The OBR Blog

May 29, 2020 - 01:05 am comments0 Comments

Several late-breaking abstracts dropped ahead of this weekend’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. The studies cover new data from two cancer registries (CCC19 and TERAVOLT) assessing the impact of COVID-19 on patients with cancer, and results from the TROPHIMMUN trial and INFORM registry.

CCC19

Patients with cancer and COVID-19 had a heightened risk of dying if they had active disease, according to the first analysis of an ongoing COVID-19 and Cancer Consortium (CCC19) registry (Abstract LBA110).

Among 928 patients included in the analysis, 121 (13%) died at a median follow-up of 21 days. A multivariable logistic regression model that was partially adjusted revealed several factors associated with increased risk of death: older age, male sex, former smoking, high number of comorbidities , ECOG performance status great than 2, and active cancer.

For those with active cancer, having a stable or responsive disease was associated with a nearly two-fold increased risk (partially adjusted odds ratio [pAOR]=1.93; 95% CI, 1.06-3.5) and disease progression a nearly four-fold increased risk (pAOR=3.79; 95% CI, 1.78-8.08).

Receipt of azithromycin and hydroxychloroquine together was also associated with an increased risk of death. However, study presenter Jeremy Warner, MD, associate professor of medicine and biomedical informatics at Vanderbilt University Medical Center, cautioned that this finding is of “uncertain validity” due to a “high risk of residual confounding.”

“For example,” he said, “patients receiving this combination were more likely to have severe disease or more likely to be hospitalized.”

TERAVOLT

Prior receipt of chemotherapy, but not immunotherapy or tyrosine kinase inhibitors, was associated with increased risk of death for patients with thoracic malignancies and COVID-19, according to an updated analysis of the ongoing Thoracic cancERs international coVid 19 cOLlaboraTion (TERAVOLT) registry (Abstract LBA111).

Among 400 patients included in the analysis, 141 (35%) died at a median follow-up of 33 days. Most deaths (79.4%) were attributed to only COVID-19, while 10.6% were attributed to cancer. Most patients were hospitalized (78.3%).

A multivariate analysis revealed that age, ECOG performance status, use of steroids of greater than 10 mg per day, and prior receipt of chemotherapy were associated with increased risk of death. None of the therapies given to treat COVID-19 were significantly associated with outcomes.

TROPHIMMUN

Avelumab appeared to benefit patients with gestational trophoblastic tumors (GTT) resistant to monochemotherapy, according to data from cohort A of the TROPHIMMUN phase 2 trial (abstract LBA6008).

GTT are characterized by high levels of human chorionic gonadotropin (hCG), and among the 15 patients from cohort A who received avelumab after developing resistance to monochemotherapy, 7 achieved normal levels of hCG during treatment and one was achieved after.

No patients had disease relapse, which study presenter Benoit You, MD, PhD, Institut de Cancérologie des Hospices Civils de Lyon, interpreted as meaning these patients were “potentially cured.”

One woman who achieved normal levels of hCG went on to have a normal pregnancy and healthy baby, which is the first report of a patient achieving a normal pregnancy after treatment with immunotherapy.

No patients required dose reductions or delays, and common adverse events were fatigue (33%), nausea and vomiting (33%), infusion-related reactions (27%), thyroid disorder (20%), dry eyes (20%), and diarrhea (20%).

A phase 1/2 trial called TROPHAMET is ongoing to evaluate avelumab with methotrexate as a first-line treatment for patients with GTT.

INFORM

A 7-step treatment algorithm successfully identified molecular targets in children with relapsed cancers and matched them to targeted therapies; a subset of these patients even had a clinical benefit (abstract LBA10503).

Part of the INFORM registry, 526 children were evaluated with the treatment algorithm and 149 were matched to targeted drugs, of whom 20 had a very-high priority molecular target. Extremely high priority targets were primarily ALK, BRAF, and NRAS mutations and MET and NTRK-fusions.

The algorithm also identified 40 children with potential cancer predisposition syndrome, 17 of which were unaware of having the syndrome.

The subset of children with a very-high priority target had a significantly longer progression-free survival compared with the rest of the children (204.5 days vs 114 days; P=0.0093).

A set of biomarker-driven pediatric phase 1/2 trials, known as INFORM2, are underway.

By Christina Bennett, MS

May 13, 2020 - 09:05 pm comments0 Comments

At a pre-meeting press conference, ASCO gave reporters a peek at some of the important presentations at the upcoming ASCO20 Virtual Scientific Program.  The topics covered include smoking and lung cancer, maintenance therapy for ovarian cancer, the value of geriatric assessment, changes wrought by the Affordable Care Act, and videoconferencing for caregivers.

