FDA apporval on tumor agnostic treatment 

Key Highlights

Our experts weigh in on some of the important topics and trends they anticipate to see this year at ASCO 2018 in Chicago.
In the final o f a series of blogs, Dr. Luis Mendoza and Dr. Forrest Anthony, both members of IQVIA's Therapeutic Science and Strategy Unit, discuss why immune checkpoint inhibitors are transforming cancer care.

Every year, oncology experts from across the globe come together at the American Society of Clinical Oncology’s (ASCO) annual meeting to share their latest developments in oncology research and discuss the next generation of therapeutic innovation. Over the past several years, many of these conversations and sessions have focused on advances in immuno-oncology – and immune checkpoint inhibitors (ICIs).
Immunotherapies, including immune checkpoint inhibitors are transforming cancer care. Instead of stimulating the immune system directly, ICIs block the brakes that tumors apply to the immune system so that immune system cells can continue to attack and kill cancer cells.  This medical innovation has delivered unprecedented value in the successful treatment of cancer patients, even where other treatments have failed. In its 2018 annual report, ASCO estimates that immune checkpoint inhibitors would “save 250,000 years of life if all US patients with advanced lung cancer for whom ICIs are currently indicated receive the treatment.” It also states that one in four newly diagnosed cancer patients, and one in 10 patients with previously treated disease, may live well beyond five years after treatment initiation thanks to ICIs.
The U.S. Food and Drug Administration (FDA) has already approved several immune checkpoint inhibitors to address nine different cancers, with several more in development. Among the most notable are two accelerated approvals granted last years for ICIs addressing microsatellite instability-high (MSI-H) colorectal and non-colorectal tumors.  Pembrolizumab was approved for the treatment of adult and children with unresectable or metastatic MSI-high or DNA mismatch repair deficient (dMMR) solid tumors; and nivolumab was approved for the treatment of patients 12 and older with dMMR and MSI-H metastatic colorectal cancer that has progressed following treatment.
The success of these two drugs is significant because they are the first ICIs approved on the basis of the genetic make-up of the tumor, rather than the specific tumor type or location. In other words, these indications are tumor-agnostic (also termed tissue-agnostic or site-agnostic) These advances in ICIs to treat MSI-H tumors are particularly notable because these tumors can have thousands of mutations and represent a significant percentage (10-30%) across a significant fraction of tumors. One of the studies for pembrolizumab included patients with 12 different tumor types using the same treatment, and 21% of those patients went into complete remission.
To date, pembrolizumab and nivolumab are the only two drugs to receive approvals based on a tumor’s biomarker status without regard to the tumor’s original tissue type or location. While these drugs are groundbreaking on their own, they also represent an exciting shift in the way oncology treatments can be developed, tested, and used to create opportunities for a single treatment to address multiple kinds of cancer. These approvals underscore the exciting advances being made in the arena of ICIs, and herald a new generation of oncology treatment based on tumor signature rather than tumor type. 

Let’s Connect at ASCO

We recently coauthored a white paper for IQVIA clients and clinical staff on how ICI tumor agnostic treatment approvals represent a promising new direction for oncology care. We and IQVIA experts are also looking forward to the ASCO meeting June 1-5 in Chicago, to discuss these and other oncology trends with peers from across the industry and to learn about innovations in oncology.
We know several speakers at the event will focus on trends in ICIs, including Dr. Gavin Dunn from the Washington University School of Medicine, who is giving an update on Checkpoint Inhibitors and Combinatorial Approach to Targeted Immunotherapies; and Dr. Jennifer Ann Wargo, from the University of Texas MD Anderson Cancer Center who will present on Novel Checkpoint/Targeted Therapy Combinations. We will also hear about some of the risks related to ICIs, including a presentation on Immune-Checkpoint Toxicity from Dr. Marc Ernstoff, of the Cleveland Clinic; and an education session on Primary and Acquired Resistance to ICIs.
The opportunity to hear these kinds of presentations and to talk with experts who’ve dedicated their careers to advancing oncology care is why ASCO is one of the most important events of the year. Researchers spend most of their time with their heads down, pursuing new treatment innovations, but oncology innovations don’t happen in a vacuum. By taking the time to come together at ASCO and other industry events we can share our successes, find new collaborations, and help drive innovation on behalf of all patients while ensuring the safety and efficacy of the trials we lead and the treatments that come to market. We look forward to seeing you there


