Cancer Research Highlights

Drug Combination More Effective than Single Drug for Advanced Melanoma

The combination of two targeted drugs—dabrafenib and trametinib—may delay the progression of advanced melanoma longer than dabrafenib alone, a new study suggests. These results, presented September 29 at the 2012 European Society for Medical Oncology Congress (ESMO) and published concurrently in the New England Journal of Medicine, add to a growing body of evidence that combinations of targeted drugs for melanoma are more effective and less toxic than a single targeted drug.

Dabrafenib and trametinib target different parts of a cell signaling pathway altered in melanoma by a mutation called BRAF V600. Single drugs that block BRAF activity shrink melanoma, but the tumors inevitably develop resistance. Researchers hoped that adding a second drug with a different target would slow the development of resistance and disease progression.

In the first part of the randomized phase II trial, which enrolled 85 patients, the researchers determined the combination’s safety and the doses to be used in the trial. The researchers then randomly assigned 162 patients to one of three treatment groups: dabrafenib alone, dabrafenib plus a low dose of trametinib, or dabrafenib plus a higher dose of trametinib. Patients whose disease progressed with dabrafenib alone were allowed to add the higher dose of trametinib to their treatment.

Patients receiving the higher dose of trametinib plus dabrafenib had a median progression-free survival of 9.4 months compared with 5.8 months for patients receiving dabrafenib alone. After 1 year of follow-up, 41 percent of patients receiving the higher-dose of trametinib plus dabrafenib had no disease progression, compared with 9 percent of those who received dabrafenib alone.

Overall, 79 percent of patients in the higher-dose combination group were alive after 1 year, explained Dr. Georgina Long of the Melanoma Institute Australia, one of the study’s authors, at an ESMO press conference. “We have never, ever seen a 12-month survival of that level in metastatic melanoma to date,” she said.

Side effects differed among the treatment groups, and patients in all arms of the trial frequently required temporary or permanent dose reductions. More patients receiving dabrafenib alone (19 percent) developed a secondary squamous-cell skin cancer than patients receiving the higher-dose combination (7 percent), though this difference was not statistically significant. Most patients in the higher-dose combination group (71 percent) experienced a fever compared with a minority of those receiving dabrafenib alone (26 percent).

The trial was funded by GlaxoSmithKline, the drugs’ manufacturer. Two company-sponsored phase III trials of the drug combination are currently under way (here and here).

Further reading:

• “Targeted Drug Shows Potential in Advanced Solid Tumors and Brain Metastases”
• “Researchers Uncover New Mechanism of Resistance to Melanoma Drug”
• “New Therapies Offer Much-Needed Options for Patients with Melanoma”
• “Melanoma Drugs Have Unintended Effects in Some Tumors”
• "Possible Causes of Resistance to Melanoma Drug Reported”

Health Care Costs a Major Barrier for Young Adult Cancer Survivors

Many young adult cancer survivors do not seek routine medical care because of cost concerns, according to a new study. Even after accounting for health insurance status, survivors of adolescent and young adult (AYA) cancers were much more likely to forgo care in the prior year because of cost concerns, researchers reported September 24 in Cancer.

The results point to potentially serious consequences for AYA cancer survivors, the authors explained. “Medical care in the years following cancer therapy is particularly important to screen survivors for late effects, such as secondary cancers, infertility, and cardiac conditions,” they wrote.

Although the greater availability of health insurance for young adults as a result of the Affordable Care Act will help, they continued, the study indicates “that improvements in post-treatment health care access must be prioritized for this population.”

The study focused on long-term survivors diagnosed and treated between the ages of 15 and 34.

To conduct the study, the researchers used 2009 data from the Centers for Disease Control and Prevention’s Behavioral Risk Factor Surveillance System, a nationwide, state-based system of health surveys conducted each month by telephone. The study included responses from 979 AYA cancer survivors between the ages of 20 and 39 who were at least 5 years past their cancer diagnosis (case subjects) and approximately 67,000 people in the same age range who did not have a history of cancer (control subjects).

Overall, 34 percent of survivors reported forgoing routine care because of cost, compared with 20 percent of control subjects. The groups most affected by cost concerns were survivors between the ages of 20 and 29 and female survivors, Dr. Anne Kirchhoff of the Huntsman Cancer Institute in Utah and her colleagues reported.

AYA survivors also reported being in poor or fair health more often (27 percent versus 9 percent for control subjects) and experiencing frequent mental or physical distress. Forty percent of survivors had not had a routine medical visit in the past year, and 22 percent did not have a personal medical care provider.

Further reading: 

• “Many Survivors of Adolescent and Young Adult Cancers Have Chronic Health Problems, Unhealthy Behaviors”
• “Special Issue: Adolescent and Young Adult Cancers”

Many Women whose Tumors Disappear after Chemotherapy Have Mastectomies

Many women with breast cancer whose tumors disappear after presurgical chemotherapy have a mastectomy instead of breast-conserving surgery, according to a re-analysis of data from the NeoALTTO trial. The results were presented September 30 at the 2012 European Society for Medical Oncology Congress (ESMO).

In the phase III trial, investigators randomly assigned women with HER2-positive breast cancer to receive trastuzumab, lapatinib, or both drugs for a total of 18 weeks prior to surgery. (Both drugs target the HER2 receptor.) After the first 6 weeks, paclitaxel chemotherapy was added to the anti-HER2 treatments.

In 160 of 429 women, the tumors disappeared (a pathologic complete response). But whether a woman had a pathologic complete response did not influence the type of surgery she had later. Although women receiving all three drugs were up to twice as likely to have their tumors disappear as women who received only a single anti-HER2 drug plus paclitaxel, they were no more likely to have breast-conserving surgery than a mastectomy.

Instead, the ultimate choice of surgery type was more strongly influenced by the characteristics of the tumor before chemotherapy, including the initial tumor size and whether the tumor expressed the estrogen receptor, as well as the type of surgery originally planned and whether the cancer was multifocal or multicentric.

One of the main goals of presurgical (neoadjuvant) chemotherapy is to “downstage” larger tumors to allow less-aggressive surgery. Therefore, “there is a need for a clear consensus on the role of breast-conserving surgery, especially in patients who respond to neoadjuvant therapy,” said lead investigator Dr. Carmen Criscitiello, of the European Institute of Oncology in Milan, Italy, at an ESMO press conference.

“This will ultimately translate…into improved breast-conservation rates, [and] could spare more women from receiving radical treatment like mastectomy,” she concluded.