ASCO 2018 Preview

With about two weeks to go until the 2018 ASCO Annual Meeting, a pre-meeting press cast featured abstracts of interest that are “just the tip of the iceberg,” said ASCO Chief Medical Officer Richard L. Schilsky, MD. Topics covered included a practice-changing regimen for T-cell malignancies, shorter course trastuzumab for early HER2-positive breast cancer, cost-effectiveness of next-generation sequencing, mobile sensor technology for reducing symptom severity in head and neck cancer survivors, and alarmingly low rates of lung cancer screening in heavy smokers and former heavy smokers. Here are recaps of the major findings.

T-Cell ALL and T-Cell-LL (Abstract 10500)

The largest randomized study ever conducted in T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic leukemia (T-LL) showed the highest overall survival (OS) and disease-free survival (DFS) rates reported to date in 1,545 newly diagnosed children and young adults with these relatively uncommon malignancies. Using standard chemotherapy (a regimen called COG-augmented Berlin-Frankfurt-Munster [aBFM] chemotherapy) plus escalated dose methotrexate or high dose methotrexate, 4-year OS was 90.2% and 4-year event-free survival (EFS) was 84.1%.

In a group of 659 patients at moderate to high risk of recurrence, the addition of nelarabine to standard aBFM chemotherapy achieved 4-year disease-free survival (DFS) of 88% versus 83% in patients not randomized to nelarabine (P=.0450). Patients also received cranial radiation prophylactically or therapeutically.

Patients with T-LL (6% of the total patient population) did not benefit from nelarabine’s addition, but DFS was more than 85% at 4 years in this group of patients.

Patients randomized to receive aBFM plus escalating doses of methotrexate fared better than those treated with aBFM plus high-dose methotrexate: 4-year DFS 89.8% versus 78%, respectively. The arm with the best outcome was nelarabine plus escalated methotrexate, with a 4-year DFS of 91%.

In a small group of 43 patients who failed induction chemotherapy and were non-randomly assigned to high-dose methotrexate plus nelarabine, 4-year DFS beat historical controls: 54.3% were alive with no signs of disease in this study versus 20% of historical controls.

“These outstanding results suggest that nelarabine should become a new standard of care for newly diagnosed T-ALL and T-LL,” said lead author Kimberly Dunsmore, MD, Virginia Tech Carillon School of Medicine, Roanoke, VA.

These results apply to nelarabine when used with aBFM, which is commonly used at pediatric oncology centers in the U.S. They are not generalizable to other regimens, noted experts.

Shorter Course of Trastuzumab (Abstract 506)

A 6-month course of trastuzumab was non-inferior to the current standard of 12 months in the phase III randomized PERSEPHONE trial that included 4,088 women with early-stage, HER-2-positive breast cancer. Four-year DFS was 89.4% in women who received 6 months of trastuzumab versus 89.8% with 12 months of therapy, an absolute difference of 0.4%. Shorter-course trastuzumab appeared to improve cardiac safety. Four percent of women treated with 6 months of therapy stopped treatment due to cardiac events, compared with 8% of the 12-month arm (P<.0001).

“The Persephone trial’s researchers worked closely with patient advocates. Everyone involved in the study is very excited by these results,” said lead author Helena Earl, MD, professor at the University of Cambridge, U.K. “We are confident that this will mark the first steps towards a reduction of the duration of trastuzumab in many women with HER2-positive breast cancer.”

Longer follow-up is needed to establish survival for both arms before 6 months of trastuzumab can be considered standard of care.

PERSEPHONE, funded by the National Institute for Health Research in the U.K., is the largest trial to date to analyze the impact of shorter course trastuzumab in this setting.

Women enrolled in PERSEPHONE were also treated with chemotherapy during the trial. They were followed for a median of 5+ years. Next steps are to determine the impact of treatment length on quality of life, and cost-effectiveness of the two schedules.

“This study establishes the non-inferiority of 6 months of trastuzumab. A shorter course of therapy can reduce the number of patients who stop treatment for cardiotoxicity by half and will reduce cost as well,” said ASCO President Bruce E. Johnson, MD, who moderated the press cast.

Next-Generation Sequencing More Cost-Effective (Abstract 9031)

Genomic testing is now standard of care for non-small cell lung cancer (NSCLC), but what is the best way to do it?

Next-generation sequencing (NGS) of patients with metastatic non-small cell lung cancer (NSCLC) to test for all known cancer-related genes at diagnosis was more cost-effective and provided faster results compared with testing for one or a limited number of genes at a time, according to an economic model based on Medicare and commercial health plans with 1 million hypothetical members.

In the model, when compared with three other testing options, NGS saved between $1.4 million and $2.1 million for Medicare and between $127,402 and $250,842 for commercial insurance providers.

“The field of lung cancer treatment is moving at a rapid pace, and we need to fully characterize genomic changes to determine the best treatment for patients shortly after they are diagnosed. Today, many treatment decisions are guided by the presence or absence of certain genetic changes in a patient’s tumor, and I expect that several more genes will be identified in the near future. Therefore, it becomes even more imperative to find a cost-effective gene test that can quickly identify a large number of gene mutations that can be targeted by treatments,” stated lead author Nathan A. Pennell, MD, PhD, co-director of the Cleveland Clinic Lung Cancer Program.

