Clinical Insights: October 2015
CE lesson worth 1.0 contact hours that are intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.
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.
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
Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.
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-oct-2015
- Complete and submit the CE posttest and activity evaluation.
- Print your Certificate of Credit.
This activity is provided free of charge to participants.
Hormones May Protect Ovaries, Preserve Fertility in Breast Cancer
Chemotherapy in young women can damage ovaries and result in premature menopause, but new research shows that the addition of hormonal treatment may preserve ovarian function and fertility in patients with breast cancer and may increase the chances of pregnancy after breast cancer treatment. The research, published in Annals of Oncology1 and presented at the 2015 European Cancer Congress held September 25-29 in Vienna, Austria (Abstract 1957), found that using luteinizing hormone-releasing hormone analogue (LHRHa) during chemotherapy is effective in preventing premature ovarian failure (POF) and may increase chances of pregnancy after breast cancer.
“We found that temporary suppression of ovarian function with LHRHa significantly reduces the risk of premature ovarian failure caused by chemotherapy. It also seems to be associated with a higher pregnancy rate in young breast cancer patients,” Matteo Lambertini, MD, medical oncologist at the IRCCS AOU San Martino-IST, Genoa, Italy, said in a statement.
The meta-analysis included 12 randomized trials and involved 1231 premenopausal patients with breast cancer receiving chemotherapy, with or without LHRHa.
An initial calculation found that rates of POF were reduced by 64% in patients who received LHRHa (Odds Ratio [OR] = 0.36; 95% CI, 0.23-0.57; P <.001). However, the studies used different definitions of POF, and results ranged widely.
The analysis was then restricted to eight studies that included specific data on whether a woman’s periods had restarted 1 year after chemotherapy. In the eight relevant trials, rates of POF with the addition of LHRHa were reduced by 45% (OR = 0.55; 95% CI, 0.41-0.73; P <.001), and there was close agreement in results from all studies.
The use of LHRHa was originally developed to preserve ovarian function rather than fertility, and only five of the studies reported pregnancies after breast cancer treatment. In these studies, overall there were 33 patients with pregnancies among those who received LHRHa alongside chemotherapy and 19 among those who did not. This was an 83% increase in the chance of becoming pregnant (OR = 1.83; 95% CI, 1.02-3.28, P = .041). Rates were similar across the five studies.
LHRHa treatment for breast cancers driven by hormones remains controversial, as previous work has implied that resumption of a woman’s periods after treatment could have a detrimental impact on long-term health.
“Major international guidelines from ASCO and ESMO consider the administration of LHRHa during chemotherapy an experimental strategy to preserve ovarian function and fertility. This is mainly because of the lack of data on long-term ovarian function and pregnancies. However, these guidelines were published before two of the larger studies became available, the POEMS-SWOG S0230 trial (N Engl J Med. 2015;372(23):2269—2270) and the updated results of the PROMISE-GIM6 study (J Clin Oncol. 2014;32(suppl 26): abstr 105),” Lambertini said.
Both studies examined disease-free survival (DFS). The POEMS-SWOG S0230 trial looked at women whose cancers were hormone receptor (HR)—negative, and found that women had improved DFS if they received LHRHa. The PROMISE-GIM6 study found that adding LHRHa made no difference to DFS, even within the subgroup of women with HR-positive breast cancer—the majority of the patients enrolled in the study.
“These data suggest that this strategy could be useful and safe not only in women with hormone receptor—negative breast cancer, but also in those with hormone receptor–positive tumors who account for two-thirds of new cases of breast cancer in young women,” Lambertini said.
The researchers concluded that current guidelines on fertility preservation for patients with breast cancer should consider using LHRHa during chemotherapy to increase the likelihood of patients’ resuming their periods and eventually becoming pregnant after treatment.
“Pharmacologic protection of the ovaries with LHRHa during chemotherapy is an attractive option to preserve ovarian function and fertility. Agents are widely available, do not require any invasive procedure, and cause no delay in the initiation of anticancer therapies,” Lambertini said.
