Transoral robotic-assisted surgery (TORS), following chemotherapy and neck resections, is an effective model for the definitive treatment for oropharyngeal squamous cell carcinoma (OPSCC) while avoiding the adverse effects of radiation. These results were presented at the 2018 American Society of Clinical Oncology Annual Meeting, June 1 to 5, in Chicago, Illinois.

According to the National Cancer Institute, incidence of oropharyngeal cancer has been on the rise in the United States, and the growing number of human papillomavirus (HPV) infections might be responsible. With over 50,000 cases estimated in 2018, oropharyngeal cancer is expected to lead to more than 10,000 deaths this year.

“The standard of care for OPSCC includes chemoradiation or surgery with adjuvant radiation,” said Robert S. Siegel, MD, George Washington University School of Medicine and Health Sciences, and a senior investigator for the study. He explained that while the treatments are successful 80% to 90% of the time in curing oropharyngeal cancer and 90% of the time in HPV oropharyngeal cancer, radiation treatment can be harsh and can significantly affect morbidity. Long-term effects of radiation treatment can include gum and dental disease, change in taste, difficulty with swallowing, and others.

“We therefore assessed the efficacy of a 2-drug induction regimen, followed by TORS and neck dissection for locally advanced OPSCC,” Siegel said.

Siegel said that with this treatment, the risk of distal disease is diminished and surgery is easier. “Additionally, TORS is more effective than older surgical techniques, with less tissue damage and quicker recovery,” he added.

The single-arm phase 2 study recruited treatment-naive stage III or IVA patients with a diagnosis of OPSCC who had an Eastern Cooperative Oncology Group score <2. The treatment plan included induction chemotherapy with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 every 21 days for 3 cycles. Tumor shrinkage was examined after each cycle. If the primary tumor was ≥80% smaller, patients were scheduled for TORS and neck dissection(s). At postoperation visits, flexible laryngoscopy, blood tests, and imaging with positron emission tomography/computed tomography and/or magnetic resonance imaging were done.

The study outcomes that were evaluated included short- and long-term toxicities, progression-free survival, overall survival, and quality of life (QOL).

Of the 20 patients who met the inclusion criteria and were treated, 19 were male, 17 were Caucasian, and 19 were HPV-positive; median age at diagnosis was 57 years. Thirteen patients had a tumor in their tonsil and 7 at the base of their tongue. Three patients were stage III, and 17 were stage IVA.

The study found that tumor size was reduced by 53.4% after the first induction cycle, 80% after the second, and 90.5% after the third. Therefore, all patients were eligible for surgery, Siegel said. Pathologic complete response (CR) of the primary site occurred in 15 of the 20 patients, and CR among lymph node neck dissections occurred in 13 patients. CR was noted in 12 of 20 patients.

The pre- versus posttreatment QOL scores did not change much: Fourteen patients had very good to excellent QOL at baseline, while 15 patients had good to excellent QOL following treatment.

“At a mean follow-up of 22 months, 18 patients are alive and disease-free,” Siegel said. Three patients who had a recurrence an average of 2.2 months after surgery were treated with salvage chemoradiation therapy, he said. Two of three patients who had metastatic disease died, and all 3 had positive lymph node disease at surgery.

Siegel concluded by stating that induction chemotherapy with TORS and neck dissection can be an alternative for standard chemoradiation in patients who are HPV-positive. He recommends chemoradiation as an option for patients whose tumors do not shrink by 8% or more after induction chemotherapy and who have at least 1 lymph node positive for disease following surgery.

Siegel RS, Rafei H, Joshi A, et al. Phase II study: induction chemotherapy and transoral surgery as definitive treatment (Tx) for locally advanced oropharyngeal squamous cell carcinoma (OPSCC): a novel approach. 

. 2018;36(suppl; abstr 6004). http://abstracts.asco.org/214/Abst- View_214_230487.html.

Articles

Evidence-Based Oncology

Results presented at the 2018 American Society of Clinical Oncology's Annual Meeting found that transoral robotic-assisted surgery (TORS), following chemotherapy and neck resections, is an effective model for the definitive treatment for oropharyngeal squamous cell carcinoma (OPSCC) while avoiding the adverse effects of radiation.

Robotic Surgery Complements Chemotherapy, Safer Than Radiation, in Oral Cancer

During the 2018 American Society of Clinical Oncology’s (ASCO) Annual Meeting, researchers presented findings on 3 biosimilar trastuzumab products: Samsung Bioepis’ SB3, Agmen’s ABP 980, and Biocad’s Herticad.

One-year safety and survival data for SB3 support biosimilarity

SB3, which is approved in the European Union as Ontruzant and is under review by the FDA, was the subject of a report on safety and survival data from patients with HER2-positive early or locally advanced breast cancer. In a clinical trial,

 patients received either SB3 or the reference trastuzumab and had follow-up of at least 12 treatment-free months after 12 cycles of neoadjuvant-adjuvant therapy.

In total, 367 patients were randomized to receive 8 cycles of either SB3 (n = 186) or the reference trastuzumab (n = 181) in the neoadjuvant setting with chemotherapy. Patients then underwent surgery and another 10 cycles of SB3 or the reference trastuzumab.

Patients were followed up every 6 months to observe the incidence of symptomatic congestive heart failure, asymptomatic significant left ventricular ejection fraction (LVEF) decrease, cardiac events, event-free survival (EFS), and overall survival (OS). The median follow-up from initiation of the study was 30.1 months for the SB3 arm and 30.2 months for the reference arm.