More about our contributors

Forrest H. Anthony, MD, PhD

Forrest H. Anthony, MD, PhD, is Senior Director IQVIA Oncology Center of Excellence, North America. Dr. Anthony has more than 25 years’ experience in the biopharmaceutical industry. He works on customer drug development projects, and trains global staff to anticipate scientific innovations (e.g., immuno-oncology, Adoptive Cell Therapy, CAR-T therapies, oncolytic viruses).

 Luis Mendoza, MD, PhD

Luis Mendoza, MD, PhD, is Senior Medical Director of IQVIA’s Oncology-Hematology Therapeutic Science & Strategy Unit. Dr Mendoza joined IQVIA in 2015 after 20 years in the oncology medical practice combined with 12 years of experience in clinical development of different oncology compounds. Besides his clinical research experience with different anticancer monoclonal antibodies, immunomodulatory drugs, bi-specific monoclonal antibodies, oncolytic virus vaccines, cellular therapies etc and he has been focused leading clinical trials for novel checkpoint inhibitors and novel immunotherapies. Dr Mendoza is editorial board member of oncology-hematology journals and author of dozens of publications in peer-reviewed journals.

https://www.iqvia.com/blogs/2018/05/tumor-agnostic-immune-checkpoint-inhibitors

Men whose brothers have aggressive prostate cancer at increased riskal. J Clin Oncol. 2018;doi:10.1200/JCO.2017.76.6907.

Men whose brothers had non-low-risk prostate cancer faced a significantly increased risk for developing an aggressive form of the malignancy, according to results of a study conducted in Sweden.

Men with one or two first-degree relatives with prostate cancer have a two- to fivefold increased risk [for] being diagnosed with prostate cancer compared with men with no family history of prostate cancer, and the risk is also increased among men with second- and third-degree relatives with prostate cancer. Previous twin studies have assessed the concordance of a prostate cancer diagnosis but not the concordance of the type of prostate cancer. “If there is prognostic concordance within families, then knowledge of tumor characteristics and disease development among relatives may be helpful when counseling men with suspected or newly diagnosed prostate cancer.”

The researchers used the Swedish Prostate Cancer Database to identify 4,262 sets of brothers who both were diagnosed with prostate cancer. Jansson and colleagues categorized cancers as either low risk (Gleason score, 6 or lower; clinical stage, T1 to T2; PSA, 10 ng/mL or less) or non-low risk. They used logistic regression to calculate odds ratios for concordance of non-low-risk cancer among monozygotic twins, dizygotic twins, full brothers and half brothers.

After adjusting for year of diagnosis and age, the highest concordance of non-low-risk disease occurred among monozygotic twins (OR = 3.82; 95% CI, 0.99-16.72). Full brothers also had a significant concordance (OR = 1.21; 95% CI, 1.04-1.39). These results persisted when researchers restricted analysis to brothers diagnosed within 4 years of each other.

Monozygotic twins had a significantly shorter median time between diagnoses than other groups (1.1 years) than full brothers (3.2 years; P < .001), dizygotic twins (2.8 years; P < .014), paternal half brothers (4.1 years; P < .001) and maternal half brothers (3 years; P < .003). The results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk for] developing an aggressive prostate cancer himself.

https://www.healio.com/hematology-oncology/prostate-cancer/news/in-the-journals/%7B6ae1a9af-356a-4699-ab69-44d7ae3c119f%7D/men-whose-brothers-have-aggressive-prostate-cancer-at-increased-risk

Low-fat diet improves breast cancer survival

Chlebowski RT, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.1212.

Women diagnosed  with breast cancer while eating a low-fat diet had better OS than those who ate a usual diet, according to a secondary analysis of a randomized trial. This reduction in mortality appeared partly due to increased survival from other health issues.

Researchers of the randomized Women’s Health Initiative study assessed the impact of a low-fat diet on the prevention of breast cancer. During follow-up, researchers observed significantly fewer deaths among women with breast cancer in the dietary intervention group (HR = 0.82; 95% CI, 0.7-0.96).The observed favorable effects on deaths after breast cancer could have resulted from prediagnosis dietary influences on cancer characteristics.