“Moreover, it is possible to use this technique in combination with other fertility preservation options, including cryopreservation strategies, thereby increasing the chance of fertility preservation as well as ovarian function after cancer therapies.”
1. Lambertini M, Ceppi M, Poggio F, et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a systematic review and meta-analysis of randomized studies [published online ahead of print September 7, 2015] Ann Oncol.
Acupuncture Abates Hot Flashes in Breast Cancer Survivors
Hot flashes are severe, daily nuisances for many breast cancer survivors, but a few needle pricks from acupuncture may be enough to cool the unpleasant episodes, according to a new study published in the Journal of Clinical Oncology.
Researchers at the Perelman School of Medicine at the University of Pennsylvania found that electroacupuncture—in which needles deliver a weak electrical current—produced larger placebo and smaller nocebo effects than did gabapentin for treating hot flashes among breast cancer survivors.
Breast cancer survivors are restricted from taking FDA-approved treatment for hot flashes, such as hormone replacement therapies, because they include estrogen, but the Penn researchers concluded that electroacupuncture may be an effective management treatment.
“These latest results clearly show promise for managing hot flashes experienced by breast cancer survivors through the use of acupuncture, which in previous studies has also been proven to be an effective treatment for joint pain in this patient population,” lead author Jun J. Mao, MD, MSCE, associate professor of family medicine and community health, said in a statement.
This randomized controlled trial enrolled 120 breast cancer survivors who reported experiencing multiple hot flashes per day. Participants were randomly assigned to 1 of 4 groups, two involving active treatment and the other two placebo. The intervention was carried out over 8 weeks.
In the two treatment arms, participants received electroacupuncture twice per week for 2 weeks and then once weekly, or gabapentin (900 mg) daily. Survivors assigned to one of the placebo groups received either “sham” electroacupuncture, which involved no actual needle penetration or electrical current, or a daily placebo in place of the gabapentin.
Investigators used a hot flash composite score (HFCS) to measure hot flash frequency and severity. At the end of the 8 weeks, those in the electroacupuncture group showed the greatest reduction in HFCS (-7.4), followed by the sham acupuncture group, the gabapentin pill group, and the placebo pill group (-5.9 v -5.2 v -3.4, respectively).
The electroacupuncture group and the sham electroacupuncture group experienced 47.8% and 45% improvement in hot flashes, respectively. Improvement for the gabapentin group was 39.4% and 22.3% with placebo.
Both acupuncture groups reported fewer adverse events than the pill groups.
“We found that acupuncture elicited a greater placebo response than did pills, consistent with observations in studies of pain,” the authors wrote. “Although not completely understood, the enhanced placebo effect seen in acupuncture may be a combination of positive expectancy, patient—provider interaction, active patient engagement, relaxation, and light sensory stimulation by the sham needling.”
The groups were evaluated again 4 months after therapy ended to measure the durability of the treatment effects. Researchers found that survivors who received electroacupuncture had the best long-term effect (-8.5), followed by the sham acupuncture group (-6.1), placebo pill group (-4.6) and the gabapentin group (-2.8).
Electroacupuncture produced a 25% greater reduction in HFCS compared with the sham version, but the authors noted that their preliminary findings need to be confirmed in larger studies with long-term follow-up.
“Acupuncture is an exotic therapy, elicits the patient’s active participation, and involves a greater patient—provider interaction, compared with taking a pill,” explained Mao. “Importantly, the results of this trial show that even sham acupuncture—which is effectively a placebo—is more effective than medications. The placebo effect is often dismissed as noise, but these results suggest we should be taking a closer look at how we can best harness it.”
Mao JJ, Bowman MA, Xie SX, et al. Electroacupuncture versus gabapentin for hot flashes among breast cancer survivors: a randomized placebo-controlled trial [published online August 24, 2015]. J Clin Oncol.
