Abraxane and Avastin for melanoma – pro

Handsome doctor talking with his patient for the annual check-up

Metastatic melanoma responds poorly to chemotherapy with the main drugs being temozolomide or dacarbazine after failure of immunotherapy with ipilimumab or vaccination. However, Abraxane has been reported to have single agent activity. This response rate is higher than observed previously with paclitaxel or docetaxel suggesting that this formulation of paclitaxel may be more active than the conventional form. Among the 37 chemotherapy-naive patients, researchers reported a 22% partial response rate and 49% disease control rate. Median PFS was 4.5 months and median OS was 9.6 months.

In 2009, Hersh and colleagues initiated the phase 3 CA033 trial.

The international, multicenter, randomized study compared nab-paclitaxel with dacarbazine (DTIC) in chemotherapy-naive patients with metastatic malignant melanoma.

The investigation included 529 patients with stage IV disease, a performance status of 0 to 1, and no brain metastasis.

The researchers assigned 264 patients to receive nab-paclitaxel 150 mg/m2 IV on days 1, 8 and 15 every 4 weeks. The other 265 patients received dacarbazine 1,000 mg/m2 once every 3 weeks.

Patient characteristics — including age (media, 63 years; range, 21 to 87 years), sex, region of the world, ECOG performance status and metastatic stage — were similar between the two arms.

PFS served as the primary endpoint and OS served as the secondary endpoint. Other endpoints included overall response rate, disease control rate and safety/tolerability.

The results, presented in November at the Society for Melanoma Research Congress, showed that patients assigned to nab-paclitaxel demonstrated superior median PFS (4.8 months vs. 2.5 months; HR=0.792; 95.1% CI, 0.631-0.992).

At the time of planned interim analysis, nab-paclitaxel also was associated with longer OS (12.8 months vs. 10.7 months; HR=0.831; 99.9% CI, 0.578-0.1.196).

As a single agent, Avastin has been found to produce responses and disease stabilization in patients with metastatic melanoma. A study from Spain has also found the combination of Taxol and Avastin to have clinical benefit in over half of the patients with metastatic melanoma(Gonzalez Cao et al).  NCCN lists it as an alternative, but not specifically for second line.

Abraxane and Avastin is under study in a phase II trial at Northern California Melanoma Center, an open-label, single arm multicenter Phase II study to evaluate the safety and efficacy of the combination of Abraxane and Avastin as first-line therapy for patients with unresectable metastatic malignant melanoma. Early experience suggests that nab-paclitaxel and bevacizumab is an effective and well-tolerated regimen as first-line therapy in patients with metastatic melanoma(Boasberg et al).

P. Boasberg, S. Cruickshank, O. Hamid, S. O’Day, R. Weber, L. Spitler;  Nab-paclitaxel and bevacizumab as first-line therapy in patients with unresectable stage III and IV melanoma. J Clin Oncol 27:15s, 2009 (suppl; abstr 9061^)

Perez DG, Suman VJ, Fitch TR, et al. Phase 2 trial of carboplatin, weekly paclitaxel, and biweekly bevacizumab in patients with unresectable stage IV melanoma. Cancer. 2009;115:119-127.

Jaissle GB, Ulmer A, Henke-Fahle S, et al. Suppression of melanoma-associated neoangiogenesis by bevacizumb. Archives of Dermatology. 2008;144:525-527.

Varker KA, Biber JE, Kefauver C, et al. A randomized phase 2 trial of bevacizumab with J Clin Oncol 29: 2011 (suppl; abstr 8532)

L. A. Kottschade, V. Suman, D. G. Perez, R. R. McWilliams, J. S. Kaur, T. Amatruda, F. J. Geoffroy, H. M. Gross, P. A. Cohen, A. J. Jaslowski, M. L. Kosel, S. Markovic; Mayo Clinic, Rochester, MN; Minnesota Hematology/Oncology, PA, St. Louis Park, MN; Hubert H. Humphrey Cancer Center, Robbinsdale, MN; Illinois Cancer Care, Peoria, IL; NSABP; Dayton CCOP, Dayton, OH; Mayo Clinic, Scottsdale, AZ; Green Bay Oncology, Green Bay, WI, A randomized phase II trial of temozolomide (TMZ) and bevacizumab (BEV) or nab-paclitaxel (nab-P)/carboplatin (CBDCA) and bevacizumab (BEV) in patients with unresectable stage IV metastatic melanoma: A North Central Cancer Treatment Group Study (N0775). J Clin Oncol 29: 2011 (suppl; abstr 8532)

Gonzalez-Cao M, Viteri S, Diaz-Lagares A, et al. Preliminary results of the combination of bevacizumab and weekly paclitaxel in advanced melanoma. Oncology. 2008;74:12-16.

Hersh E, O’Day S, Gonzalez R, et al.Multicenter phase II study of ABI-007 (Abraxane) in previously treated and chemotherapy nave patients with metastatic malignant melanoma (MMM). Proceedings from the 23rd annual Chemotherapy Foundation Symposium. 2005. New York, NY. Abstract #27.

Walker L, Schalch H, King DM, et al. Phase II trial of weekly paclitaxel in patients with advanced melanoma. Melanoma Research . 2005;15:453-459.

Bedikian AY, Plager C, Papadopoulos N, et al. Phase II evaluation of paclitaxel by short intravenous infusion in metastatic melanoma. Melanoma Research . 2004;63-66.Hersh EM. Taxanes in melanoma: Are they the new chemotherapy standard? Presented at: HemOnc Today Melanoma and Cutaneous Malignancies meeting; March 22-23, 2013; New York.

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