The trial was conducted at 40 centers across the U.S. from 1993 through 1998 — which included 48,835 postmenopausal women with no breast cancer history and a dietary fat intake of more than 32%.

The dietary intervention (n = 19,541; 40%) reduced participants’ fat intake to 20%, as well as increased consumption of fruits, vegetables and grains. Women diagnosed with breast cancer during the study continued the dietary intervention.

Post hoc analyses for OS for breast cancer diagnosed during the intervention, which ran for a median of 8.5 years, served as the main outcome. Analyses occurred after a median of 11.5 years following diagnosis.

A total of 1,764 women were diagnosed with breast cancer during the intervention period. Median age at screening was 62.7 years, and median age at time of diagnosis was 67.6 years.

A total of 516 women died.

Breast cancer OS in the dietary intervention group significantly improved compared with the usual diet group (10-year OS, 82% vs. 78%; HR = 0.78; 95% CI, 0.62-0.94).

Sixty-eight women in the dietary group died of breast cancer compared with 120 in the usual diet group (HR = 0.86; 95% CI, 0.64-1.17).

Fewer women in the dietary group died of other cancers (36 vs. 65; HR = 0.76; 95% CI, 0.5-1.17), or of cardiovascular disease (27 vs. 64; HR = 0.62; 95% CI, 0.39-0.99).

The researchers acknowledged that the study was limited by a “modest” increase in fruit, vegetable and grain intake, as well as incomplete information on patients’ breast cancer therapies.

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“In women who received a diagnosis of breast cancer during the dietary intervention period, those in the dietary group had increased breast cancer OS compared with those in the usual-diet comparison group,” the researchers wrote. “This increase is likely due, in part, to better survival from several causes of death.”

https://www.healio.com/hematology-oncology/breast-cancer/news/in-the-journals/%7B9be1c3f1-25ad-4f30-b1d7-4df1a978f34b%7D/low-fat-diet-improves-breast-cancer-survival

 

Breath analysis test shows strong accuracy for detecting esophagogastric cancer

arkar SR, et al. JAMA Oncol. 2018;doi:10.1001/jamaoncol.2018.0991The breath test showed good sensitivity and specificity in detecting early-stage esophagogastric cancer, according to researchers in the U.K.

“Current U.K. referral guidelines for suspected esophagogastric cancers focus on alarm symptoms such as dysphagia and odynophagia, despite these symptoms having poor sensitivity and specificity for esophagogastric cancer and often only occur in advanced disease translating into a poor outcome and overall survival.“

Volatile organic compounds (VOCs) emitted from the human body have been of interest to researchers for several decades, with associations previously suggested between specific volatile organic compounds and breath and lung, bladder and breast cancers. Researchers collected breath samples from 335 patients at three London hospitals (n = 172 in control group, n = 163 with esophagogastric cancer). The researchers then performed selected ion flow tube mass spectrometry analysis on the samples. Researchers sampled the air in hospital rooms, trained researchers in breath sampling, calibrated instruments regularly and conducted unambiguous VOC identification to ensure the quality of the breath samples. Researchers used a previously generated 5-VOCs model to determine the risk for cancer based on the air samples compared with proven diagnoses.

The group with proven cancer was older than those in the control group (median age, 68 years vs. 55 years) and had a larger proportion of men (82.2% vs. 47.4%).

Most patients in the diagnosed group had a tumor stage of T3 or T4 (n = 123; 69%), and most had nodal metastasis (n = 106; 65%).

The breath analysis test demonstrated a sensitivity of 80%, and a specificity of 81%.

“The next stage is a large-scale diagnostic accuracy study among the primary care population where the test is intended to be employed”

https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/in-the-journals/%7B33e382f0-2f85-43cc-aa68-b26982794c4a%7D/breath-analysis-test-shows-strong-accuracy-for-detecting-esophagogastric-cancer

Sodium thiosulfate lowers risk for hearing loss among children with hepatoblastoma

Great news to reduce the ototoxicity of the chemotherapy

Children with standard-risk hepatoblastoma who received sodium thiosulfate 6 hours after cisplatin chemotherapy had a 48% lower incidence of cisplatin-induced hearing loss, according to phase 3 results from the SIOPEL 6 clinical trial published in The New England Journal of Medicine.