Marsha Schmit, RN, BSN, CBCN
Breast Health Navigator
Hurley Medical Center Flint, MI
Treatment-related side effects can impose noncompliance with treatment. Having options that do not create additional side effects is appealing in order to assure patient compliance with recommended therapy.
The recent study comparing electroacupuncture versus gabapentin for hot flashes among breast cancer survivors produced compelling results. In this study, 120 patients were randomized to 1 of 4 groups, two of which received active treatment with either electroacupuncture or gabapentin, while the other two groups received a placebo intervention of sham electroacupuncture or a placebo pill.
Results showed a strong correlation of symptom relief in the acupuncture group and sham acupuncture group compared with the medication/placebo arms of the trial. Additionally, both acupuncture groups reported fewer side effects with much more favorable outcomes than the pill groups.
There are several reasons why this could be the case, including thoughts of positive outcomes, patient—provider interactions, patients being actively involved in their care, and relaxation.
Regardless, it is imperative that consideration and studies of complementary treatments for adverse symptom management continue to be evaluated to improve the quality of life of patients receiving treatment. It is also important that nurses are knowledgeable of these treatment options in order to better support the successful completion of recommended regimens.
Weighing the Benefits of Radiation in Older Women With TNBC
Lauren M. Green
Little is known about the potential benefits of adjuvant radiotherapy in older women diagnosed with triple-negative breast cancer (TNBC), but findings of a retrospective study suggest that the approach may be worth considering for this population. The findings were reported at the 2015 Breast Cancer Symposium held September 25-27 in San Francisco.
The study analyzed findings from the SEER database of 974 women diagnosed with TNBC from 2010-2011 aged ≥70 years treated with lumpectomy for their local, stage T1-2 TNBC with no lymph node involvement. Of the total, 68% of the women (n = 662) received adjuvant radiation therapy.
Survival for those who received lumpectomy plus radiotherapy was 98.2% 23 months after diagnosis versus 85.6% for those who had lumpectomy alone. Breast cancer—related deaths were also more common in the lumpectomy-only group (6%) compared with 1% in the cohort who also had radiation.
“This study suggests that adjuvant radiation therapy may benefit some elderly patients with breast cancer, but a prospective study will be needed to guide treatment decisions,” noted ASCO Expert Harold J. Burstein, MD, PhD, FASCO, in a statement accompanying release of the study. “When selecting treatments for elderly patients, we need to be particularly careful about weighing the benefits and risks.”
When other factors were considered, such as age, tumor size, and other treatment descriptions, the use of adjuvant radiation was associated with an overall 6-fold decrease in any death, as well as death from breast cancer.
“When clinicians treat elderly patients with early-stage, triple-negative breast cancer, they can use these findings to make a more refined decision, with more information, to weigh the risks and benefits of radiation after lumpectomy,” explained lead author Sean Szeja, MD, radiation oncologist, University of Texas Medical Branch in Galveston, in an interview at the symposium. “The benefit from radiation is very substantial, and strong consideration should be given.”
The authors noted, however, that the difference in survival observed between those who did and did not receive adjuvant radiotherapy for their TNBC could be explained by other factors, such as use of adjuvant chemotherapy.
Szeja acknowledged that whether to treat elderly patients with radiotherapy can be a complex decision, due to their age, weight, comorbidities, as well as social factors such as family support. “In addition to these other factors, the life expectancy of the patient is important, too.”
He said that in elderly patients with early-stage TNBC, researchers found that radiation use was fairly widespread—approximately 68% of the time.
Although clinicians may have previously been recommended to hold off on radiation for this population, these findings suggest that the option should be considered more strongly, he added.