During the 1-year follow-up, the incidence of asymptomatic significant LVEF decrease was similar in the SB3 (n = 1) and reference groups (n = 2), and no significant cardiac conditions or cardiac-related death were reported.

Eight patients in the SB3 group and 14 in the reference group experienced disease recurrence, progression, or death. In the SB3 arm, there was 1 patient death, and in the reference arm, there were 3 patient deaths. At 24 months, EFS rates (SB3, 96.7%; reference, 94.3%) and OS rates were comparable between groups (100.0% and 99.4%, respectively).

These results, say the authors, further support the biosimilarity of SB3 with its reference.

Central evaluations from LILAC further support clinical equivalence of ABP 980 and reference trastuzumab

One day after Amgen revealed that the FDA had issued a complete response letter for its ABP 980 (which was authorized for marketing in Europe under the name Kanjinti in May 2018), researchers reported results of a pathologic complete response (pCR) analysis based on a central laboratory evaluation of tumor samples collected in the phase 3, randomized, multicenter, double-blind, active-controlled LILAC study that compared ABP 980 to reference trastuzumab in patients with HER2-positive early breast cancer.

 Results from a local labora- tory evaluation were previously reported.

In the LILAC study, 725 patients were randomized to receive either the biosimilar (n = 696) or the reference trastuzumab (n = 338) plus paclitaxel after run-in chemotherapy. The coprimary endpoints were risk difference (RD) and risk ratio (RR) of pCR adjusted for baseline covariates in breast tissue and axillary lymph nodes. Clinical similarity of the trastuzumab products was supported if the 2-sided 90% CIs were within the equivalence margin for RD (—13% to 13%) and RR (0.759-1.318). Each sample was evaluated by 2 independent central pathologists.

The researchers report that, based on central review, pCR was achieved in 47.8% of patients receiving ABP 980 and 41.8% of those receiving the reference product. The RD was 5.8% (90% CI, —0.5 to 12.0%), and the RR was 1.14 (90% CI, 0.993- 1.312). Both the RD and RR fell within the prespecified equivalence margins.

The researchers say that the results of the central evaluations further support the clinical equivalence of the biosimilar and its reference and the feasibility of including central laboratory review of pCR rates in a large, multicenter, multinational studies.

Biocad’s Herticad reduced the cost of trastuzumab therapy by 75%

Biocad’s Herticad, which is approved for use in Russia, has been available since 2016, and new research reports on the effectiveness, safety, and economics of using the biosimilar in clinical practice.

Researchers conducted a study that included 55 women with stage II or stage III HER2-positve breast cancer who were treated at Russia’s National Research Cancer Center from March 2016 to December 2017. All patients received neoadjuvant chemotherapy together with the biosimilar trastuzumab, after which the patients had surgery with an assessment of pCR.

The rate of pCR was 55.6% in the breast and 45.8% in the breast and lymph nodes, and was similar in patients with primary-operable and locally advanced disease. There were no reports of treatment-associated cardiac dysfunction in any of the patients, nor were there any infusion-related reactions.

The cost to provide neoadjuvant therapy with trastuzumab decreased 75% during the study period by using the biosimilar, and the researchers report that the biosimilar provides an economically reasonable option that is both safe and effective.

Pivot X, Bondarenko I, Nowecki Z, et al. Additional one-year follow-up study to evaluate safety and survival in patients who have completed neoadjuvant-adjuvant treatment with SB3 (trastuzumab biosimilar) or reference trastuzumab in HER2-positive early or locally advanced breast cancer. 

. 2018;36(suppl; abstr e12631). abstracts.asco.org/214/AbstView_214_222137.html.

Kolberg HC, Tomasevic Z, Demetriou G, et al. Efficacy analyses of central laboratory pCR results from the LILAC study comparing the biosimilar ABP 980 and trastuzumab. 

. 2018;36 (suppl; abstr 583). abstracts.asco.org/214/AbstView_214_229787.html.

Kolyadina IV, Ganshina I, Zhukova L, et al. The effectiveness, safety and economic rationality of the neoadjuvant chemotherapy with biosimilar of trastuzumab in HER2+ breast cancer in Russian clinical practice. 

l. 2018;36(suppl; abstr e12656). abstracts.asco.org/214/AbstView_214_224617.html.

Researchers Report Findings on Three Biosimilar Trastuzumab Products

Nearly Half of Patients With Metastatic CSCC Respond to Fast-Tracked Cemiplimab

After taking the programmed death-1 inhibitor cemiplimab for an average of close to 8 months, nearly half of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) responded to treatment in a phase 2 study. A median duration of response had not been reached, however, according to results presented June 4, 2018, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

The results were simultaneously published in the New England Journal of Medicine.

 The journal featured both reports of the expansion cohort from phase 1, which saw a response from 13 of 26 patients (50%; 95% CI, 30%-70%) as well as results from phase 2, which reported responses from 28 of 59 patients.

“The study of cemiplimab for the treatment of advanced cutaneous squamous cell carcimona was underpinned by the recognition that a high mutation burden may render these tumors sensitive to effector T cells in the context of immune checkpoint blockade,” the authors write.

The study of 54 men and 5 women, with an average age of 71 years (range, 38-93 years), involved a 3-mg/kg dose given intravenously every 2 weeks. Tumor measurements were performed every 8 weeks. Overall response rate (ORR) was the primary endpoint, and duration of response was the key secondary endpoint.

The FDA has already granted priority review status to cemiplimab, which is being developed by Regeneron and Sanofi. A decision on the biologics license application is expected by October 28, 2018.

