STATEMENT OF NEED

The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the art care for those with or at risk for cancer.

TARGET AUDIENCE

Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

OVERALL EDUCATIONAL OBJECTIVES

Upon completion, participants should be able to:

• Describe new preventive options and treatments for cancer patients
• Identify options for individualizing the treatment for cancer patients
• Review new evidence to facilitate survivorship and supportive care for cancer patients

ACCREDITATION STATEMENT

Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hours. RNs outside California must verify with their licensing agency for approval of this course.

DISCLOSURES

The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.

METHOD OF PARTICIPATION

• Read the articles in this section in its entirety.
• Go to www.dannemiller.com/onn-nov-dec-2012.
• Complete and submit the CE posttest and activity evaluation.
• Print your Certificate of Credit.

This activity is provided free of charge to participants.

Breast Cancer

Lapatinib Plus Trastuzumab Bests Solo Lapatinib in Metastatic Breast Cancer

By Jill Stein

Investigators have documented a significant 4.5-month median overall survival advantage with lapatinib combined with trastuzumab versus lapatinib monotherapy in women with heavily pretreated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC).

The findings are from an update of the phase III EGF104900 study (J Clin Oncol. 2012;30(21):2585- 2592), which had found in an earlier analysis that combination therapy significantly improved progression-free survival (PFS), the primary endpoint (HR = 0.73; 93% CI, 0.57-0.93; P = .008) versus lapatinib alone.

Overall, the data bolster the hypothesis that combining anti-HER2 agents “may optimize their use,” Kimberly L. Blackwell, MD, professor of Medicine and assistant professor of Radiation Oncology at Duke University Medical Center in Durham, North Carolina, and associates wrote.

The updated analysis is based on data from January 2009 and includes all 291 patients with HER2-positive MBC who were randomized to lapatinib in tandem with trastuzumab or to lapatinib alone after their disease had progressed during prior trastuzumab-based therapy. The earlier PFS results were drawn from data available in June 2007.

The updated analysis found that lapatanib plus trastuzumab continued to demonstrate superiority to lapatinib monotherapy in investigator-assessed PFS (HR = 0.74; 95% CI, 0.58-0.94; P = .011). In addition, the median OS was 14 months for combination therapy and 9.5 months for lapatinib alone (HR = 0.74; 95% CI, 0.57-0.97; P = .026).

The data also showed a 10% improvement in absolute overall survival (OS) rate at 6 months and a 15% improvement at 12 months in the combination group versus the monotherapy group.

Overall, 94% of patients who received combination therapy and 90% of patients who received monotherapy experienced adverse events.

Blackwell et al pointed out that their findings corroborate preclinical data indicating that the lapatinib plus trastuzumab combination has synergistic antiproliferative activity.

They also emphasized that “clinically relevant” OS improvement occurred even though more than half of women who were initially randomized to lapatinib monotherapy switched to combination therapy upon disease progression.

Finally, they noted that the median 4.5-month survival advantage is on par with improvements that have been reported when trastuzumab is added to chemotherapy as frontline treatment for HER2-positive MBC.

“Although the optimal setting for combining anti-HER2 agents is unknown, this strategy seems beneficial and may allow patients to omit chemotherapy for a period of time,” they said.

Nurse Perspective on Lapatinib Plus Trastuzumab

Peg Farrar, MS, RNInstructor, Carrington CollegeReno, NV

Women with metastatic breast cancer are facing many difficult choices these days. There are many new regimens which may be helpful, and new research often compares a known monotherapy regimen with a newer combination of drugs that may have a better outcome.

This study also points out one of the serious issues that these women must deal with—adverse events. The review did not explicate what the adverse events were, or how serious they were, but it is difficult to experience many of them over and over. As one patient told me, “This will be the third time I have lost all my hair.”

However, the improvement in overall survival and progression-free survival are significant, and should be considered. Patients with metastatic disease must make hard decisions, based on their personal situation and concerns, so the nurse needs to make certain that all choices are presented with all of the risks and benefits, and support the patient’s decision, whatever it may be.