Szeja S, Hatch SS. Outcomes associated with adjuvant radiation after lumpectomy for elderly women with T1-2N0M0 triple-negative breast cancer: SEER analysis. J Clin Oncol. 2015 (suppl 28S; abstr 39)
Analysis Shows DCIS Recurrence Rates Decline With Lumpectomy
Lauren M. Green
Results of a retrospective analysis of local recurrence rates among women who opted for lumpectomy to treat their ductal carcinoma in situ (DCIS) show that DCIS recurrence rates have fallen over the last 30 years—especially more recently—findings which may help with patient education efforts aimed at women who are deciding whether to treat their breast cancer with this less invasive approach rather than mastectomy.
The authors suggested that the decline in recurrence rates may be attributable to advances in the quality of mammography, as well as more detailed pathology assessments.
The research, conducted by investigators at Memorial Sloan Kettering Cancer Center (MSK) in New York City, was reported at the 2015 Breast Cancer Symposium held September 25-27 in San Francisco.
The findings are drawn from an analysis of a prospectively maintained database of 2996 women with DCIS who underwent breast-conserving surgery at MSK between 1978 and 2010.
Researchers found that patients with DCIS who were treated more recently (1999-2010) had a 40% lower risk of cancer recurrence than those treated earlier (1978-1998). Five-year recurrence rates fell from 13.6% to 6.6% over the course of these two time periods (hazard ratio [HR], 0.62; P <.0001). This decrease in recurrence rates was limited to women who did not receive radiation therapy.
“Over the past three decades, substantial progress has been made in lowering the risk of breast cancer recurrence after treatment,” said ASCO Expert Harold J. Burstein, MD, PhD, FASCO, in a statement accompanying release of the findings.
When researchers controlled for factors known to affect recurrence, such as increased screening, more frequent use of adjuvant therapies, and wider surgical margins, the significant decline was still evident.
“This study demonstrates that multidisciplinary care, combined with advances in management and detection, is making a tangible difference for women with DCIS,” said Burstein.
Study author Kimberly J. Van Zee of MSK said in an editorial statement that shared decision making with the patient is key to treating DCIS:
“Women with DCIS have several accepted treatment options, ranging from excision alone, excision with radiation, excision with endocrine therapy, and excision with both radiation and endocrine therapy, to mastectomy and even bilateral mastectomy. Discussion of the pros and cons and risks and benefits of each option with each patient is necessary, so that their treatment can be aligned with their individual values.”
Van Zee KJ, Subhedar P, Olcese C, et al. Recurrence rates for ductal carcinoma in situ: analysis of 2996 patients treated with breast-conserving surgery over 30 years. J Clin Oncol. 2015 (suppl 28S; abstr 32).
Survival Not Improved by Adjuvant Bevacizumab in NSCLC
The addition of bevacizumab (Avastin) to adjuvant chemotherapy did not improve overall survival (OS) in patients with surgically resected early-stage non—small cell lung cancer (NSCLC), according to results of the phase III E1505 trial reported during a press conference at the 2015 World Conference on Lung Cancer held in Denver September 6-9. (Abstract 1608)
The phase III trial randomized 1501 patients with NSCLC in a 1:1 ratio to chemotherapy with bevacizumab (n = 752) or without (n = 749). Data showed that OS did not differ between the two arms (hazard ratio [HR], 0.99; 95% CI, 0.81-1.21; P = .93). Median OS was more than 72 months in both cohorts. Similar data was reported with disease-free survival, a secondary endpoint, between the two arms (HR, 0.98; 95% CI, 0.84-1.14; P = .75).
“The study highlights the importance of randomized trials to prove—or disprove—the utility of drugs in different stages of disease,” Heather A. Wakelee, MD, associate professor of medicine (oncology), at Stanford University Medical Center, said in a statement. “With the development of other active agents in metastatic lung cancer, it will be important to investigate them fully in earlier stages and not assume the benefit seen in advanced stage will also be proven in earlier stages, though we can remain hopeful.”
