Breast cancer: A step forward for Nektar, a half-step back for Glaxo

SAN FRANCISCO & LONDON—So, it's a goodnews/bad news thing with breast cancer drug development, with some forwardmomentum on the U.S. side of the Atlantic with Nektar Therapeutics and a littleloss in momentum on the U.K. side with GlaxoSmithKline PLC (GSK).

Going for the good news first, Nektar hasannounced positive results from its Phase II clinical study of NKTR-102 inpatients with metastatic breast cancer. NKTR-102 is a novel topoisomerase Iinhibitor designed using Nektar's proprietary polymer conjugate technology, andis being developed in multiple tumor settings. The drug is said to have a "uniquepharmacokinetic profile that provides a continuous exposure to active drug withreduced peak concentrations"  and alsohas been evaluated in a Phase II studies for the treatment ofplatinum-refractory/resistant ovarian cancer—in addition to being tested as a single agent in a Phase II clinicaltrial in patients with second-line colorectal cancer and a Phase I clinicaltrial evaluating NKTR-102 in combination with 5-FU therapy.

In this metastatic breast cancer study, NKTR-102exhibited "a very high response rate and excellent clinical benefit rate inpatients with metastatic breast cancer, and importantly, this anti-tumoractivity is maintained in each of the poor prognosis subsets within the study,"according to NKTR-102 study investigator Dr. Agustin Garcia, associateprofessor of clinical medicine at USC Norris Comprehensive Center. "The datafrom the Phase 2 study also shows highly promising PFS of 5.3 months and OS of13.1 months in the every three week dose schedule, which was also verywell-tolerated. As a novel topoisomerase I inhibitor in breast cancer, NKTR-102holds great therapeutic potential and allows us to address the challenge ofresistance in this setting. The investigators look forward to the initiation ofthe Phase 3 BEACON study of NKTR-102 in patients with metastatic breast cancer."

NKTR-102 reportedly exhibited minimal alopecia,neuropathy and neutropenia, which are among the adverse events associated with manyexisting breast cancer therapies. Side effects were generally manageable, accordingto Nektar, with the most common Grade 3 toxicity being diarrhea (in 17 percentto 23 percent of patients), typically occurring after three months of therapyfor both dosing schedules being studied.

The company also announced the design of theplanned Phase III clinical trial of NKTR-102 in metastatic breast cancerpatients in its BEACON study (BrEAst Cancer Outcomes with NKTR-102), withreported plans to enroll approximately 840 metastatic breast cancer patientswho have had prior treatment with anthracycline, taxane and capecitabine ineither the adjuvant or metastatic setting. The global BEACON study, which willinclude over 130 investigator sites, is expected to begin in December 2011.

GSK, on the other hand, suffered a small setbackin its Phase III clinical trial of breast cancer drug Tykerb (lapatinib).Although the study itself will continue, it has been scaled back so that the companywill no longer administer the drug alone, following the decision of anindependent committee that doing so was likely to produce worse results than usingRoche's Herceptin (trastuzumab) alone.

The other three arms of the trial, designed to examineTykerb's performance in combination with Herceptin, will continue as planned,GSK says. 

"Patients assigned to the lapatinib-alone arm ofthe trial will discontinue lapatinib and discuss treatment options with theirstudy physician," GSK said in the clinical trial update.

GSK's Phase III ALTTO trial (Adjuvant Lapatiniband/or Trastuzumab Treatment Optimization) aims to find out whether acombination of the drugs works better than the Roche drug alone.

GSK is studying Tykerb as an adjuvant therapy forpatients with HER2-positive primary breast cancer. While Tykerb is approved inmore than 100 countries, including the United States, as a cancer treatment, itis not yet approved as an adjuvant therapy anywhere in the world. The U.S. Foodand Drug Administration approved Tykerb in 2007 to be used in combination withanother Roche product, the chemotherapy drug Xeloda, to treat patients withadvanced or metastatic breast cancer.

While Tykerb's sales have been growing, bringingGSK more than $360 million revenue in 2010—and $154 million last year in theU.S. alone, it is far from blockbuster levels, so GSK has been looking toexpand the potential range of uses for Tykerb.