Smoking and Lung Cancer

A large pooled analysis of 17 studies with a total of almost 35,000 patients enrolled in the International Lung Cancer Consortium (ILLCCO) showed that quitting smoking at any time prior to diagnosis improved lung cancer-specific survival and overall survival [Abstract 1512].

The risk of overall death was reduced by 12% for people who quit less than 2 years before their diagnosis, 17% if the interval was 2-5 years, and 20% if it had been more than 5 years since stopping smoking (all comparisons were with current smokers). However for lung cancer-specific survival, the benefit was significant only for those who quit more than 5 years prior to diagnosis compared with current smokers at the time of diagnosis.

“This research shows that if you are a current smoker and you quit, no matter when you quit you will be more likely to survive after being diagnosed with lung cancer compared to someone who continues smoking,” said lead author Aline Fusco Fares, MD, clinical research fellow at Princess Margaret Cancer center in Toronto. “The study’s message is simple: quit smoking now.”

“The improvements in survival seen even with quitting a short time before lung cancer diagnosis show that it’s never too late to stop smoking,” said ASCO President Howard A. Burris, III, MD.

Maintenance Olaparib in Ovarian Cancer

The final overall survival analysis of the double-blind, randomized, multicenter SOLO2 trial showed that maintenance therapy with olaparib provided an unprecedented improvement of 12.9 months of median overall survival versus placebo in patients with platinum-sensitive recurrent ovarian cancer and a BRCA mutation [Abstract 6002].

At 5 years, 28.3% of patients in the olaparib arm were alive and did not need subsequent treatment versus 12.8% of patients in the placebo arm. At 5 years, 42.1% of olaparib patients were alive versus 33.2% of placebo patients.

Patients who received olaparib in the time between response and disease progression had a 26% reduced risk of death. In addition, 38.4% of the placebo arm crossed over to treatment with olaparib.

“This is the first study with olaparib tablets … to provide long-term follow-up and final overall survival data in patients with platinum-sensitive relapsed ovarian cancer,” said lead author Andreas Poveda, MD, Initia Oncology Hospital Quironsalud, Valencia, Spain.

“A median overall survival improvement of nearly 13 months is impressive in ovarian cancer and brings a substantial benefit to our patients. With the addition of overall survival data, this study helps usher in a new era of personalized medicine for women with this difficult-to-treat cancer,” Dr.Poveda added.

Geriatric Assessment and Management

Integrating geriatric assessment (GA) and geriatrician-led collaborative care for patients over age 70 slated for chemotherapy, targeted therapy, or immunotherapy improved outcomes for both patients and the healthcare system [Abstract 12011].

The INTEGERATE prospective randomized study of 154 patients showed that comprehensive GA and geriatrician-led management of issues identified in the GA improved patients’ quality of life, reduced emergency room visits, reduced in-hospital stays, and enabled more patients to stay on treatment compared with usual care.

“The comprehensive GA is a powerful tool, because it helps optimize care for older cancer patients. Older people receiving systemic anti-cancer therapy should receive comprehensive GA management to optimize their clinical care and health outcomes. This is one of  the first randomized trials to show benefits to both the patient and the healthcare system,” said lead author Wee-Kheng Soo, MD, geriatrician and medical oncologist at Eastern Health, Melbourne, Australia.

ACA and Expansion of Medicaid

The first study to directly measure cancer survival after implementation of expansion of Medicaid under the Affordable Care Act (ACA) found greater decreases in cancer mortality rates in states that adopted Medicaid expansion than in states that did not: 29% from 1999-2017 versus 25%, respectively [Abstract 2003].

The additional mortality benefit for states that adopted Medicaid expansion amounted to an estimated 785 fewer cancer deaths in 2017 alone.

Looking at subpopulations, it was somewhat surprising to find that although African Americans patients had large mortality gains during the study period, no additional reduction in mortality was observed for them in states with Medicaid expansion, while Hispanic patients had a greater magnitude of improvement in mortality in states that adopted Medicaid expansion. The authors said that it is not clear why African Americans failed to experience the same magnitude of benefit in these states and that further study is needed.

“This is the first study to show the benefit of Medicaid expansion on cancer death rates on a national scale. We now have evidence that Medicaid expansion has saved the lives of many people with cancer across the US,” said lead author Anna Lee, MD, radiation oncology fellow at Memorial Sloan-Kettering Cancer Center, New York City.

“Better access to quality cancer care, in this case through state expansion of Medicaid, leads to fewer deaths,” said ASCO Chief Medical Officer and Executive Vice President Richard L. Schilsky, MD.

Videoconference Intervention and Coaching

A study that has particular relevance in the COVID-19 era found that a videoconference coaching intervention helped to reduce anxiety and distress for caregivers who live more than one hour away from the cancer patient they were caring for [Abstract 12123].

The randomized controlled trial was conducted at a large urban comprehensive cancer center, and patients undergoing treatment for any type of cancer were included.