The study enrolled patients between 2007 and 2013 and was conducted by the ECOG- ACRIN Cancer Research Group. Patients were enrolled within 6 to 12 weeks of surgery and were stratified based on the type of chemotherapy they received, histology, stage, and gender. Overall, 28.2% of patients were diagnosed with squamous NSCLC. Patients were diagnosed with stage IB (>4 centimeters; 26.2%), stage II (43.8%), and stage IIIA (30%).
Chemotherapy regimens involved a planned four cycles of cisplatin at 75 mg/m2 every 3 weeks for approximately 3 months with vinorelbine (25%), docetaxel (22.9%), gemcitabine (18.9%), or pemetrexed (33.2%). Patients in the bevacizumab arm received the angiogenesis inhibitor at 15 mg/kg every 3 weeks for 1 year. Post-operative radiation therapy was not permitted.
No unexpected toxicities were found with the addition of bevacizumab; however, there was a significant increase in neutropenia and hypertension. There was no significant difference in treatment-related deaths (2% vs 3%, with chemotherapy and bevacizumab, respectively).
Serious adverse events (AEs) related to bevacizumab included gastrointestinal perforation, neutropenic sepsis, myocardial infarction, gastrointestinal hemorrhage, CNS infarction, and pulmonary hemorrhage. The most common AEs associated with bevacizumab include asthenia, constipation, pain, abdominal pain, upper respiratory infection, headache, hypertension, epistaxis, diarrhea, nausea, dyspnea, vomiting, anorexia, exfoliative dermatitis, proteinuria, and stomatitis.
The study had an 85% power to detect a 21% reduction in the OS HR with a one-sided P value of .025. At an interim analysis, a Data Safety Monitoring Committee recommended that the study should be unblinded with a median follow-up time of 41 months At 84 months from the time of registration, the Kaplan-Meier curves showed nearly a 0.5 overall survival probability, suggesting that approximately 50% of patients remained alive at 7 years. In the SEER database, the 5-year OS in 2007 was noted as 49% for those with stage IA disease and 14% for those with stage IIIA. However, the findings from E1505 suggested a higher figure in both arms of the study.
“I think there are a lot of advancements in what we are able to do to support patients over that time,” Wakelee said regarding the better than expected data. “Part of it could have been selection, as well. The [eligibility requirements] were not any stricter than a lot of the prior trials. I think it is just showing improvements in what we are able to offer patients who get extra treatments.”
Although bevacizumab was shown to not have benefit in the adjuvant setting when combined with chemotherapy, Wakelee said additional steps would be taken following these results, including biomarker analyses.
“This is not the end of the story,” Wakelee said. “We have a significant number of correlates planned. Tissue, blood, and serum were collected from these patients, so analyses will be done. We also have a lot of subsets of interest looking at the patients across the board.”
Samantha Siegel, MSN, APN-C, OCN Advanced Practice Nurse
John Theurer Cancer Center Hackensack, NJ
The diagnosis of lung cancer alone is an incredible burden on both patients and their support system. The treatment plan, which can involve any variation of chemotherapy, radiation, and/or surgery, becomes even more cumbersome and overwhelming. The idea of combination chemotherapy can also be overwhelming. As healthcare professionals, we certainly do not want to add any more pharmacotherapy than is necessary. It would behoove both the patient and healthcare professional to keep the treatment plan as simple as possible.
The findings of this study reveal that bevacizumab does not add to the overall survival of patients receiving adjuvant chemotherapy. Bevacizumab also adds a number of side effects, commonly including bleeding, hypertension, and asthenia. It also may add significantly to the financial burden of the patient and his/her support system. Removing bevacizumab from a chemotherapy regimen makes sense when it does not provide a clear benefit.
However, we must consider that additional studies may show different results. Should a future study show efficacy or an overall survival benefit in patients receiving adjuvant chemotherapy, providers should of course reconsider the addition of bevacizumab. Pending further studies, the deletion of an unnecessary form of pharmacotherapy seems to be most appropriate. Nevertheless, this information should not minimize the importance of bevacizumab in disease states where it has proven efficacy.
