Comments on: UK Watchdog NICE Turns Down Four New Kidney Cancer Drugs http://www.reportbuyer.com/blog/uk-watchdog-nice-turns-down-four-new-kidney-cancer-drugs/ Sharing intelligence Fri, 09 Jan 2009 11:18:00 +0000 http://wordpress.org/?v=2.2 By: natalia http://www.reportbuyer.com/blog/uk-watchdog-nice-turns-down-four-new-kidney-cancer-drugs/#comment-234261 natalia Mon, 22 Sep 2008 10:56:20 +0000 http://www.reportbuyer.com/blog/uk-watchdog-nice-turns-down-four-new-kidney-cancer-drugs/#comment-234261 Data from a Phase II study of GlaxoSmithKline's Tykerb in head and neck cancer point to the potential for it to achieve expansion beyond the breast cancer market. Phase III development of the drug in the adjuvant head and neck cancer setting could prove to be more successful than an initial launch in the advanced/metastatic setting, where competition from Erbitux is likely to restrict sales. In the randomized Phase II study, 107 patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN) received either Tykerb (lapatinib; GlaxoSmithKline) or a placebo before treatment with standard platinum-based chemotherapy and radiotherapy. The results showed a statistically significant reduction in tumor cell proliferation in the Tykerb arm of the study (-8% vs -2.7% in the placebo arm, p=0.039). In 88 patients who underwent radiological analysis, the overall response rate was higher in the Tykerb arm than in the placebo arm (86% vs 63%) and the complete response rate was also higher in the Tykerb arm (28% vs 7%). However, GlaxoSmithKline did not state whether the difference in response rates reached statistical significance. Tykerb is an orally available small molecule that inhibits two key receptors associated with tumor growth: EGFR (ErbB1) and HER2 (ErbB2). A number of tumors show overexpression of at least one of these receptors, including SCCHN, where it is associated with a poor prognosis. Tykerb is approved in the US and EU in combination with Xeloda (capecitabine; Roche) for the treatment of advanced or metastatic HER2-positive breast cancer which has progressed following treatment with Herceptin (trastuzumab; Genentech/Roche). Erbitux (cetuximab; ImClone/Bristol-Myers Squibb/Merck Serono), a monoclonal antibody which also targets EGFR, is the only targeted therapy available for head and neck cancer, and is approved in the US and EU for advanced/metastatic SCCHN. Erbitux’s first-to-market advantage and its established status as standard-of-care could restrict the uptake of other targeted therapies commercialized for advanced/metastatic SCCHN. It appears likely that GlaxoSmithKline does not initially intend for Tykerb to compete directly with Erbitux in locally advanced/metastatic SCCHN. Instead, it has launched a Phase III study evaluating Tykerb plus concurrent chemotherapy/radiotherapy in the adjuvant setting in patients who have undergone surgical resection (the MAINTYNANCE trial). If Tykerb is successful in this Phase III trial, it could achieve considerable market penetration in this area, given the lack of competition from other approved targeted therapies. However, while the reported Phase II results for Tykerb in locally advanced SCCHN suggest promising activity in this tumor type, it is far from certain whether this will translate into meaningful efficacy in the adjuvant setting. Data from a Phase II study of GlaxoSmithKline’s Tykerb in head and neck cancer point to the potential for it to achieve expansion beyond the breast cancer market. Phase III development of the drug in the adjuvant head and neck cancer setting could prove to be more successful than an initial launch in the advanced/metastatic setting, where competition from Erbitux is likely to restrict sales.
In the randomized Phase II study, 107 patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN) received either Tykerb (lapatinib; GlaxoSmithKline) or a placebo before treatment with standard platinum-based chemotherapy and radiotherapy. The results showed a statistically significant reduction in tumor cell proliferation in the Tykerb arm of the study (-8% vs -2.7% in the placebo arm, p=0.039). In 88 patients who underwent radiological analysis, the overall response rate was higher in the Tykerb arm than in the placebo arm (86% vs 63%) and the complete response rate was also higher in the Tykerb arm (28% vs 7%). However, GlaxoSmithKline did not state whether the difference in response rates reached statistical significance.

Tykerb is an orally available small molecule that inhibits two key receptors associated with tumor growth: EGFR (ErbB1) and HER2 (ErbB2). A number of tumors show overexpression of at least one of these receptors, including SCCHN, where it is associated with a poor prognosis. Tykerb is approved in the US and EU in combination with Xeloda (capecitabine; Roche) for the treatment of advanced or metastatic HER2-positive breast cancer which has progressed following treatment with Herceptin (trastuzumab; Genentech/Roche).

Erbitux (cetuximab; ImClone/Bristol-Myers Squibb/Merck Serono), a monoclonal antibody which also targets EGFR, is the only targeted therapy available for head and neck cancer, and is approved in the US and EU for advanced/metastatic SCCHN. Erbitux’s first-to-market advantage and its established status as standard-of-care could restrict the uptake of other targeted therapies commercialized for advanced/metastatic SCCHN.

It appears likely that GlaxoSmithKline does not initially intend for Tykerb to compete directly with Erbitux in locally advanced/metastatic SCCHN. Instead, it has launched a Phase III study evaluating Tykerb plus concurrent chemotherapy/radiotherapy in the adjuvant setting in patients who have undergone surgical resection (the MAINTYNANCE trial). If Tykerb is successful in this Phase III trial, it could achieve considerable market penetration in this area, given the lack of competition from other approved targeted therapies. However, while the reported Phase II results for Tykerb in locally advanced SCCHN suggest promising activity in this tumor type, it is far from certain whether this will translate into meaningful efficacy in the adjuvant setting.

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