CSCC, or skin cancer, is very common in the United States, and most often it is treatable. But in 5% of the cases, it becomes metastatic, and there is no standard of care for this form of the disease. Thus, cemiplimab would fill a significant unmet need for patients with mCSCC. At ASCO 2017, Regeneron presented promising phase 1 results that resulted in the FDA’s earlier designation of cemiplimab as a breakthrough therapy in this indication.3 Results presented this year include data through October 27, 2017.

At the time of data cutoff, patients had been followed for an average of 7.9 months (range, 1.1-15.6 months). ORR, as measured by an independent review team examining patient scans, was

47% (95% CI, 34%-61%). The rate of durable disease control was 61% (95% CI, 47%-74%), with 4 complete responses and 24 partial responses. The average time to initial response was 1.9 months.

Of the 28 patients who had a response, the duration of response exceeded 6 months for 57%, and 82% still had a response and were taking cemiplimab at the time of the data cutoff.

The most common adverse events (AEs) were diarrhea (27%), fatigue (24%), and nausea (17%). The paper reported 25 AEs of grade 3 or higher, including 17 that were serious and 3 that led to discontinuation of treatment; 3 were associated with an outcome of death. The study’s authors said the side effects observed were typical among patients treated with checkpoint inhibitors.

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“The strong results seen with cemiplimab are noteworthy given that advanced CSCC is a very serious condition that currently has no approved treatments once surgery is no longer an option,” Michael R. Migden, MD, co-lead author and associate professor in the Departments of Dermatology and Head and Neck Surgery at The University of Texas MD Anderson Cancer Center, said in a statement. “Advanced CSCC tumors were shown to be responsive to cemiplimab in both metastatic and locally advanced patients, with the results being clinically meaningful and consistent between the phase 1 and phase 2 trials.”

Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma [published online June 4, 2018]. 

FDA to conduct priority review of cemiplimab as a potential treatment for advanced cutaneous squamous cell carcinoma [press release]. Paris, France, and Tarrytown, NY: Sanofi; April 30, 2018. news.sanofi.us/2018-04-30-FDA-to-Conduct-Priority-Review-of-Cemiplimab- as-a-Potential-Treatment-for-Advanced-Cutaneous-Squamous-Cell-Carcinoma. Accessed June 4, 2018.

Harris J. FDA grants cemiplimab breakthrough designation for CSCC. OncLive® website. onclive.com/web-exclusives/fda-grants-cemiplimab-breakthrough-designation-for-cscc. Published September 8, 2017. Accessed June 4, 2018.

Rischin D, Migden MR, Chang A, et al. Primary analysis of phase 2 results for cemiplimab, a human monoclonal anti-PD-1, in patients with metastatic cutaneous squamous cell carcinoma (mCSCC). 

 2018;36(suppl; abstr 9519). meetinglibrary.asco.org/ record/159083/abstract.

 publishes pivotal cemiplimab trials showing positive results in advanced cutaneous squamous cell carcinoma [press release]. Paris, France, and Tarrytown, NY: Sanofi; June 4, 2018. news.sanofi.us/2018-06-04-New-England-Journal-of- Medicine-publishes-pivotal-cemiplimab-trials-showing-positive-results-in-advanced-cutaneous-squamous-cell-carcinoma. Accessed June 4, 2018.

KEYNOTE-042 Confirms First-Line Pembrolizumab Superior to Chemotherapy in PD-L1— Low Advanced NSCLC

A late-breaking abstract presented on June 3 at the 2018 American Society of Clinical Oncology Annual Meeting confirmed that pembrolizumab significantly improved the primary end point of overall survival (OS) over plati- num-based chemotherapy in treatment-naive advanced/metastatic non—small- cell lung cancer (NSCLC). The effect, the authors from the KEYNOTE-042 study found, was agnostic of PD-L1 expression, meaning the monoclonal antibody was effective for tumors expressing PD-L1 at ≥50%, ≥20%, and ≥1%.

However, the secondary outcome of progression-free survival (PFS) was not met at data cut-off on February 26, 2018.

Previously, pembrolizumab monotherapy has shown significant improvement in OS over docetaxel as second-line treatment in metastatic NSCLC with PD-L1 tumor proportion score (TPS) ≥1%. Additionally, patients whose NSCLC had a PD-L1 TPS of ≥50% saw significant improvements in both PFS and OS with first-line pembrolizumab, compared with platinum-based chemotherapy (KEYNOTE-024).

Results from the KEYNOTE-189 study, published earlier this year, emphasized the advantage of combining chemotherapy with pembrolizumab: The researchers showed that the combination approach as first-line treatment in patients with metastatic NSCLC, who had no 

alterations, was significantly better than chemotherapy alone and was agnostic of PD-L1 expression.

“Our trial, KEYNOTE-042, is evaluating pembrolizumab monotherapy against platinum-based chemotherapy for metastatic NSCLC with low expression of PD-L1,” said lead author Gilberto Lopes, MD, MBA, Sylvester Comprehensive Cancer Center, University of Miami Health System. The trial was designed to develop a more effective and tolerable first-line treatment for metastatic NSCLC, he said.

Eligibility criteria included locally advanced or metastatic tumors with PD-L1 TPS ≥1%, without

 alterations. The ECOG status had to be 0 or 1; patients had to be free of untreated or unstable CNS metastases.