Benvacizumab Triplet Improves Survival in Mesothelioma
Jason M. Broderick
Adding bevacizumab to a standard chemotherapy doublet reduced the risk of death by 24% and disease progression by 39% in patients with malignant pleural mesothelioma (MPM), according to results from the phase II/III MAPS trial presented at the 2015 World Conference on Lung Cancer held September 6-9 in Denver. (Abstract 2142)
“The treatment of pemetrexed, cisplatin, and bevacizumab is a new treatment paradigm for patients with malignant pleural mesothelioma,” lead author Arnaud Scherpereel, MD, PhD, head of the Pulmonary and Thoracic Oncology Department and professor at the University Hospital of Lille, France, said in a press conference at the World Lung meeting.
The French Cooperative Thoracic Intergroup (IFCT) phase II/III MAPS trial included 448 chemotherapy-naïve patients enrolled across 73 locations between February 2008 and January 2014. Patients had to have unresectable, histologically confirmed MPM and an ECOG performance status (PS) of 0 to 2 (96.7% had a PS of 0-1).
The median patient age was 65.7 years. Patients with brain metastases, thrombosis, or bleeding were not eligible. All patients were required to receive prophylactic radiotherapy (3 x 7 Gy) prior to initiation of chemotherapy and within 28 days of pleural biopsy.
Patients were randomized in a 1:1 ratio to pemetrexed (500 mg/m2) plus cisplatin (75 mg/ m2) either alone (n = 225) or with 15 mg/kg of bevacizumab (n = 223). All treatments were administered on day 1 of a 21-day cycle for 6 cycles. Following 6 cycles, patients in the experimental arm with disease control continued on maintenance bevacizumab at the same dose and schedule until disease progression or unacceptable toxicity. Crossover between arms was not allowed.
Approximately three-fourths of patients in each arm completed all 6 initial treatment cycles. The median number of treatment cycles was 6 in the control arm and 9 in the bevacizumab arm. Response was assessed with CT scans every 3 cycles in both arms using modified RECIST criteria for mesothelioma.
At a median follow-up of 39.4 months, overall survival (OS) was 18.82 months in the bevacizumab arm versus 16.07 months with chemo- therapy alone. In previous research, median OS with the pemetrexed/cisplatin doublet has been less than13 months in patients with MPM, noted Scherpereel. Median progression-free survival was 9.59 months with bevacizumab versus 7.48 months in the control arm.
Data from the MAPS trial were also presented in June at the 2015 ASCO Annual Meeting (J Clin Oncol. 2015;33 (suppl; abstr 7500). These data showed that rates of grade 3/4 toxicities were slightly higher with bevacizumab at 71.2%, compared with 62.1% in the control arm.
Incidence of hematologic toxicities was similar between arms; however, anemia occurred more frequently in the control arm at 83.5% versus 73.4% in the bevacizumab arm. Grade 3/4 anemia occurred in 13.4% and 7.2% of the control and bevacizumab arms, respectively. Nonhematologic malignancies were also similar between the treatment arms for the most part. However, the bevacizumab arm had higher grade 3/4 rates of hypertension (23.0% vs 0), venous and arterial thromboembolic events (5.8% vs 0.9%), creatinine increase (3.6% vs 1.8%), and hemorrhage (0.9% vs 0).
“Quality of life was preserved in both arms, and bevacizumab did not show a detrimental effect on quality of life, despite the higher toxicity,” said lead investigator Gérard Zalcman, MD, president of the IFCT, when presenting the MAPS results at the ASCO annual meeting.