Head and Neck Cancer

Meningioma Risk May Be Tied to Dental X-Rays

By Jill Stein

New data suggest that dental x-rays obtained frequently at a young age may boost the risk of intracranial meningioma.

“Although dental x-rays are an important tool in well-selected patients, efforts to moderate exposure to IR [ionizing radiation] to the head is likely to be of benefit to patients and healthcare providers alike,” Elizabeth B. Claus, MD, professor and director of Medical Research at Yale University School of Public Health, New Haven, Connecticut, and attending neurosurgeon at Brigham and Women’s Hospital in Boston, and her coauthors wrote (Cancer. 2012;118(18):4530-4537).

For their study, the investigators compared dental and therapeutic radiation histories in 1433 patients who had intracranial meningioma diagnosed when they were between 20 and 79 years of age with histories from 1350 healthy controls matched for age, sex, and state of residence.

While meningioma is the most common brain tumor diagnosed in adults in the US and may lead to neurologic complications with a decreased quality of life, there is limited information on risk factors for this lesion, Claus et al pointed out.

Exposure to IR has consistently been found to be associated with a higher incidence of meningiomas, with relative risks ranging from 6- to 10-fold, they added.

Notably, dental x-rays are the most common artificial source of exposure to IR for individuals residing in the US.

Also, unlike many risk factors, exposure to dental x-rays is modifiable.

The analysis showed that over a lifetime, cases were more than twice as likely as controls (odds ratio [OR], 2.0; 95% CI, 1.4-2.9) to report having ever had bitewing films.

Regardless of the age at which the x-ray films were taken, individuals who reported receiving bitewing films annually or with greater frequency had an increased risk of meningioma for ages <10 years (OR, 1.4; 95% CI, 1.0-1.8), ages 10 to 19 years (OR, 1.6; 95% CI, 1.2-2.0), ages 20 to 39 years (OR, 1.9; 95% CI, 1.4- 2.6), and ages ≥40 years (OR, 1.5; 95% CI, 1.1-2.0).

A significantly increased risk of meningioma was also associated with panorex films, in which an examination is taken outside of the mouth and shows all of the teeth on a single film.

Claus et al noted that their findings were bolstered by the study’s population-based design, large sample size, and “the relatively consistent magnitude and direction of risk estimates.”

On the other hand, the potential for underreporting or overreporting of dental x-rays by the study participants represented a study limitation. The reason is that dental care, even in a single patient, is usually obtained from multiple dentists who are not part of a health maintenance organization or hospital-based setting, which makes it difficult for researchers to confirm dental reports “in a timely or cost-efficient manner.”

Low-Dose Radioiodine Ablation Is Effective Treatment for Thyroid Cancer

By Jill Stein

Low-dose radioiodine ablation with thyrotropin alfa is as effective as highdose radioiodine ablation in patients with differentiated thyroid cancer and is safer, researchers reported (N Engl J Med. 2012;366(18):1674-1685).

The results also showed that the efficacy of lowdose radioiodine ablation is maintained when thyrotropin alfa was used instead of thyroid hormone withdrawal.

Ujjal Mallick, MD, consultant clinical oncologist at the Northern Centre for Cancer Treatment in Newcastle upon Tyne, United Kingdom, and colleagues randomized 438 patients to one of four treatment groups: low-dose (1.1 GBq) or high-dose (3.7 GBq) radioiodine, each combined with thyrotropin alfa or thyroid hormone withdrawal.

Thyroid cancer is the most common endocrine cancer, and more than 48,000 new cases are reported annually in the United States, the authors noted. The incidence of thyroid cancer is increasing worldwide and more than doubled in the United States from 1973 through 2006.

There are multiple advantages to using a lower dose of radioiodine, including shorter time in hospital isolation and fewer side effects, including a second primary cancer due to exposure to radioactive substances, they added. Ultimately, financial costs also are reduced.