Treatment-eligible patients were randomized 1:1 to ≤35 cycles of pembroli- zumab 200 mg every 3 weeks or investigator’s choice of ≤6 cycles of paclitaxel + carboplatin or pemetrexed + carboplatin with optional pemetrexed maintenance (nonsquamous only). Primary end points were OS in patients with TPS≥50%, ≥20%, and ≥1%. Secondary end points were PFS and objective response rate for all 3 TPS, and safety in patients with TPS ≥1%.

At 12.8 months median follow-up, 13.7% of patients were still on pembrolizumab and 4.9% were receiving pemetrexed maintenance treatment.

In the TPS ≥50% subset, median OS at 24 months was 20 months (range, 15.4-24.9) in the pembrolizumab-treated patients (event rate: 44.7%) and 12.2 months (range, 10.4-14.2) in those treated with chemotherapy (event rate: 30.1%). Similarly, in the TPS ≥20% subset, median OS at 24 months was 17.7 months (range, 15.3-22.1) in the pembrolizumab-treated patients (event rate: 40.5%) and 13.0 months (range, 11.6-15.3) in those treated with chemotherapy (event rate: 29.6%). Among patients whose tumors expressed a low level of PD-L1 (TPS ≥1%), median OS at 24 months was 16.7 months (range, 13.9-19.7) in the pembrolizumab-treated arm (event rate: 39.3%) and 12.1 months (range, 11.3-13.3) in those treated with chemotherapy (event rate: 28.0%).

Lopes shared the PFS data in the TPS ≥20% cohort. Median PFS at 12 months was 6.2 months (range, 5.1-7.8) in the pembrolizumab-treated arm (event rate: 32.4%) and 6.6 months (range, 6.2-7.3) in those treated with chemotherapy (event rate: 28.8%).

Grade 3-5 drug-related adverse events (AEs) were less frequent with pembroli- zumab, Lopes said (17.8% vs 41.0% for chemotherapy). However, the rates of discontinuation (about 9.0%) and treatment-related deaths (about 2.0%) were similar between the 2 groups. Immune-related AEs (irAEs) are significant concerns that accompany the use of immune checkpoint inhibitors such as pembrolizumab.

 Lopes shared that about 27.8% of patients treated with pembrolizumab experienced irAEs, and 1 patient died as a result. Only 7% of patients in the chemotherapy arm had irAEs.

“KEYNOTE-042 is the first study with a primary end point of overall survival to demonstrate superiority of pembrolizumab over platinum-based chemotherapy in patients with previously untreated advanced/metastatic NSCLC without sensitizing 

alterations and a PD-L1 TPS ≥1%,” the authors concluded.

“Our data confirm and potentially extend the role of pembrolizumab monotherapy as a standard first-line treatment for patients with PD-L1—expressing tumors,” said Lopes. He shared that based on the advice of their external drug monitoring committee, the trial continues to evaluate PFS in this trial population.

Leena Gandhi, MD, currently the director of thoracic medical oncology and an associate professor of medicine at the New York University School of Medicine, who will soon be joining Eli Lilly and Company,

Comparing the performance of nivolumab, the other PD-1 inhibitor, with pembrolizumab, Gandhi questioned whether the crossover allowed in the CheckMate-026 study may have resulted in the failure of nivolumab as first-line treatment in advanced/metastatic NSCLC. “Overall, the studies are more similar than they are different,” she said. However, CheckMate-026 allowed 60.4% of patients in the chemotherapy arm to cross over to the nivolumab arm, whereas only 19.8% in KEYNOTE-042 who received chemotherapy were subsequently treated with pembrolizumab.

She identified several caveats with the KEYNOTE-042 results:

The benefit is driven by high PD-L1 expressors

PD-L1 expression has high clinical utility and should be used, but it could be complemented by following tumor mutation burden expression in the tumor samples

She advised researchers to analyze the tumor microenvironment

Lopes G, Wu Y, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first- line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: open-label, phase 3 KEYNOTE-042 study. 

Reck M, Rodriguez-Abreu D, Robinson AG, et al; KEYNOTE-24 Investigators. Pembrolizumab versus chemo- therapy for PD-L1-positive non-small-cell lung cancer. 

. 2016;375(19):1823-1833. doi: 10.1056/ NEJMoa1606774.

Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al; KEYNOTE-189 investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. 

. 2018;378(22):2078-2092. doi: 10.1056/NEJMoa1801005.

Davio K. Oncologists must weigh risks, benefits of immune checkpoint inhibitors. The American Journal of Managed Care® website. ajmc.com/conferences/nccn-2018/oncologists-must-weigh-risks-benefits-of-immune-check- point-inhibitors. Published March 26, 2018. Accessed June 4, 2018.

Leena Gandhi, MD, PhD, to lead Lilly oncology immuno-oncology medical development [news release]. Indianap- olis, IN: Eli Lilly and Company; April 30, 2018. prnewswire.com/news-releases/leena-gandhi-md-phd-to-lead-lil- ly-oncology-immuno-oncology-medical-development-300638547.html. Accessed June 4, 2018.

Phase 3 TAILORx Results Confirm Chemotherapy Unnecessary in 70% of Women With Early-Stage Breast Cancer

Trial Assigning Individualized Options for Treatment (Rx), or TAILORx, suc- cessfully confirmed the benefit of endocrine therapy (ET) alone in patients with early-stage breast cancer who have an Oncotype DX Breast Recurrence Score (RS) of 11 to 25.