Most Young Lung Cancer Patients Have Actionable Mutations
Lauren M. Green
A preliminary analysis of an ongoing study shows that most patients diagnosed with lung cancer before age 40 had an increased chance for a targeted genomic alteration which could lead to more effective targeted treatment. The data, which were reported at the 2015 World Conference on Lung Cancer (WCLC) held September 7-9 in Denver, showed that the majority of the participants had metastatic adenocarcinoma, and three-fourths of the tumors had actionable mutations. (Abstract 3632)
The results came from the ongoing Genomics of Young Lung Cancer study. Studies reported at the WCLC suggested that younger patients account for an increasing proportion of lung cancer incidence. Initiated a year ago, the study is enrolling patients at centers in the United States and Europe. Additionally, individuals can register for the study online (https:www.openmednet.org/site/alcmi-goyl) and receive information about the nearest location that can provide the necessary genomic analysis. Barbara Gitlitz, MD, associate professor of Clinical Medicine at the University of Southern California in Los Angeles, said 30 of the first 68 study participants enrolled online and, in the process, helped expand the number of participating centers.
Study investigators have identified seven genomic alterations of interest: EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET. “We felt that our enriched subtype would show an increase in targetable alterations from 35% to 50% and subsequent increase in use of targeted therapy,” said Gitlitz.
The data for the 68 patients enrolled thus far showed a median age at lung cancer diagnosis of 35 years (range, 16-39 years), including 33 men and 35 women. Consistent with the literature on lung cancer, 88% (n = 60) of patients had adenocarcinoma, 10% (n = 7) had squamous-cell tumors, and one patient had small-cell lung cancer. Gitlitz reported that 54 (79%) of the 68 patients had stage IV disease at diagnosis and the remaining patients had stages I-III. In the subset of patients with adenocarcinoma, 50 (74%) had stage IV disease at diagnosis.
Focusing on the 50 patients with stage IV adenocarcinoma, Gitlitz reported that genomic analysis showed that the driver mutation involved ALK in 22 (44%) patients, EGFR in 13 (26%), and ROS1 in three (6%) patients.
In five cases, data were insufficient to determine the driver mutation. The remaining seven (14%) patients had other types of mutations: EGFR-RAD1, EGFR Dup, HER2, ATM, BRCA2, p53/PTEN, and p53. Only one of these mutations occurred in a woman, suggesting a difference between men and women, as 90% of the women in the stage IV adenocarcinoma subgroup had tumors with ALK, EGFR, or ROS1 mutations.
Fosaprepitant Improves Emesis Control in Women Receiving Chemoradiotherapy for Cervical Cancer
Adding fosaprepitant to an antiemetic regimen significantly improved emesis control versus standard care in women receiving radiotherapy and cisplatin for cervical cancer, according to results from the phase III GAND-emesis trial presented at the 2015 European Cancer Congress. (Abstract LBA34)
Adding the neurokinin-1 receptor antagonist to palonosetron and dexamethasone significantly improved the “sustained no emesis rate” versus the two drugs alone, at 76.7% versus 65.1%, respectively.
“Addition of fosaprepitant to palonosetron and dexamethasone provided significantly better control of emesis and nausea over palonosetron and dexamethasone alone in women receiving chemoradiation for cervical cancer,” said lead study author Christina H. Ruhlmann, PhD candidate at Odense University Hospital, Odense, Denmark.
The phase III GAND-emesis trial was an investigator-initiated, multinational, randomized, double-blind, placebo-controlled phase III trial that enrolled 246 chemotherapy- and radiotherapy-naïve women with cervical cancer. Ruhlmann emphasized that patients experiencing emesis or moderate-to-severe nausea within the 24 hours preceding the first dose of study medication were also precluded from participation.
All patients received a regimen of 5 fractions per week of radiotherapy at 2 Gy to the pelvis, plus antiemetic prophylaxis with intravenous palonosetron at 0.25 mg plus oral dexamethasone at 16 mg prior to the administration of cisplatin at 40 mg/m2 given on day 1 weekly for 5 weeks. Both cohorts also received 8 mg of dexa- methasone twice daily on day 2 of each cycle, 4 mg twice daily on day 3, and 4 mg once daily on day 4. The treatment was repeated for 5 weekly cycles. Patients were also allowed additional use of antiemetic rescue medication. In addition to this regimen, patients were randomized to either 150 mg of intravenous fosaprepitant daily or placebo.
