Quick Takes From Original Research Presented at the 2018 NCCN Annual Conference


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THE QUANTITY of original research presented at the National Comprehensive Cancer Network® (NCCN®) Annual Conference has been growing, and at the 2018 meeting, 121 researchers presented their work. The ASCO Post captured some of the findings for this report. 

Blood Markers Correlate With Anti–PD-1 Outcomes 

SEVERAL ROUTINE peripheral blood biomarkers correlated with clinical outcomes in non–small cell lung cancer (NSCLC) patients treated with antibodies targeting programmed cell death protein 1 (PD-1).1 The findings came from a retrospective analysis of 157 patients with advanced NSCLC who received treatment with nivolumab (Opdivo) and pembrolizumab (Keytruda). 

Researchers looked at white blood cell counts, absolute neutrophil counts, absolute lymphocyte counts, absolute neutrophil count–to–absolute lymphocyte count ratios, absolute eosinophil counts, platelet counts, and myeloid-to-lymphoid ratios at baseline and throughout treatment. The aim was to determine if any of these simple biomarkers might predict for treatment success. 


“Our analysis shows that a readily available complete blood count can help predict response to immunotherapy and outcomes.”
— Aixa Soyano, MD

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Aixa Soyano, MD, and colleagues from the Mayo Clinic in Jacksonville, Florida, reported significant improvements in overall and/ or progression-free survival for several of these baseline factors: 

  • Absolute neutrophil count/absolute lymphocyte count ratio < 5.9 vs ≥ 5.9 (P = .004 for overall survival and P = .005 for progression-free survival) 
  • Absolute neutrophil count < 7.5 vs ≥ 7.5 K/μL (P = .012 for overall survival) 
  • Myeloid/lymphoid ratio < 11.3 vs ≥ 11.3 (P < .001 for overall survival). 

For example, they found approximately 70% of patients with absolute neutrophil count/absolute lymphocyte count ratio < 5.9 were alive at 7 months, compared to about 50% with absolute neutrophil count/absolute lymphocyte count ratio ≥ 5.9 (P = .004). 

“Our analysis shows that a readily available complete blood count can help predict response to immunotherapy and outcomes. The potential predictive value of these biomarkers might help with risk stratification and treatment strategies,” the researchers concluded. 

Antiemetogenic Guidelines Frequently Not Followed 

FEWER THAN 50% of patients treated with highly emetogenic chemotherapy received guideline-recommended prophylaxis, (ie, a regimen that included an upfront NK1 receptor antagonist), according to Eric J. Roeland, MD, of the Massachusetts General Hospital Cancer Center, and colleagues.2 


“These findings emphasize the importance of…streamlining practices to improve compliance with evidence-based antiemetic guideline recommendations.”
— Eric J. Roeland, MD

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The analysis included 111,497 chemotherapy-naive patients receiving highly emetogenic chemotherapy, of whom 35% received carboplatin, 24% received an anthracycline plus cyclophosphamide (AC), and 18% received cisplatin. From 2011 to 2016, guideline-recommended prophylaxis was given to 45% of all highly emetogenic chemotherapy recipients for their initial cycle (an NK1 receptor antagonist plus a 5-HT3 receptor antagonist with or without dexamethasone). Compliance rates were lower for carboplatin recipients (26%) than for AC recipients (71%) or cisplatin recipients (72%). 

“The discrepancy seen between the carboplatin-treated patients and cisplatin-treated patients is likely due to the perception that this chemotherapy agent was considered to be moderately [not highly] emetogenic by most antiemetic treatment guidelines until 2017,” the authors suggested. 

“It is critical to aggressively prevent chemotherapy-induced nausea and vomiting upfront. Otherwise, patients experience a four- to fivefold increase in the chance of nausea and vomiting in subsequent cycles,” per Dr. Roeland. The most common reason (50%) for noncompliance was use of a 5-HT3 receptor antagonist [alone] with or without dexamethasone, and this was consistent across all chemotherapy regimens. Interestingly, most patients in this category received an NK1 receptor antagonist in a subsequent cycle. 

Compliance with the guidelines improved between 2011 and 2016 by around 1.7% a year. However, it declined among patients aged 70 years or older. 

“These findings emphasize the importance of … streamlining practices to improve compliance with evidence-based antiemetic guideline recommendations for upfront prophylaxis with an NK1 receptor antagonist triplet regimen in the [highly emetogenic chemotherapy] setting,” the researchers said. 

