoxicity of baicalin and baicalein was similar. Cisplatin was used as a positive control, a well-known anticancer agent (32,33). The IC 50 values of baicalin were 54.3 μ M for HSC-2 cells, 60.6 μ M for HSC-3 cells, and 69.0 μ M for HaCaT cells.…”

Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma (Review)

“…The preliminary trials of it in the treatment of HNSCC have demonstrated its activity in the p-16 negative tumors in combination with chemoradiotherapy (43). A combination of lapatinib and capecitabine can be well-tolerated and active in the metastatic and recurrent forms of HNSCC (44). The ability of lapatinib to inhibit the two receptors can allow a break of the mechanisms underlying resistance to therapy aimed at EGFR antibodies through signal transduction (44).…”

“…A combination of lapatinib and capecitabine can be well-tolerated and active in the metastatic and recurrent forms of HNSCC (44). The ability of lapatinib to inhibit the two receptors can allow a break of the mechanisms underlying resistance to therapy aimed at EGFR antibodies through signal transduction (44). Afatinib is an irreversible TKI that blocks the transmission of signals from all homo-and heterodimers formed by receptors of the ErbB family.…”