The long-awaited results of the TAILORx study, the largest-ever breast cancer treatment trial, sponsored by the National Cancer Institute and led by the ECOG- ACRIN Cancer Research Group, were presented at the 2018 American Society of Clinical Oncology Annual Meeting by Joseph A. Sparano, MD, professor of medicine and obstetrics, gynecology, and women’s health at the Albert Einstein College of Medicine; associate chairman for clinical research in the Department of Oncology at Montefiore Medical Center; and associate director for clinical research at the Albert Einstein Cancer Center, all in New York City.

The Oncotype DX RS ranges from 0 to 100 and can predict chemotherapy benefit when the score is high, meaning higher than either 26. A score lower than 10 means the risk of distant recurrence is low, and the women will not benefit from chemotherapy. “The gray area has been the mid-range RS score of 11 to 25—this target population accounts for about 50% of women in the United States,” Sparano said.

The TAILORx trial was designed to help personalize treatment for women aged 18 to 75 years with hormone receptor—positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node (AN)-negative breast cancer whose tumors were 1.1 cm to 5.0 cm in size and who had a mid-range RS. The trial, which enrolled 10,273 women, aimed to clarify whether hormone therapy alone or together with chemotherapy is better for women with an RS of 11 to 25. The trial also was designed to confirm that a low RS of 0 to 10 is associated with a low rate of distant recurrence when patients receive endocrine therapy alone.

A majority (6711; 69%) of the 9719 eligible women had a midrange RS of 11 to 25 and were randomized to either the chemoendocrine treatment (CET) arm or the ET arm. Women with an RS of 10 or lower (1619; 17%) were in the ET arm and those with a RS of 26 or higher (1389; 14%) were in the CET arm. The primary endpoint was invasive disease-free survival (iDFS), and the trial was designed to show noninferiority for ET alone.

Key secondary end points included freedom from recurrence of breast cancer at a distant site, freedom from recurrence of breast cancer at a distant or local— regional site, and overall survival (OS).

At a median follow-up of 90 months (7.6 years), there were 836 iDFS events at final analysis. ET was noninferior to CET for iDFS (hazard ratio [HR], 1.08; 95% CI, 0.94-1.24; 

 = .26) in the intention-to-treat (ITT) population. ET was also noninferior for distant recurrence-free interval (DRFI; HR, 1.03; 

 = .80), recurrence-free interval (RFI; HR 1.12; 

Nine-year rates were similar for iDFS (83.3% vs 84.3%), DRFI (94.5% vs 95.0%), RFI (92.2% vs 92.9%), and OS (93.9% vs 93.8%) for the RS 11-to-25 arm. The overall recurrence rate was 5%. The study found 3% distant recurrence with ET alone in the RS 0-to-10 arm and 13% distant recurrence with CET in the RS 26-to-100 arm.

The study observed a potential chemotherapy benefit in younger women (≤50 years) with an RS of 16 to 25, while RS of 0 to 15 had good prognosis with endocrine therapy. “Chemotherapy should be used with caution in this [RS 11-to-25] subgroup with a shared decision-making process for deciding the treatment path,” Sparano concluded.

Sparano concluded that in women with hormone receptor—positive, HER2- negative, AN-negative breast cancer who had a RS of 11 to 25, adjuvant ET was not inferior to CET in the ITT analysis. However, recurrence was high in the RS 26-to-100 arm despite adjuvant CET.

“The results of our trial suggest that the 21-gene assay may identify up to 85% of women with early breast cancer who can be spared adjuvant chemotherapy, especially those who are older than 50 years of age and have a recurrence score of 25 or lower, as well as women 50 years of age or younger with a recurrence score of 15 or lower,” Sparano and colleagues wrote in the accompanying paper, published in the

Clinical findings as presented at the American Society of Clinical Oncology's Annual Meeting in June 2018.

ASCO Clinical Findings

Despite USPSTF Recommendations, Lung Screening Rates Low Among Heavy Smokers

conducted by researchers at the University of Louisville, Kentucky, has found that less than 2% of more than 7.5 million eligible smokers were screened for lung cancer in 2016 despite recommendations by the United States Preventive Services Task Force (USPSTF). These results were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

“This study makes a strong case that our country needs an effective public service campaign about encouraging lung cancer screening. Public service campaigns from the 1990s encouraged women to get mammograms, saving many lives in subsequent years. We need something similar to encourage current and former heavy smokers to get screened for lung cancer,” said ASCO President Bruce E. Johnson, MD, FASCO, in a press release that described the findings from the study.

A leading cause of cancer-related mortality, lung cancer is expected to be responsible for over 154,000 deaths in the United States in 2018, according to estimates by the American Cancer Society (ACS).

 This disease remains the most common cancer diagnosed in men and women.

In 2013, USPSTF rendered a B-grade recommendation

 for an annual lung cancer screening with low-dose computed tomography (LDCT) among adults aged 55 to 80 years who have a 30 pack-year history of smoking (defined as heavy smokers) and if they continue to smoke or did within the past 15 years (eligible smokers). The B recommendation means USPSTF expects a moderate to substantial net benefit from the LDCT screening service.

With their current study, the authors analyzed the impact of the USPSTF recommendation on screening rates using data from the Lung Cancer Screening Registry, which was acquired from the American College of Radiology in 2016. This registry spanned 1796 accredited radiographic screening sites. The data were compared with National Health Interview Survey estimates of eligible smokers who could be screened based on the USPSTF recommendations.

The geographic grid covered the Northeast, South, Midwest, and West, and the screening rate was derived by dividing the number of LDCT scans by the number of eligible smokers. Although the South had the most accredited screening sites (n = 663) and the highest number of eligible smokers, the screening rate in the region was the second lowest in the country (1.6%), with the West documenting the lowest screening rate (1%) and the fewest accredited screening sites (n = 232).