Distance caregivers were randomized to Arm 1 (4 monthly videoconferences with a nurse practitioner or social worker focused on information and support, participation in a patient’s appointment with the oncologist, and access to a specially-designed website for distant caregivers); Arm 2 (no coaching sessions but the other 2 components); and Arm 3 (access to the website only).

At the completion of the study of 441-patient-caregiver dyads, only Arm 1 showed a significant 21% improvement in anxiety over time, and a significant improvement in distress over time (54.3%).

The majority of the caregivers (71%) were female, 65% were Caucasian, and 65% were the child of the patient.

“Distance caregivers experience a tremendous amount of anxiety and distress – often greater than people with cancer themselves. With COVID-19, the challenges distance caregivers face are now the same challenges facing many local caregivers who can’t attend their loved ones’ appointments [with the oncologist].

“Our videoconference intervention shows that it’s possible to meaningfully reduce anxiety and distress for distance caregivers through fairly simple technology,” said lead author Sara L. Douglas, PhD, RN, professor in oncology nursing and assistant dean for research at the Case Western Reserve University School of Nursing, Cleveland, OH.

By John McCleery

April 27, 2020 - 04:04 pm comments0 Comments

On April 23, 2020, the AACR held a preview press conference in advance of its first-ever Virtual Annual Meeting I taking place April 27 – 28, 2020, necessitated by the Covid-19 pandemic.

“We are living in unprecedented times and certainly not what we imagined when we were planning this meeting one year ago. The virtual meeting will permit rapid sharing of new results and cutting-edge information,” said AACR President Elaine R. Mardis, PhD.

AACR President-Elect Antoni Ribas, MD, PhD, focused on clinical trials to be presented at eight Plenary Sessions during the virtual meeting, and added that there would be a wide array of other presentations featured over the two-days, including mini-symposia, posters, award-winning lectures, and a special session on coronavirus and cancer.

A second virtual meeting is planned for June 22 – 24, 2020—the AACR Virtual Annual Meeting II.

Opening Plenary Session

The I-SPY 2 trial compared the combination of the checkpoint Inhibitor durvalumab in combination with the PARP inhibitor olaparib and paclitaxel versus chemotherapy alone in patients with high-risk HER2-negative stage II/III breast cancer (Abstract CT011).

Patients who received the combination therapy had significantly improved pathological compete response (a surrogate endpoint) over the chemotherapy alone treatment arm, including those with triple-negative breast cancer, which is considered a hard-to-treat subtype.

“This study showed that triple therapy is better than chemotherapy in shrinking breast cancer,” said Dr. Ribas.

Abstract CT012 presents results of the IMspire 150 trial in previously untreated patients with BRAFV600-positive advanced melanoma. The addition of the checkpoint inhibitor atezolizumab to cobimetinib and vemurafenib led to more durable responses, improved progression-free survival, and increased duration of response compared with those treated with cobimetinib plus vemurafenib plus placebo.

“The IMspire 150 study is practice-changing,” noted Dr. Ribas.

Commenting on the first two abstracts where immunotherapy is combined with chemotherapy and/or targeted drugs, Dr. Ribas said, “The toxicities and the economic implications are important. The toxicities [of these regimens] will be presented at the virtual meeting, but the economic implications will require additional analysis and will be forthcoming.”

A separate study in BRAF-mutated melanoma (Abstract CT013) showed that continuous dosing of dabrafenib and trametinib nearly doubled progression-free survival (from 5.5 months to 9 months) compared with intermittent dosing but did not improve survival. The study suggests that continuous dosing may delay resistance to these two agents.

IMbassador250 was a Phase 3 trial (Abstract CT014) that compared atezolizumab plus enzalutamide versus enzalutamide alone in patients with metastatic prostate cancer. Despite hopes of improving outcomes with the checkpoint inhibitor, no survival benefit was observed compared with enzalutamide alone.

Early Detection and ctDNA

Dr. Ribas singled out two abstracts (CT021 and CT022) from a Plenary Session on early detection and ctDNA screening that used two different liquid biopsy tests—a cell-free DNA multicancer early detection test in individuals with suspicion of cancer, and the DETECT test in 10,000 women with no history of cancer. Both studies found that this cancer screening modality was able to confirm the presence of cancer as well as the site of origin of the cancer before many of these cancers would be diagnosable otherwise.

“These studies in thousands of patients provide support for using these tests. This session will be remembered as when we saw the big data to support use of these tests. We need regulatory approval but I don’t think it will take that long to enter practice,” said Dr. Ribas.

Dr. Mardis commented by pointing out that both researchers used these tests in different but innovative ways to pick up the site of cancer. “This minimizes follow-up testing that occurs clinically. It would be a good problem to have if we picked up cancers too early to be otherwise diagnosed that required no treatment. I don’t think that will happen because the focus is on cancers detected late where the need is most pressing for cancer detection.”