Cisplatin chemotherapy and surgery are standard treatments for children with standard-risk hepatoblastoma. However, hearing loss – a side effect of cisplatin chemotherapy - can affect learning, development and quality of life among young children.

Previous studies have shown that sodium thiosulfate may have an otoprotective effect, with maximum efficacy when administered 4 to 8 hours after cisplatin therapy.

Researchers randomly assigned children aged 1 month to 18 years to receive 80 mg/m² cisplatin alone over 6 hours (n = 52; median age, 13.4 months) or cisplatin plus 20 g/m² IV sodium thiosulfate (n = 57; median age, 12.8 months) over a 15-minute period, 6 hours after discontinuing cisplatin in four preoperative and two postoperative courses.

Investigators used the Brock grade scale to measure hearing loss.

Absolute hearing threshold at a minimum age of 3.5 years measured by pure-tone audiometry served as the primary endpoint. Secondary endpoints included OS and EFS at 3 years.

The intention-to-treat population comprised 109 children, of whom 101 could be evaluated for the primary endpoint.

Hearing loss of grade 1 or higher occurred among 18 of 55 children (33%; 95% CI, 21-47) evaluated in the cisplatin-sodium thiosulfate group compared with 29 of 46 children (63%; 95% CI, 48-77) in the cisplatin alone group.

The RR of any hearing loss with sodium thiosulfate was 0.52 (95% CI, 0.33-0.81), which indicated a 48% lower risk than with cisplatin alone.

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At median 52 months of follow-up, 3-year OS was 98% (95% CI, 88-100) in the cisplatin-sodium thiosulfate group and 92% (95% CI, 81-97) in the cisplatin-alone group.

https://www.healio.com/hematology-oncology/pediatric-oncology/news/in-the-journals/%7B632aedbb-a705-4b71-8790-7314b1677782%7D/sodium-thiosulfate-lowers-risk-for-hearing-loss-among-children-with-hepatoblastoma.

 

Cancer increases risk for subsequent diabetes

Cancer increased patients’ risk for subsequently developing diabetes, according to results of a cohort study conducted in South Korea.

The researchers performed a cohort study of 524,089 Korean individuals aged 20 to 70 years. The cohort had no history of cancer or diabetes, and they underwent observation for up to 10 years from 2003 to 2013.

Incident cancer served as an exposure, and the main outcome was incident type 2 diabetes following cancer as determined by insurance claim codes.

Over a median 7 years of follow-up for 494,189 individuals (mean age, 41.8 years; 50% women), 15,130 patients developed cancer and 26,610 developed diabetes.

Of those who developed diabetes, 834 patients had previously been diagnosed with cancer (incident rate, 17.4 per 1,000 person-years).

Cancer appeared associated with an increased risk for subsequent diabetes after adjustment for age, sex, precancer diabetes risk factors, metabolic factors and comorbidities (HR = 1.35; 95% CI, 1.26-1.45).

Diabetes risk appeared highest the first 2 years following cancer diagnosis. However, it remained elevated throughout the follow-up period.

Pancreatic cancer had the strongest association with diabetes (HR = 5.15; 95% CI, 3.32-7.99), followed by kidney (HR = 2.06; 95% CI, 1.34-3.16), liver (HR = 1.95; 95% CI, 1.5-2.54), gall bladder (HR = 1.79; 95% CI, 1.08-2.98), lung (HR = 1.74; 95% CI, 1.34-2.24), blood (HR = 1.61; 95% CI, 1.07-2.43), breast (HR = 1.6; 95% CI, 1.27-2.01), stomach (HR = 1.35; 95% CI, 1.16-1.58) and thyroid (HR = 1.33; 95% CI, 1.12-1.59) cancers.

The study was limited by a lack of information on cancer stage, as well as by little information on treatment and outcomes derived from insurance data.

https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/in-the-journals/%7B8212889b-9fc4-4366-8e8e-13be50cd9182%7D/cancer-increases-risk-for-subsequent-diabetes