Study participants had tumor stage T1 to T3 with the possibility of lymph node involvement but no distant metastasis.

The primary endpoint was the success rate for ablation, which was defined as both a negative scan on whole-body iodine-131 scanning (<0.1% uptake on the basis of the region-of-interest method drawn over the thyroid bed) and a thyroglobulin level of less than 2.0 ng/mL at 6 to 9 months.

Results showed that ablation was successful in 85.0% of patients randomized to low-dose radioiodine versus 88.9% of patients assigned to high-dose radioiodine.

Ablation success rates were 87.1% in the thyrotropin alfa group and 86.7% in the group undergoing thyroid hormone withdrawal.

Similar results were documented for low-dose radioiodine plus thyrotropin alfa (84.3%) versus highdose radioiodine plus thyroid hormone withdrawal (87.6%) or high-dose radioiodine plus thyrotropin alfa (90.2%).

The study also found that ablation rates were similar for low- and high-dose radioiodine ablation with either thyrotropin alfa or thyroid hormone withdrawal in subgroups of patients with stage T3 tumors and lymph node involvement.

Overall, 36.3% of patients in the high-dose group were hospitalized for at least 3 days versus 13.0% of patients in the low-dose group (P < .001). Also, 33% of patients in the high-dose group had adverse events versus 21% of patents in the low-risk group (P = .007) and 23% of patients in the thyrotropin alfa group versus 30% of patients in the group undergoing thyroid hormone withdrawal (P = .11).

“Our study answers two central questions involving radioiodine ablation of thyroid remnants after surgery for differentiated thyroid cancer; namely, that the efficacy of low-dose radioiodine is similar to that of high-dose radioiodine, and that the efficacy of low-dose radioiodine ablation is not compromised by the use of thyrotropin alfa instead of thyroid hormone withdrawal,” Mallick and colleagues wrote. “Previous small studies had conflicting results on both counts.”

They emphasized that their study focused on ablation success at 6 to 9 months and did not provide information on future recurrences.

Supportive Care

Adjunctive Ketamine Does Not Relieve Cancer Pain

By Jill Stein

Subcutaneous ketamine administered in conjunction with opioids and conventional adjuvant therapy does not lessen chronic uncontrolled cancer pain, according to the results of a phase III study (J Clin Oncol. 2012;30 (29)3611-3617).

Worse yet, the regimen produces a significant spike in toxicity.

Janet Hardy, MD, professor of Palliative Care at Mater Adult Hospital in South Brisbane, Australia, and colleagues elsewhere randomized patients to ketamine or placebo delivered subcutaneously over 3 to 5 days.

All patients had refractory chronic pain due to cancer or its treatment, with a Brief Pain Inventory average pain score ≥3 in spite of ongoing treatment with opioids and analgesics at prespecified dosage levels.

Pain management remains a significant problem in cancer care, even when patients have ready access to a variety of opioids and adjuvant therapies, the researchers pointed out. Although the dissociative agent ketamine is frequently used off-label with opioids for the management of pain secondary to cancer or its treatment, data on the use of ketamine for chronic cancer pain have been “extrapolated” largely from case series and uncontrolled studies in noncancer settings.

The primary outcome measure in the present study was a positive response, defined as a clinically relevant improvement in pain at the end of the 5-day study period.

Overall, 25 (27%) of 92 patients who received a placebo had a response versus 29 (31%) of 93 patients who received the intervention, with no difference (P = .55) between the proportion of positive outcomes in each group.

Pain type (nociceptive vs neuropathic) was not a statistically significant predictor of response.

The investigators also found nearly twice the incidence of adverse events determined to be worse than at baseline in the ketamine arm than the placebo arm at the end of day 1 (incidence rate ratio, 1.95; 95% CI, 1.46-2.61; P < .001) and throughout the study.

