23LBA BEAM: A randomized phase II study evaluating the activity of BEvacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated Advanced Melanoma

O’Day, Steven; Kim, K.B.; Sosman, Jeff; Peterson, Alexander C; Feng, Shisen; Minor, David R.; Fruehauf, John P.; Linette, Gerald P.; Markovic, S. N.; Carson, W. E.

doi:10.1016/s1359-6349(09)72058-0

Cited by 33 publications

(25 citation statements)

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“…Although some in vitro studies have favored dasatinib (20), sunitinib may have an advantage over other KIT inhibitors given its antiangiogenic activity through the inhibition of VEGFR1, VEGFR2, VEGFR3, and platelet-derived growth factor receptor (PDGFR). Several phase II studies have shown the activity of other angiogenesis inhibitors in the treatment of unselected patients with metastatic melanoma (21,22). Although the data in GISTs suggest that sunitinib is more effective against patients with exon 9 than in exon 11 mutations, we observed responses in 2 of 3 evaluable patients with exon 11 mutations.…”

Section: Discussioncontrasting

confidence: 62%

Sunitinib Therapy for Melanoma Patients with KIT Mutations

Minor

Kashani‐Sabet

Garrido

et al. 2012

Clinical Cancer Research

177

103

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Purpose: Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib.Experimental Design: Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117). Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST).Results: Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ. Of 12 patients treated with sunitinib, 10 were evaluable. Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1-and 7-month duration). In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response. In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT. Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P < 0.0001).Conclusions: Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma.

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Section: Discussioncontrasting

confidence: 62%

Sunitinib Therapy for Melanoma Patients with KIT Mutations

Minor

Kashani‐Sabet

Garrido

et al. 2012

Clinical Cancer Research

177

103

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“…A phase II study of carboplatin/paclitaxel plus bevacizumab showed promising activity in 53 patients treated (24). The trial, known as the BEAM trial, tested carboplatin/paclitaxel/bevacizumab (N=143) randomized versus carboplatin/paclitaxel (N=71)(25). The combination showed non-significant improvements in all endpoints (response: 25.5% vs. 16.4%, p=0.16; PFS: 5.6 vs. 4.2 months, p=0.14; OS: 12.3 vs. 9.2 months, p=0.06).…”

Section: Discussionmentioning

confidence: 99%

Aflibercept (VEGF Trap) in Inoperable Stage III or Stage IV Melanoma of Cutaneous or Uveal Origin

Tarhini

Frankel

Margolin

et al. 2011

Clinical Cancer Research

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Purpose Aflibercept is a soluble decoy VEGF receptor and angiogenesis inhibitor with potent preclinical antitumor activity in melanoma. We conducted a multicenter phase II study in patients with inoperable stage III or IV melanoma and no prior chemotherapy. Experimental Design A 2-stage design was adopted to evaluate 4-month PFS rate (PFSR) and response rate. Aflibercept was given at 4 mg/kg IV every 2 weeks. Response was assessed every 8 weeks. First stage accrual of 21 patients was specified, and with an adequate 4-month PFSR accrual continued to a total of 41. Results Forty-one patients of age 23–84 (median 57) were enrolled. Thirty-nine had AJCC stage IV (5M1a, 7M1b, 27M1c) and 2 had inoperable stage IIIC (N3). ECOG PS was 0 (27 patients), or 1 (14 patients). Ten patients had primary uveal melanoma, 28 cutaneous and 3 unknown primaries. A median of 7 cycles were initiated (range 1–56). Grade 3/4 toxicities included hypertension in 9 patients (22%) and proteinuria in 6 (15%). Among 40 patients evaluable for efficacy (those who initiated aflibercept), 3 (7.5%) had a confirmed PR, and twenty had PFS of ≥4 months. The predicted one year survival rate derived from the Korn meta-analysis model is 36% (N=39), while we observed a corresponding 56.4% survival at one year (95% CI 43%–74%), p<0.005. Median OS in this trial is 16.3 months, (95% CI 9.2 mos–not reached). We observed a significant association between severity of hypertension following aflibercept and survival improvement. Conclusions Aflibercept demonstrated promising activity in patients with metastatic melanoma of cutaneous or uveal origin. Further evaluation of aflibercept as a single agent and in combination is warranted.

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“…To date, no systemic chemotherapy has been shown to be effective in patients with noncutaneous melanoma. The combination of paclitaxel/ carboplatin (PC) has been shown to be effective in some malignancies, including metastatic melanoma [13][14][15][16][17]. For example, results of a phase II trial and a retrospective review showed that PC was associated with an objective response rate (ORR) of B20-25% [14,15].…”

Section: Introductionmentioning

confidence: 99%

Effect of paclitaxel/carboplatin salvage chemotherapy in noncutaneous versus cutaneous metastatic melanoma

et al. 2013

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Little is known about the efficacy of salvage chemotherapy for patients with metastatic, noncutaneous melanoma after the failure of dacarbazine-based chemotherapy. Because of the high incidence of noncutaneous melanoma in Korea, we assessed the outcomes of paclitaxel/carboplatin (PC) salvage chemotherapy in patients with noncutaneous metastatic melanoma. We retrospectively analyzed patients with metastatic melanoma who received intravenous paclitaxel (175 mg/m) plus intravenous carboplatin (area under the curve 5) on day 1 of a 21-day cycle as salvage chemotherapy at Samsung Medical Center (SMC) between February 2009 and February 2012. The overall response rate, overall survival, and progression-free survival were evaluated. Thirty-two patients with a median age of 54 years (range 24-72 years) received PC as salvage chemotherapy. All patients had been pretreated with a median of three systemic chemotherapies. Of the 32 patients, 10 (31.3%) had cutaneous melanoma, eight (25%) had acral melanoma, 10 (31.3%) had mucosal melanoma, and two (6.3%) had ocular melanoma. In response to treatment, seven of the 32 patients (21.9%) achieved partial response and 11 (34.4%) had stable disease. The median progression-free survival was 2.53 months for all patients, 4.3 months for patients with controlled disease (partial response and stable disease), and 1.37 months for patients with progressive disease (P=0.0001). The median overall survival was 5.2 months. No significant difference was noted between patients with noncutaneous and cutaneous metastatic melanoma (P=0.75). PC salvage chemotherapy may be a reasonable therapeutic option for heavily pretreated metastatic melanoma patients. Salvage therapy with this combination had definite clinically meaningful benefits in patients with metastatic melanoma, including those with noncutaneous melanoma.

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23LBA BEAM: A randomized phase II study evaluating the activity of BEvacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated Advanced Melanoma

Cited by 33 publications

References 0 publications

Sunitinib Therapy for Melanoma Patients with KIT Mutations

Sunitinib Therapy for Melanoma Patients with KIT Mutations

Aflibercept (VEGF Trap) in Inoperable Stage III or Stage IV Melanoma of Cutaneous or Uveal Origin

Effect of paclitaxel/carboplatin salvage chemotherapy in noncutaneous versus cutaneous metastatic melanoma

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