Currently, there is no accepted standard for genetic testing in lung cancer as well as the timing of such tests. The model was designed to determine which gene testing approach is most cost-effective and time-efficient.

Known gene alterations in NSCLC that are targetable include EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1. EGFR, ALK, ROS1, BRAF are targetable with approved therapies. Investigational agents are targeted to the other generic changes, and newer tests also look at PD-L1 expression to predict whether a tumor will respond to immunotherapy.

The model compared one of four different approaches: upfront NGS (testing for all NSCLC-related genes and KRAS); sequential tests for one gene at a time; exclusionary KRAS test, followed by sequential testing for changes in other genes if KRAS was not mutated and no other tests if KRAS was mutated; a “hotspot” panel test for EGFR, ALK, ROS1, and BRAF, followed by either single-gene testing or NGS testing.

NGS and Hotspot panel had faster turnaround times, enabling patients to initiate appropriate therapy 2.8 and 2.7 weeks earlier, respectively. Additionally, NGS identified a higher percentage of patients with targetable alterations compared with the other three strategies.

Remote Technology to Monitor Head and Neck Cancer Symptoms (Abstract 6063)

Head and neck cancer patients treated with radiation have a high symptom burden and are at increased risk for dehydration. Using a mobile and sensor technology called CYCORE, to monitor patients’ symptoms remotely, reduced the severity of treatment- and cancer-related symptoms when compared with usual care (weekly visits to the radiation oncologist), according to a federally-funded, randomized clinical trial that included 357 people with head and neck cancer treated with radiation.

CYCORE includes a Bluetooth-enabled weight scale, Bluetooth-enabled blood pressure cuff, and mobile tablet with a symptom-tracking app that sent information directly to the physician’s office Monday through Friday. Patients who used this technology had lower symptom severity compared with patients who had standard weekly visits with their radiation oncologist.

Daily monitoring of wellbeing enabled physicians to detect symptoms earlier and respond more rapidly compared with usual care.

“Our study generated evidence on how newer technologies can be integrated into cancer care relatively easily and improve patient outcomes without interfering too much in a person’s daily life. This study was done during a rather intense period in the patients’ care for head and neck cancer. The system helped physicians to provide valuable support that ultimately resulted in lower symptom severity,” said lead author Susan K. Peterson, PhD, professor at the University of Texas MD Anderson Cancer Center, Houston, TX.

Patients were randomized 1:1 to CYCORE or standard weekly visits to their radiation oncologist. At the start of radiation therapy, self-reported health severity scores were similar between the two groups. The MD Anderson Symptom Inventory was used to track symptom severity, and patients were weighed and had blood pressure monitoring daily.

After completion of radiation therapy, CYCORE participants reported lower mean scores for general symptoms versus usual care participants (2.9 versus 3.4, respectively) on a zero to 10 scoring system for symptom severity (i.e., 10=most severe). CYCORE participants also had lower mean scores for specific head and neck cancer symptoms (4.2 versus 4.8, respectively).

Six to 8 weeks after completion of radiation therapy, these benefits persisted in favor of CYCORE monitoring. Mean age of patients was 60 years, with a range of 25 to 86 years. Adherence to daily monitoring was 80%.

“CYCORE was feasible in older patients and we had good adherence,” Dr. Peterson said. “This type of monitoring can provide timely information for clinical decision-making and can be expanded to community cancer centers.”

“This study adds to the growing body of evidence that integrating patient-reported outcomes can lead to reduced complications in a wide variety of participants,” said ASCO President, Dr. Johnson.


Lung Cancer Screening Rates Abysmal (Abstract 6504)

Only about 1.9% of almost 8 million current and former heavy smokers underwent low-dose computed tomography (LDCT) screening screened for lung cancer during 2016, according to an analysis of 1,800 lung cancer screening sites. These rates show that the 2015 screening recommendations from the U.S. Preventive Services Task Force (USPSTF) recommending LDCT for current and heavy smokers aged 55 to 80 years are largely being ignored by providers and patients.

Nationwide, a total of 1,796 accredited screening centers could have screened 7,612,975 eligible current and heavy smokers, but only 141,260 people received LDCT screenings (1.9%). By contrast, about 65% of women age 40 or older had a mammography over the same time period.

Screening rates were lowest in the West (1%), followed by the South (1.6%). The Northeast had the highest screening rate (3.5%) and the Midwest the second highest (1.9%).

“Lung cancer screening rates are much lower than screening rates for breast and colorectal cancers, which is unfortunate. It is unclear if the screening deficit is due to low provider referral or perhaps patient psychological barriers from fear of diagnosis. Lung cancer is unique in that there may be stigma associated with screening, as some smokers think that if cancer is detected, it would confirm that they have made a bad lifestyle choice,” said lead author Danh Pham, MD, medical oncologist at the James Graham Brown Cancer Center, University of Louisville, KY.

“Effective screening can prevent 12,000 premature lung cancer deaths each year,” Dr. Pham stated.

John McCleery



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