MGMT Methylation Status Important in Glioblastoma 

A RETROSPECTIVE study from the Cleveland Clinic demonstrated that molecular markers had an impact on progression-free survival in glioblastoma O6-methylguanine-methyltransferase (MGMT)-methylated patients, though they were not associated with overall survival.3 


“At recurrence, MGMT methylation status can determine individualized treatment.”
— Bicky Thapa, MD

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Bicky Thapa, MD, a resident at Cleveland Clinic, led a retrospective analysis of 288 patients with recurrent glioblastoma treated between 2012 and 2017. Outcomes were analyzed for three cohorts of patients with molecular markers, such as epidermal growth factor receptor (EGFR) amplification (found in 43%), MGMT promoter methylation (38%), and isocitrate dehydrogenase-1 (IDH1) mutation (7.4%). 

After recurrence, 26% of patients underwent surgery, 11% had radiation therapy, and 72% had chemotherapy. Of 184 patients receiving chemotherapy, 34 were treated with lomustine (Gleostine) alone, 81 were treated with bevacizumab (Avastin) alone, 18 were treated with both drugs, and 81 were enrolled in clinical trials. 

Patients with MGMT methylation had a significantly longer progression-free survival than nonmethylated patients: 9.0 vs 5.5 months (hazard ratio [HR] = 0.59; P < .001). The median progression-free survival for all patients was 6.5 months. EGFR and IDH1 status was not significantly associated with progression-free survival, nor were any molecular markers associated with overall survival. 

Treatment with bevacizumab was also associated with either a lower risk of recurrence or an increase in progression-free survival in all three cohorts of patients, but especially in MGMT-methylated patients, Dr. Thapa reported, noting that patients tend to rebound after bevacizumab is stopped. 

“At recurrence, MGMT methylation status can determine individualized treatment,” Dr. Thapa said. 

Check for Vitamin B12 Deficiency in Patients With Cancer 

CANCER PATIENTS are likely to have insufficient levels of vitamin B12, raising concerns about the risks associated with peripheral neuropathy, researchers reported at the NCCN conference.4 

Vitamin B12 is an essential cofactor in several biochemical pathways related to neurologic function, and its deficiency is a predisposing condition for the development of chemotherapy-induced peripheral neuropathy. Chemotherapy itself may also precipitate B12 deficiency through poor absorption, thereby further predisposing patients to neuropathy. 

Paulo Andre Fernandes, MS, a PharmD candidate at Nova Southeastern University in Fort Lauderdale, Florida, and colleagues assessed vitamin B12 levels among patients with cancer as compared to the general U.S. population using data from the National Health and Nutrition Examination Survey (NHANES). The subjects were cancer patients not taking B12 supplementation, cancer patients taking oral vitamin B12 (1,000 μg/d), and patients without cancer (controls). 

“If a patient is deficient [in vitamin B12] and starts on chemotherapy that can produce neuropathy, then the patient is at greater risk for neuropathy.”
— Paulo Andre Fernandes, MS

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The analysis showed that vitamin B12 levels averaged 609 pg/ mL among controls and 501 pg/mL among cancer patients not taking supplements, which are in the low-normal range. In contrast, cancer patients taking supplements averaged 1,636 pg/ mL, showing the power of supplementation to enhance B12 levels, Dr. Fernandes reported. Although cancer patients not on supplements still had levels within the normal range, chemotherapy may diminish these levels, he pointed out. 

“The problem is clinicians often don’t ask about or test for vitamin B12 levels before chemotherapy. If a patient is deficient [in vitamin B12] and starts on chemotherapy that can produce neuropathy, then the patient is at greater risk for neuropathy,” he explained. ■

DISCLOSURE: Drs. Soyano and Thapa and Mr. Fernandes reported no conflicts of interest. Dr. Roeland is a consultant for Helsinn. 

REFERENCES 

1. Soyano AE, Dholaria B, Marin-Acevedo J, et al: Peripheral blood biomarkers correlate with clinical outcome in advanced non-small cell lung cancer patients treated with anti-PD1 antibodies. 2018 NCCN Annual Conference. Poster 75. Presented March 24, 2018

2. Roeland EJ, Ruddy KJ, LeBlanc TW, et al: Gaps in compliance with current antiemetic guidelines for highly emetogenic chemotherapy. 2018 NCCN Annual Conference. Poster 22. Presented March 24, 2018

3. Thapa B, Bellamkonda S, Migdady I, et al: Impact of the molecular marker and treatment on progression-free survival in recurrent glioblastoma: A retrospective tertiary care center analysis. 2018 NCCN Annual Conference. Poster 99. Presented March 24, 2018

4. Fernandes PA, Ibrahim M: Evaluation of vitamin B12 levels within cancer patients in the United States. 2018 NCCN Annual Conference. Poster 102. Presented March 23, 2018


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