The overall national rate for screening among the potentially 7,612,965 eligible smokers was just under 2%: Only 141,260 individuals received LDCT screening.

Smoking cessation tools were offered to a significant portion (85%) of current smokers, and the authors report that the percentage of current and former smokers who were offered these tools was not influenced by the geographic location.

These results are not a surprise. A study4 commissioned by ACS and published in 

y in early 2017 found that lung cancer screening rates remained low, and unchanged, following the USPSTF recommendations.

Several questions remain unanswered, according to lead study author Danh Pham, MD, a medical oncologist at the James Graham Brown Cancer Center, University of Louisville, who presented the results during a press cast organized by ASCO. “Are physicians not referring enough or do patients resist screening?” Pham asked. He added that there is stigma associated with this screening test, which could also be responsible for the low rates of screening.

Further initiatives are needed, including awareness programs and mandating lung cancer screening as a national quality measure, the authors conclude in their abstract. “Effective screening can prevent nearly 12,000 premature annual lung cancer deaths,” Pham said during the press cast.

Pointing out that Medicare approved payment for LDCT screening only in 2015,5 Johnson said that the outcome being measured by this study has not yet reached a steady state. A long- term follow-up might provide a more realistic picture of where screening rates stand.

Pham D, Bhandari S, Oechsli M, Pinkston CM, Kloecker GH. Lung cancer screening rates: data from the lung cancer screening registry. 

. 2018;36(suppl; abstr 6504). abstracts.asco.org/214/AbstView_214_221571.html.

2018 estimates. ACS website. cancerstatisticscenter.cancer.org/?&_ ga=2.234243678.1588221490.1527713306-433943973.1527625724#!/. Accessed May 31, 2018.

Final recommendation statement: lung cancer: screening. USPSTF website. uspreventiveser- vicestaskforce.org/Page/Document/RecommendationStatementFinal/lung-cancer-screening. Published December 2013. Accessed May 31, 2018.

Jemal A, Fedewa SA. Lung cancer screening with low-dose computed tomography in the United States—2010 to 2015. 

. 2017;3(9):1278-1281. doi: 10.1001/jamaon- col.2016.6416.

National coverage determination (NCD) for screening for lung cancer with low dose com- puted tomography (LDCT) [press release]. Baltimore, MD: CMS; February 5, 2015. cms.gov/ Newsroom/MediaReleaseDatabase/Press-releases/2015-Press-releases-items/2015-02-05. html. Accessed May 31, 2018.

Clinical Trials: Sharing the Road With Real-World Evidence

In the era of real-world data and evidence, and their growing roles in oncology, panelists discussed collecting and using these data in combination with clinical trials to inform evidence-based care during a session at the 2018 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

Although clinical trials remain the gold standard for the context in which they were designed and developed—evaluating efficacy in tightly controlled and highly annotated samples&mdash;there are some drawbacks to using clinical trial data alone, explained Kathryn Reeder-Hayes, MD, MBA, MSc, assistant professor, University of North Carolina at Chapel Hill.

“In this context, assuming they meet their accrual goals, there [are] almost never too little data for the job in terms of the level of detail and the completeness of the data,” she said. She also noted that clinical trials are a familiar and comfortable form of evidence generation for multiple key stakeholders who are involved in the development of novel therapies for oncology.

However, clinical trials can also be prohibitively expensive and may not be the best fit for every question relevant to clinical practice, Reeder-Hayes warned. In particular, they are not optimally suited for questions of application of the innovational treatments being studied within the trial to broad and diverse populations. Neither are they well adapted to answer post hoc questions about differences in efficacy across subgroups or treatment application to populations outside the clinical trials, often because the sample is either too small, too homogenous, or both, for the data to be able to answer these questions.

“In those contexts, clinical trials may in fact waste time and resources, both in terms of our economic sources and our patients’ time,” said Reeder-Hayes. “In those contexts, real-world evidence, I would argue, may be less expensive and more appropriate for some questions as they relate to post hoc analyses and diffusion into broad populations.”

According to Reeder-Hayes, real-world evidence can be beneficial in several places:

After a randomized clinical trial is conducted, to test the dissemination of the findings and if they are being adopted, in which patients they’re being adopted, and which patient populations are being left behind.

Alongside randomized clinical trials, to extend findings to broader populations and answer secondary questions about differences among subgroups.

Before anticipating trials, to inform the important problems and questions, quantify effect sizes, and identify the right population.

She concluded by cautioning that big data studies require expertise in handling and analyzing observational data with its unique challenges related to potential bias and the need for complex data management strategies. Similar to clinical trials, these studies are best performed by experienced cross-disciplinary teams and are most useful when they answer the questions important to physicians and patients.

Sean Khozin, MD, MPH, director, Information Exchange and Data Transformation (INFORMED), followed Reeder- Hayes with an introduction to the FDA’s recently launched INFORMED program.

“Big data [have] many difference dimensions,” said Khozin. To explore and address these dimensions, the FDA launched the INFORMED program in April as an incubator for collaborative oncology science research. The program pairs engineers and data scientists with medical reviewers and regulatory scientists to conduct regulatory research using a variety of data inputs, including: clinical trials, electronic health records, biometric monitoring devices, and applications.