Ketamine-treated patients were also more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00-1.18; P = .039).

Significantly more ketamine-treated patients dropped out of the study because of toxicity.

Hardy and colleagues said that they are confident that type II error did not contribute to the findings given “the consistency of the results across secondary outcomes and the fact that the study was adequately powered to detect our prespecified differences in responses.”

They also noted that whereas it may be tempting to consider the heterogeneous study sample as a possible limitation, the patient population is representative of those patients commonly referred to a palliative care service and who are given ketamine for pain.

Nurse Perspective on Adjunctive Ketamine

Kristin Barber, RN, MSN, APRNUtah Cancer SpecialistsSalt Lake City, UT

Just recently I realized, again, how fortunate we are in oncology to make our decisions based on evidence and randomized clinical trials. Not all specialties do this, and even more important, not all intuitive interventions actually positively impact cancer care.

This study confirms this finding. Ketamine, the analgesic often used for children for minor procedures was not found to be beneficial in conjunction with opioids and other analgesics for treating cancer-related pain. Those who may have been using this previously had evidence based only on case studies and nonrandomized trials. Also, ketamine showed more adverse events and toxicities than the placebo arm.

In our practice we commonly use a variety of opioids in various administration options. We also use many nonopioid medications like antidepressants, anticonvulsants, corticosteroids, and topical agents. Until we have more evidence, I would not use ketamine to treat cancer-related pain.

Prostate Cancer

Abiraterone Acetate Significantly Improves Survival in mCRPC Patients

By Ben Leach

A final analysis of a phase III COU-AA-301 trial comparing abiraterone acetate plus prednisone with a placebo in patients with metastatic castration-resistant prostate cancer (mCRPC) found that abiraterone significantly improved overall survival with positive responses seen in several subgroups of patients (Lancet Oncol. 2012;13(10):983-992).

Abiraterone acetate, which is marketed under the brand name Zytiga by Janssen Biotech, is designed to block all sources of production of testosterone, and therefore delay progression of the disease.

The study enrolled 1195 patients at 147 sites in 13 countries. These patients had been diagnosed with mCRPC and progressed after being treated with docetaxel, a standard of care for this group of patients. The study randomized patients to receive either abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily (n = 797) or a placebo plus prednisone 5 mg twice daily (n = 398). The primary endpoint of the study was overall survival (OS).

The final analysis found that after a median follow-up period of 20.2 months, the median OS in patients in the abiraterone arm of the study was 15.8 months compared with 11.2 months in the placebo arm.

Other endpoints also favored abiraterone. The median time to prostate-specific antigen (PSA) progression was 8.5 months in the abiraterone group compared with 6.6 months in the placebo arm.

Abiraterone was also favored in terms of median radiologic progression-free survival (PFS), with the abiraterone arm achieving a median PFS of 5.6 months compared with 3.6 months in the placebo arm. PSA response was also higher in the abiraterone arm, with 235 of 797 (29.5%) achieving a response compared with 22 of 398 (5.5%) patients in the placebo arm.

“Our work confirms that abiraterone acetate can be used as an effective and safe treatment for castration-resistant metastatic prostate cancer patients whose disease continues to progress after docetaxel treatment,” said lead author Karim Fizazi, MD, Institut Gustave Roussy in France, in a statement. “Furthermore, unlike current alternatives for this patient population, abiraterone plus prednisone therapy can be given orally in an outpatient setting, providing an additional benefit for both patients and clinicians.”

In a commentary that accompanied the study, Guru Sonpavde, MD, director of Urologic Medical Oncology at the University of Alabama, Birmingham, Comprehensive Cancer Center, praised the results, but he also stressed the need for further studies of the proper sequencing of abiraterone with other therapies, given that newer therapies such as sipuleucel-T and enzalutamide have also been recently approved to treat prostate cancer.

“[This trial] represents an important advance in the therapy of metastatic castration-resistant prostate cancer,” wrote Sonpavde. “[Further] clinical trials investigating novel drugs and combinations should be strongly encouraged since all available options are palliative in nature.”