Overall, 234 patients (118 in the fosaprepitant arm and 116 in the control arm) received study medication and were eligible for the efficacy evaluation. Patient baseline characteristics were well matched between groups; all patients received median EBRT dose of Gy 50.
The primary endpoint was the no emesis rate sustained over days 1 through 35, and secondary endpoints were complete response (CR), nausea, and safety. Efficacy assessments were made daily and safety assessments were made on a weekly basis.
The cumulative emasis incidence over the course of the trial was lower with fosaprepitant. During weeks 1, 2, 3, 4, and 5, no emesis was sustained by 86%, 78%, 73%, 69% and 66% of patients receiving added fosaprepitant compared to 78%, 66%, 59%, 53%, and 49%, respectively, of patients receiving antiemetics only—an overall difference of 17%. CR, defined as no emesis and no use of rescue antiemetics, within 24 hours after initiation of therapy, was achieved by 92% of fosaprepitant patients versus 86% of the placebo arm. CR at 120 and 168 hours post therapy was 74% and 71% versus 64% and 59% in the respective cohorts.
At the end of cycle 1 (168 hours) the rates of no nausea were 42% with fosaprepitant compared with 25% with placebo.
CR over days 1 to 35 was achieved by 51% of fosaprepitant patients versus 33% of placebo patients (P = .005), and no nausea was sustained over the same duration by 14% versus 8% of fosaprepitant and placebo patients, respectively.
No statistically significant difference was seen between the adverse event (AE) profiles of the cohorts. The most commonly reported (affecting ≥10 patients) AEs were loss of appetite, fatigue, headache, dizziness, hearing impairment, tinnitus, and nervous system disorders.
Discussant Stein Kaasa, MD, a palliative care expert and head of the Cancer Clinic at Trondheim University Hospital in Norway, who was not involved in the study, remarked that the findings were, “Not only statistically, but also clinically significant. Most studies on emesis control are done with chemotherapy, although we know that nausea and vomiting are highly prevalent when radiation is delivered to the abdomen.”
Indoor Pesticides Linked to Childhood Blood Cancers
Children exposed to residential pesticides are at a higher risk of developing pediatric hematopoietic cancers, a new study has found.
Researchers from the Harvard T.H. Chan School of Public Health reviewed 16 previous studies of childhood exposure to indoor insecticides to examine a possible association with pediatric cancer. For this meta-analysis, published online September 14, 2015 in Pediatrics, investigators found that indoor insecticides were associated with a significant increase in the risk of childhood leukemia (odds ratio [OR] = 1.47; 95% CI, 1.26—1.72; I2 = 30%) and childhood lymphomas (OR = 1.43; 95% CI, 1.15—1.78; I2 = 0%).
Exposure to herbicides was also associated with a significant increase in the risk of leukemia (OR = 1.26; 95% CI, 1.10—1.44; I2 = 0%), but no association was found between outdoor residential insecticides and an increased risk of childhood leukemia or lymphoma.
There was also no statistically significant association between home pesticides and childhood brain tumors.
The authors note that although current data do not establish a critical exposure period for the occurrence of childhood cancers, development is probably multifactorial and may include gene—environment interactions. They acknowledge that the small number of studies examined is a major limitation of the analysis, and additional information is needed to confirm an association between indoor pesticide exposures and pediatric cancer. Still, the researchers conclude that preventive measures should be taken to reduce childhood exposure to indoor pesticides:
“While the research community is working toward a better understanding of the causality of pesticides in various childhood diseases, more and more pesticides are being used in farming, in landscape maintenance, and in the home. Therefore, public health policies should be developed to minimize childhood exposure to pesticides in the home...In the meantime, parents, school and daycare teachers and healthcare providers can learn about common pesticide types and labeling information and can stay aware of the short- and long-term effects of these.”
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