Remote Monitoring Can Reduce Radiation-Related Symptoms in Head and Neck Cancer

From these inputs, results come in the form of publications, abstracts, and, more recently, codes and algorithms that can be incorporated into decision support tools, explained Khozin. Outputs also include policy positions and guidance documents that can disseminate findings to the community and inform development programs, he added.

Use of the mobile and sensor technology CYCORE (CYberin- frastructure for COmparative Effectiveness Research) to remotely monitor symptoms in patients with head and neck cancer (HNC) undergoing radiation therapy found these patients had fewer symptoms overall and specific to HNC.

 presented at the 2018 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, was included in a press cast that was broadcast ahead of the meeting.

According to the National Cancer Institute, over 51,500 individuals

will be get an HNC diagnosis in 2018, accounting for over 3% of new cancer diagnoses for the year. Although the 5-year survival rate of this cancer hovers close to 65%, a little over 10,000 patients are estimated to die from the disease this year in the United States. HNC patients have high risk of symptom burden and risk of dehydration.

Chemotherapy, surgery, and radiation therapy are the forms of treatment available for patients with HNC, but the treatment plan is determined based on disease stage, potential side effects, and the patient’s overall health and preferences. Patients who receive radiation therapy may experience significant treatment-related burden,

 including pain, difficulty swallowing, swelling and scarring at the site of treatment, and loss of appetite, all of which can lead to dehydration. Other side effects include dry mouth, bone pain, nausea, fatigue, mouth sores, and hearing loss.

Researchers from 4 institutions, who designed and implemented the current trial, used CYCORE to compare remote patient monitoring with usual patient care among 357 patients. A majority of the patients were male, and there were 169 patients in the CYCORE arm and 188 in the usual care arm of weekly doctor visits. Patients in the CYCORE arm were provided with blood pressure cuffs and weight scales that were Bluetooth-enabled and given mobile tablets with proprietary Wi-Fi. Sensor readouts were transmitted to firewall-protected computers through a secure mobile app to ensure data protection.

The real-time readouts were reviewed on a daily basis by physicians, which allowed for an early intervention if needed. Patients in both groups had a weekly in-person visit with their physician.

Patients filled out the 28-item MD Anderson Symptom Inventory (MDASI) survey4 prior to initiation of radiation treatment, at the end of therapy, and 6 to 8 weeks after radiation ended. A scale of 0 to 10 was used to rate symptom severity, with lower scores indicating better outcomes.

The study found that while there was no difference in self- reported health severity scores between the 2 groups at the start of the trial, MDASI scores of the CYCORE group were lower for severity of general (2.92 vs. 3.4; 

 = .003) and HNC-specific symptoms (4.21 vs 4.83; 

 = .009) at the completion of the radiation treatment. Similarly, MDASI scores were lower for the CYCORE group at 6 to 8 weeks after completing radiation, for general (1.69 vs 1.96; 

 = .003) and HNC-specific symptoms (1.78 vs. 2.11; 

“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,” said lead study author Susan K. Peterson, PhD, MPH, professor, Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, in a press release. “This study was done during a rather intense period in the patients’ care for head and neck cancer. The system helped their physicians to provide valuable support that ultimately resulted in lower symptom severity.”

An important observation was the high rate of adherence in a majority of patients, despite the intensity of treatment. “Using mobile tech for remote monitoring of patients during critical periods of outpatient treatment can provide timely info for clinical decision making and can improve [quality of life] and health outcomes,” the authors concluded.

Peterson SK, Garden AS, Shinn EH, et al. A study exploring the use of mobile and sensor technology to monitor symptoms in patients with head and neck cancer receiving radiation therapy. 

. 2018;36(suppl; 6063 abstr). abstracts.asco.org/214/Abst- View_214_230683.html.

Key statistics for oral cavity and oropharyngeal cancers. American Cancer Society website. cancer.org/cancer/oral-cavity-and-oropharyngeal-cancer/about/key-statistics.html. Published February 15, 2018. Updated March 9, 2018. Accessed May 30, 2018.

Head and neck cancer: treatment options. Cancer.net website. cancer.net/cancer-types/ head-and-neck-cancer/treatment-options. Published August 2017. Accessed May 30, 2018.

MDASI head and neck cancer module. MD Anderson website. mdanderson.org/research/ departments-labs-institutes/departments-divisions/symptom-research/symptom-as- sessment-tools/md-anderson-symptom-inventory-head-and-neck-cancer-module.html. Accessed May 30, 2018.

Discussing the Cost Burden of Cancer With Patients

Patients with cancer often have medical bills and other health costs significantly higher than those of others. Now, with cancer drugs becoming increasingly effective and more tolerable for patients, patients take these drugs for longer periods of time, leading to increased financial burden, said oncologist and health services researcher Ryan Nipp, MD, MPH, during a session at the 2018 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois. Nipp is with Massachusetts General Hospital Cancer Center in Boston.

In addition to out-of-pocket costs, such as co-payments, deductibles, and prescriptions, patients with cancer often experi- ence issues indirectly related to finances during cancer treatment, he said, including:

Employment issues such as missing work, being on disability, or “job lock,” when patients feel they cannot change jobs because it would interrupt health coverage.

Lifestyle factors including interruptions to their children’s education, or being unable to pay the mortgage or basic living expenses.

Concurrent issues such as psychological distress, fear of the unknown, and symptom burden.

Patients with cancer experience financial burdens related to the disease and its treatment across all insurance types at higher rates than those with other chronic conditions and those with no chronic conditions, explained Nipp; 43% of privately insured patients with cancer spend more than 20% of their income on health-related costs, compared with 29.8% of such patients with another chronic condition and 16.4% of those with no chronic condition. For those with public insurance, 24% of patients with cancer spend more than 20% of their income on health-related spending, compared with 18.7% and 5.8% of the other groups, respectively.

