Phase II trial with axitinib in recurrent and/or metastatic salivary gland cancers of the upper aerodigestive tract

Abstract

Background Patients with prognosis recurrent/metastatic (R/M) salivary gland carcinomas (SGCs) are poor. Activity of axitinib was demonstrated in adenoid cystic carcinoma (ACC). We tested axitinib in a larger cohort of R/M SGCs including non‐ACC. Methods Axitinib was administered at 10 mg daily (dose escalation allowed) until progression or unacceptable toxicity. Null hypothesis would be rejected if more than 3 of 26 responses were observed. Results Twenty‐six patients (50% were male; 6 ACC, 20 non‐ACC) were treated. Response rate was 8% (2 partial responses), 13 stable disease (>6 months in 7 patients) and 11 disease progression. Median progression‐free survival and overall survival were 5.5 and 26.2 months, respectively. All patients had at least one adverse event: stomatitis (69%), fatigue (58%) and hypertension (54%) were the most frequent. Conclusions This trial did not meet its primary endpoint hence axitinib should not be considered for further investigations in SGCs. Safety profile was in line with the scientific literature.

Centralised RECIST Assessment and Clinical Outcomes with Lenvatinib Monotherapy in Recurrent and Metastatic Adenoid Cystic Carcinoma

“…An ORR of 46.2% was reported which compares favourably with the ORR of 12-15% observed for lenvatinib as well as those reported in other TKIs trialled in R/M ACC, including axitinib [14,15], sorafenib [10][11][12][13], and sunitinib [32]. The median PFS was 19.7 months, and the median OS was not reached, both comparing favourably with lenvatinib and other TKIs [8][9][10][11][12][13][14][15][16][17][18][19]. Interestingly, patients who received a higher intensity of apatanib treatment had significantly longer PFS than those receiving a lower intensity (p = 0.024, HR 0.033, 95% CI 0.002-0.639).…”

“…The study required radiological evidence of disease progression before enrollment to evaluate the contribution of apatinib to disease stabilisation. An ORR of 46.2% was reported which compares favourably with the ORR of 12-15% observed for lenvatinib as well as those reported in other TKIs trialled in R/M ACC, including axitinib [14,15], sorafenib [10][11][12][13], and sunitinib [32]. The median PFS was 19.7 months, and the median OS was not reached, both comparing favourably with lenvatinib and other TKIs [8][9][10][11][12][13][14][15][16][17][18][19].…”

“…Wholegenome sequencing of patient ACC samples has identified mutations in genes involved in the FGF/IGF/PI3K pathway [9]. However multi-kinase inhibitors (MKI) targeting this pathway, such as sorafenib [10][11][12][13] and axitinib [14,15], have shown minimal efficacy in treating patients with ACC. Other targeted therapies, such as imatinib [16], gefitinib [17], dasatinib [18], and dovitinib [19] have shown no significant activity assessed by RECIST (response valuation criteria in solid tumours) criteria.…”

Management of Salivary Gland Malignancy: ASCO Guideline

“…Other targeted therapies including axitinib, 38 tipifarnib, 259 gefitinib, 27 and lapatinib 357 have demonstrated clinical benefit rather than significant objective responses in small phase II studies, and these remain investigational. Recommendation 6.6.…”

Targeted Therapy, Chemotherapy, Immunotherapy and Novel Treatment Options for Different Subtypes of Salivary Gland Cancer

“…For VEGFR, it was found that there was an association with recurrence and metastases [47]. Medication tested in phase II trials included dovitinib (FGFR, VEGFR, PDGFR, c-Kit) [48,49], sunitinib (VEGFR, c-Kit, PDGFR) [50], regorafenib (VEGRF, FGFR, PDGFR) [51], nintedanib (VEGFR, FGFR, PDGFR) [52], lenvatinib (VEGFR, FGFR, PDGFR) [53,54], axitinib (VEGFR, PDGFR, c-Kit) [55,56], and sorafenib (VEGFR, PDGFR, c-Kit) [62,76]. For sunitinib, regorafenib, and nintedanib, no overall response rates could be seen.…”