Nurse Perspective on Abiraterone Acetate

Marieta Branis, APN, NP-CJohn Theurer Cancer CenterHackensack, NJ

According to the American Cancer Society (ACS), prostate cancer is the second leading cause of cancer death among men in the United States. Approximately 241,740 men will be diagnosed with prostate cancer in 2012 and 28,170 men will die of the disease (ACS, 2012). One in six men will be diagnosed with prostate cancer over a lifetime, and the average age of diagnosis is 67 (ACS, 2012). Various treatment modalities are available for patients diagnosed with prostate cancer, but up until recently, not too many options were available for those with metastatic castration-resistant prostate cancer (mCRPC) who had failed prior chemotherapy treatments.

The results of the phase III COU-AA-301 trial indicate that abiraterone acetate (Zytiga) in combination with prednisone, improves overall survival (OS), as well as progression-free survival, in patients with mCRPC who failed prior treatment with docetaxel. The study indicates an important improvement in patients’ OS of approximately 4 months, which is statistically significant for the treatment approach of this patient population.

Abiraterone works by blocking the androgen production at the testes, adrenal glands, and at the tumor site itself. In terms of side effects, abiraterone is well tolerated, which enhances the patient’s compliance with the therapy. Hypertension, hypokalemia, edema, and hepatotoxicity are the most frequently experienced side effects of abiraterone therapy, and these are usually clinically managed successfully in the outpatient setting.

From a nursing perspective, it is important to provide comprehensive patient education in order to minimize the severity of the adverse reactions. Instructing the patients about the importance of taking abiraterone on an empty stomach, with no food consumption for 2 hours prior to taking the dose, or at least 1 hour after taking the dose, is a significant aspect of enhancing the success of the therapy. Furthermore, rigorous blood pressure screening before initiation and during therapy, careful monitoring of serum potassium levels at baseline and periodically (at least every 4 weeks), and instructing the patient to immediately report signs and symptoms of fluid retention can help ensure safe delivery of the medication.

Lung Cancer

Dacomitinib Bests Erlotinib in Advanced Non—Small Cell Lung Cancer

By Jill Stein

Investigators reported improved progression- free survival (PFS) after treatment with the investigational agent dacomitinib compared with erlotinib in patients with non—small cell lung cancer (NSCLC) experiencing progression during chemotherapy (J Clin Oncol. 2012;30(27):3337-3344).

Erlotinib, which targets a single member of the HER family, inhibits signaling through competitive, reversible binding at the EGFR tyrosine kinase domain. The pan-HER inhibitor dacomitinib binds irreversibly to the adenosine triphosphate domain of all three kinase-active members of the HER family: EGFR, HER2, and HER4.

Suresh S. Ramalingam, MD, chief of the Thoracic Oncology Division at Emory Healthcare in Atlanta, Georgia, and coworkers randomized 188 patients to receive either 45 mg of oral dacomitinib or 150 mg of oral erlotinib once daily. In addition to having had no prior HER-directed therapy, patients enrolled in the phase II study had an ECOG performance status of 0 to 2 and had received one or two prior chemotherapy regimens. The primary endpoint of the study was PFS.

The study found that the median PFS was 2.86 months in the dacomitinib arm versus 1.91 months in the erlotinib group (hazard ratio [HR]=0.66; 95% CI, 0.47-0.91; two-sided P = .012).

An improvement in PFS was noted in most clinical and molecular subgroups. In patients with KRAS wild-type tumors, the median PFS was 3.71 months and 1.91 months for the dacomitinib and erlotinib treatment arms, respectively (HR = 0.55; 95% CI, 0.35- 0.85; two-sided P = .006). Patients with KRAS wild-type/ EGFR wild-type tumors receiving dacomitinib had a median PFS of 2.21 months compared with 1.84 months for patients treated with erlotinib (HR = 0.61; 95% CI, 0.37-0.99; two-sided P = .043).