“Increasingly, efforts are needed to foster appropriate patient—clinician communication about the cost of cancer care,” said Nipp. Such “discussions...have the potential to improve care delivery and outcomes for patients by fostering informed decision making.”

However, numerous barriers face both clinicians and patients, he explained. For clinicians, barriers include lack of knowledge about costs incurred by patients, potentially time-consuming discussions, concerns that providing information about cost may encourage patients to forgo care, and concerns that cost discussions may jeopardize the patient—clinician relationship.

Care strategies updates from the American Society of Clinical Oncology's Annual Meeting, held June 2018.

Care Strategies

Ambassador Nancy G. Brinker, founder and chair of Global Strategy, Susan G. Komen

When you started Susan G. Komen, there was a lot of stigma surrounding the subject of breast cancer. How did you bring the conversation about breast cancer into the open?

Well, we really brought it out into the open because it was there, it was growing. People just didn’t have the place to talk about it or share their feelings or share their insights or survival or their treatment—or their lack of survival. It was really waiting to happen. Because I had lost my only sister to the disease in 1980 and she asked me, I promised her that I would help cure breast cancer.

So, it’s been a long ride, a long time. It’s been almost 40 years of my life—she was diagnosed in 1978&mdash;and I realized that we had to do something, and it was going to require a movement. It wasn’t just going to be a one-[time] fundraiser, it was a movement. And of course, this pre-dated computers and cellphones and fax machines and everything else. We really only had telephones and each other to work with. 

So, we named it Susan G. Komen in her honor, her memory, and set about working for many, many years. We’ve managed to bring up the awareness, the sharing, and we’ve created a large community—a worldwide community&mdash;focused on breast cancer.

What do you see as the future of the Susan G. Komen Foundation?

What I think is that the organization, every organization goes through major changes and rebuilding and new ideas and innovation. It’s time for major innovation.

We have such strength in our affiliate communities, who are really people on the ground that have learned so much. It’s not so much what we do, it’s how we do it that’s going to be very important.

People are very sensitive to high overheads, they’re very sensitive to any- thing spent. They want to see money that they give go directly to a mission. So we’re going to try very hard to make sure that we have collaborations with other people already doing the same thing, that we do things in a way—as we’ve always tried to do&mdash;as cost-effective as possible. Events become very ex- pensive to do, so we have to figure out other ways [to use] technology to raise money and make sure that we connect with people.

John Schorge, MD, associate editor of The Green Journal and gynecologic oncologist at Tufts Medical Center

[We also need to] get people of wealth in the country to understand that it’s as important to fund a program as it is a building. In fact, sometimes the program goes farther to train people, to bring people in the system. So those are the sorts of things we’ll work on.

What has your research shown about different methods to prevent ovarian cancer?

[My] presentation [was] about ovary cancer and the current updates. It is the case that ovary cancer happens in about 1 [in] 70 women in their lifetime. [There are] people that are at higher genetic risk for that, but really, it’s been a disappointing number of decades trying to identify a screening test. So part of the presentation is just kind of presenting the data [that are] out there, showing that it’s not all that helpful.

There are some methods of preventing ovarian cancer, such as removal of the ovary. It’s [known as] prophylactic surgery, [and it’s meant] to reduce the risk. However, that comes with menopausal, early menopause, and other health consequences. What has been more recently shown is that many of these “ovarian cancers” actually start in the tube, and the tube has no function other than allowing pregnancy.

So, what has tilted in the last couple of years—and the ACOG [American College of Obstetrics and Gynecology] practice bulletins sort of magnify&mdash;[is] the recommendation to remove the tube at the time of GYN surgery or instead of tubal ligation. We think that that is one of the more effective ways, and easy ways, of decreasing ovarian cancer in the United States.

What were the findings of your study that investigated the delivery of neoadjuvant chemotherapy to women with advanced ovarian cancer?

One of the conundrums, and controversies, in the field is people [who] present with ovarian cancer. Two-thirds of the time it’s fairly advanced. Whether to start with surgery first or chemotherapy first has been the dilemma. Historically, people have started with surgery first, and yet over the last decade or so, there’s been a lot more evidence that starting with chemotherapy— such as neoadjuvant chemotherapy, which means chemo first&mdash;seems to work out just as well in the long run in many cases.

Part of our work was looking at that trend and then determining that [to be] an interval operation, which means halfway through the chemotherapy. If you’re able to do a minimally invasive operation, like a standard laparoscopy, people have similar outcomes to open surgery and a lot fewer side effects and a lot less complication risk.

In your retrospective analysis, how were palliative care services utilized in ovarian cancer and was the utilization in line with national guidelines?

Yes, we did look at palliative care practices specifically for ovarian cancer. It is a relevant topic in that field in that even though most ovarian cancer patients will go into remission, 80% to 90% will relapse. And when a woman has relapsed, it is at some point a palliative care discussion. 

AJMC®TV interviews let you catch up on what’s new and important about changes in healthcare, with insights from key decision makers&mdash;from the clinician, to the health plan leader, to the regulator. When every minute in your day matters, AJMC®TV interviews keep you informed. Access the video clips at ajmc.com/interviews.
 

July 2018

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Care Strategies

AJMCtv® Interviews, July 2018

Prevention and Managed Care Updates

Clinical Updates

CAR T-Cell Therapy Update