A third presentation at the same session on ctDNA described a liquid biopsy that can detect minimal residual disease (MRD) following surgery for non-small-cell lung cancer well ahead of clinical relapse, in addition to defining the clonality of relapsing disease (Abstract CT023).

Adoptive Cell Transfer Therapy

A Plenary Session on adoptive cell transfer therapy will focus on next-generation CAR-T products. Abstract CT052 presents results of the first-in-human data on TruCARTMGC027 a universal CAR-T product developed using CRISPR-based technology for the treatment of adult relapsed/refractory T-cell acute lymphoblastic leukemia (ALL). Four of five patients had an MRD-negative response.

Abstract CT051 describes a small study of a bispecific CAR-T construct in children and young adults with relapsed/refractory ALL. Eight of 11 patients who completed treatment had objective responses (four MRD-negative complete responses and four partial responses).

Covid-19 and Cancer

A clinical Plenary Session taking place on Day 2 of the virtual meeting will be devoted to Covid-19 and cancer. Dr. Ribas will chair this session that will feature speakers from Wuhan, Italy, and New York City and cover experience in using oncology drugs to treat Covid-19 patients.

Some drugs used to treat cancer patients may be repurposed to treat the consequences of Covid-19. “This category benefits from the experience of cancer and hematologic treatment for similar complications, such as respiratory distress and cytokine release syndrome [CRS],” said Dr. Ribas.

According to Dr. Ribas, tocilizumab is used to treat CRS in patients treated with CAR-T. JAK inhibitors used to treat certain cancers are also being tested in patients with Covid-19 and respiratory distress. Other cancer drugs may also find a role in treating the complications of Covid-19.

“The confluence between cancer research and the field of virology should enable more rapid translation,” he said.

By John McCleery

 

April 07, 2020 - 12:04 am comments0 Comments

I don’t have to tell anyone that the novel coronavirus has caused an unprecedented global crisis. However, with attention rightfully so on COVID-19, and the strain on hospitals and front-line clinical staff, what you may not realize is the impact of this devastating health event on patients with cancer and their providers.

Due to the disease and treatment, patients with cancer are immunocompromised, and also, because on average they tend to be older, are extremely susceptible to COVID-19. Their oncologists, nurses, and clinical staff are tasked with trying to manage patients in this new locked-down world, while keeping themselves and their facilities COVID-19 free. Thankfully, the Centers for Medicare & Medicaid Services (CMS) has provided a veritable lifeline to patients that will literally save countless lives by cutting through the red tape and allowing providers to use telehealth in an unprecedented manner.

CMS’ expansion of telehealth in terms of how oncology providers can use it to manage their patients is nothing short of dramatic and lifesaving. This week, I heard from a community oncologist in Oregon who has been able to treat an 81-year-old patient with a new diagnosis of acute myeloid leukemia using telehealth. The patient is being managed primarily as an outpatient, with labs drawn at his residence center. Weekly physician-patient telehealth visits are allowing the oncologist to keep close tabs on the patient’s health and cancer progression. I heard from a practice in Texas where one of their oncologists teamed up with a liver specialist to coordinate care via telehealth visits for a patient who would have had to travel 266 miles roundtrip for office visits.

We may be able to effectively shut the country down in the face of this crisis, but, unfortunately, cancer cannot be shut down. Fortunately, with over half of Americans with cancer being treated by independent community oncology practices, cancer will not get the better of us as COVID-19 rages. Armed with CMS Administrator Seema Verma’s expansive new telehealth tool, oncologists are able to manage their patients, with the goal of prioritizing treatment and keeping them out of the hospital environment, whether that be in the emergency room or hospitalized. Under the new CMS telehealth expansion, providers are able to furnish 80 more services via telehealth. As the providers of cancer care to the majority of cancer patients in America, it is crucial that community oncology practices stay open and active for patients as cancer and cancer care does not stop during this time of national emergency.

I applaud CMS for especially considering the needs of rural and low-income patients when cutting through the telehealth red tape. Clinicians can now evaluate patients who have audio-only phone systems, a major leap forward that eases the burden on patients who do not have access to, or cannot operate, more advanced technology. In an unprecedented crisis, unprecedented actions like these keep care providers and patients safe while maintaining continuous treatment for cancer and other life-threatening diseases.

With an understandable focus on the doom and gloom of COVID-19, community oncology practices must charge forward ensuring that their patients are safely managed and treated. They can’t stop because cancer won’t stop. Fortunately, telehealth is proving to be a valuable tool in their arsenal and is already making important life-saving differences.

Ted Okon is executive director of the Community Oncology Alliance. Learn more at www.CommunityOncology.org.

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