Median overall survival was similar in the dacomitinib and erlotinib groups: 9.53 months in patients treated with dacomitinib and 7.44 months in patients who received erlotinib (HR = 0.80; 95% CI, 0.56-1.13; two-sided P = .205).

Treatment-related adverse events were more common with dacomitinib, primarily grade 1 and 2, and frequently involved skin and gastrointestinal events.

“The results documented here for dacomitinib suggest that irreversible pan-HER inhibition may offer a new treatment option for patients with advanced NSCLC, potentially representing an effective alternative to reversible inhibition of EGFR,” Ramalingam et al wrote.

The researchers suggested that the superior outcomes with dacomitinib might be due to its mechanism of action, “which potentially includes more complete inhibition of HER signaling by receptor homo- and heterodimerization through targeting of all three kinase-active HER receptors and permanent blockade of signaling by covalent receptor modification.”

No Survival Benefit Found When Adding Bevacizumab to Gemcitabine/Cisplatin in Malignant Mesothelioma

By Jill Stein

Adding the VEGF-inhibitor bevacizumab to gemcitabine/cisplatin does not significantly improve progression-free survival (PFS) or overall survival (OS) in patients with previously untreated, unresectable malignant mesothelioma (MM), according to the results of a phase II study (J Clin Oncol. 2012;30(20):2509-2515).

Hedy L. Kindler, MD, medical director of the Gastrointestinal Oncology Division at the University of Chicago, and colleagues elsewhere treated patients with 1250 mg/m2 of gemcitabine on days 1 and 8 every 21 days, 75 mg/m2 of cisplatin every 21 days, and 15 mg/kg of bevacizumab or placebo every 21 days for six cycles, and then bevacizumab or placebo every 21 days until progression. Random assignment was stratified by ECOG performance status (0 vs 1) and histology (epithelial vs sarcomatoid, mixed, or other subtypes).

Malignant mesothelioma is a rare malignancy, with about 2500 Americans diagnosed each year, Kindler et al wrote. Gemcitabine combined with cisplatin is active in mesothelioma, however, single-arm phase II studies have produced widely variable results. Small sample sizes, heterogeneity in patient prognostic factors, and diverse methods of response assessment are probable contributors to the divergent outcomes that have been reported, the researchers noted.

The addition of bevacizumab to chemotherapy has been shown to boost outcomes in breast, colon, lung, and kidney cancers. Because preclinical data suggested a major role for the VEGF pathway in MM biology, and several VEGF inhibitors have demonstrated modest single-agent activity in phase II studies of patients with MM, the study investigators decided that it was “plausible” that the addition of bevacizumab to systemic chemotherapy in patients with MM would yield similar favorable results. Since pemetrexed was not commercially available at the start of the trial, the popular gemcitabine/ cisplatin combination was selected for testing in combination with bevacizumab.

Study participants had an ECOG performance status of 0 to 1 and no thrombosis, bleeding, or major blood vessel invasion. Overall, 108 patients were evaluable. The primary endpoint was PFS.

The median PFS was 6.9 months for the bevacizumab arm and 6.0 months for the placebo arm (P = .88). The median OS was 15.6 and 14.7 months in the two treatment arms, respectively (P = .91). The partial response rate was similar in the bevacizumab and placebo arms (24.5% vs 21.8%; P = .74).

Baseline VEGF values obtained in 56 patients indicated that a higher pretreatment plasma VEGF concentration was associated with shorter PFS (P = .02) and OS (P = .0066), regardless of treatment assignment. The authors described this finding as “intriguing” but emphasized that it should be interpreted “cautiously” because of the relatively small sample sizes.

There were no statistically significant differences in the rates of grade 3 or greater toxicity between treatment groups.

Kindler et al noted that, to the best of their knowledge, this was the first randomized phase II study conducted in patients with MM.

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