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The combination of axitinib followed by paclitaxel/carboplatin yields extended survival in advanced BRAF wild-type melanoma: results of a clinical/correlative prospective phase II clinical trial.

Algazi AP, Cha E, Ortiz-Urda SM, McCalmont T, Bastian BC, Hwang J, Pampaloni MH, Behr S, Chong K, Cortez B, Quiroz A, Coakley F, Liu S, Daud AI - Br. J. Cancer (2015)

Bottom Line: The treatment was well tolerated.Five BRAF(V600E/K) patients had significantly worse PFS than patients without these mutations.Axitinib followed by carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type metastatic melanoma. 3'-Deoxy-3'-(18)F-fluorothymidine-PET scans showed increased proliferation during axitinib withdrawal.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, 1600 Divisadero St MTZ-A741, San Francisco, CA 94143-1770, USA.

ABSTRACT

Background: Simultaneous chemotherapy with vascular endothelial growth factor (VEGF) inhibition has not shown additional benefit over chemotherapy alone in advanced melanoma. We tested administration of the potent VEGF inhibitor axitinib followed by paclitaxel/carboplatin to determine whether enhanced tumour proliferation during axitinib withdrawal leads to sustained chemosensitivity.

Methods: We conducted a prospective phase II trial in metastatic melanoma patients with ECOG performance status 0-1 and normal organ function. Axitinib 5 mg PO b.i.d. was taken on days 1-14 of each 21-day treatment cycle, and carboplatin (AUC=5) with paclitaxel (175 mg m(-2)) was administered on day 1 starting with cycle 2. 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT)-PET scans were performed in five patients to assess tumour proliferation on days 1, 14, 17, and 20 of cycle 1. Molecular profiling for BRAF was performed for all patients with cutaneous, acral, or mucosal melanoma.

Results: The treatment was well tolerated. The most common grade 3 AEs were hypertension, neutropenia, and anaemia. Grade 4 non-haematologic AEs were not observed. Four of five patients completing (18)F-FLT-PET scans showed increases (23-92%) in SUV values during the axitinib holiday. Of 36 evaluable patients, there were 8 confirmed PRs by Response Evaluation Criteria in Solid Tumors. Overall, 20 patients had SD and 8 had PD as the best response. The median PFS was 8.7 months and the median overall survival was 14.0 months. Five BRAF(V600E/K) patients had significantly worse PFS than patients without these mutations.

Conclusions: Axitinib followed by carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type metastatic melanoma. 3'-Deoxy-3'-(18)F-fluorothymidine-PET scans showed increased proliferation during axitinib withdrawal.

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Sum of individual target lesion maximum 18F-FLT SUV values in five patients undergoing serial 18F-FLT-PET scans during the first treatment cycle. The treatment holiday began on day 14 and ended after day 21. Abbreviations: PR=partial response, SD=stable disease, PD=progression of disease as best response.
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fig4: Sum of individual target lesion maximum 18F-FLT SUV values in five patients undergoing serial 18F-FLT-PET scans during the first treatment cycle. The treatment holiday began on day 14 and ended after day 21. Abbreviations: PR=partial response, SD=stable disease, PD=progression of disease as best response.

Mentions: Five patients completed both pre- and post-treatment 18F-FLT-PET scans (Figure 4). One patient had minimal 18F-FLT uptake at baseline. In two patients, decreases in the sum of maximum 18F-FLT uptake values were noted (25.2% and 48.3%) on day 14 of axitinib therapy followed by increases of 43% and 28.2% from their nadirs, respectively, during the treatment holiday. Another patient had an increase of 23% on day 14 and an increase of 57% from baseline after the 7-day treatment holiday. A fifth patient did not undergo a follow-up 18F-FLT-PET study on day 14, but had a 95% increase in 18F-FLT uptake from baseline by the end of the treatment holiday.


The combination of axitinib followed by paclitaxel/carboplatin yields extended survival in advanced BRAF wild-type melanoma: results of a clinical/correlative prospective phase II clinical trial.

Algazi AP, Cha E, Ortiz-Urda SM, McCalmont T, Bastian BC, Hwang J, Pampaloni MH, Behr S, Chong K, Cortez B, Quiroz A, Coakley F, Liu S, Daud AI - Br. J. Cancer (2015)

Sum of individual target lesion maximum 18F-FLT SUV values in five patients undergoing serial 18F-FLT-PET scans during the first treatment cycle. The treatment holiday began on day 14 and ended after day 21. Abbreviations: PR=partial response, SD=stable disease, PD=progression of disease as best response.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402449&req=5

fig4: Sum of individual target lesion maximum 18F-FLT SUV values in five patients undergoing serial 18F-FLT-PET scans during the first treatment cycle. The treatment holiday began on day 14 and ended after day 21. Abbreviations: PR=partial response, SD=stable disease, PD=progression of disease as best response.
Mentions: Five patients completed both pre- and post-treatment 18F-FLT-PET scans (Figure 4). One patient had minimal 18F-FLT uptake at baseline. In two patients, decreases in the sum of maximum 18F-FLT uptake values were noted (25.2% and 48.3%) on day 14 of axitinib therapy followed by increases of 43% and 28.2% from their nadirs, respectively, during the treatment holiday. Another patient had an increase of 23% on day 14 and an increase of 57% from baseline after the 7-day treatment holiday. A fifth patient did not undergo a follow-up 18F-FLT-PET study on day 14, but had a 95% increase in 18F-FLT uptake from baseline by the end of the treatment holiday.

Bottom Line: The treatment was well tolerated.Five BRAF(V600E/K) patients had significantly worse PFS than patients without these mutations.Axitinib followed by carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type metastatic melanoma. 3'-Deoxy-3'-(18)F-fluorothymidine-PET scans showed increased proliferation during axitinib withdrawal.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Hematology/Oncology, University of California, 1600 Divisadero St MTZ-A741, San Francisco, CA 94143-1770, USA.

ABSTRACT

Background: Simultaneous chemotherapy with vascular endothelial growth factor (VEGF) inhibition has not shown additional benefit over chemotherapy alone in advanced melanoma. We tested administration of the potent VEGF inhibitor axitinib followed by paclitaxel/carboplatin to determine whether enhanced tumour proliferation during axitinib withdrawal leads to sustained chemosensitivity.

Methods: We conducted a prospective phase II trial in metastatic melanoma patients with ECOG performance status 0-1 and normal organ function. Axitinib 5 mg PO b.i.d. was taken on days 1-14 of each 21-day treatment cycle, and carboplatin (AUC=5) with paclitaxel (175 mg m(-2)) was administered on day 1 starting with cycle 2. 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT)-PET scans were performed in five patients to assess tumour proliferation on days 1, 14, 17, and 20 of cycle 1. Molecular profiling for BRAF was performed for all patients with cutaneous, acral, or mucosal melanoma.

Results: The treatment was well tolerated. The most common grade 3 AEs were hypertension, neutropenia, and anaemia. Grade 4 non-haematologic AEs were not observed. Four of five patients completing (18)F-FLT-PET scans showed increases (23-92%) in SUV values during the axitinib holiday. Of 36 evaluable patients, there were 8 confirmed PRs by Response Evaluation Criteria in Solid Tumors. Overall, 20 patients had SD and 8 had PD as the best response. The median PFS was 8.7 months and the median overall survival was 14.0 months. Five BRAF(V600E/K) patients had significantly worse PFS than patients without these mutations.

Conclusions: Axitinib followed by carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type metastatic melanoma. 3'-Deoxy-3'-(18)F-fluorothymidine-PET scans showed increased proliferation during axitinib withdrawal.

Show MeSH
Related in: MedlinePlus