Thousands of melanoma patients in Europe have no access to new life saving drugs

Unacceptable inequalities in the availability and accessibility of new and effective cancer medications across Europe.

Over 5000 patients with metastatic melanoma in Europe are denied access to new, life-saving drugs every year, according to a survey presented at the ESMO 2016 Congress in Copenhagen. Metastatic melanoma is an aggressive and deadly skin cancer. With innovative targeted therapy and immunotherapy, patients can survive for many years. Unfortunately, new therapies are expensive so, according to a survey conducted by Dr Lidija Kandolf-Sekulovic, over 5000 patients with metastatic melanoma in Europe have no access to these drugs.

Before 2011 there were no effective treatment options for metastatic melanoma patients, but that has changed tremendously in the last 5 years. We now have medicines which can prolong overall survival of these patients to more than 18 months and, in some patients, durable responses lasting up to 10 years have been reported. However, access to these medicines is limited and patients and physicians are facing increasing difficulties to obtain them. This is especially the case for Eastern and South Eastern European countries, where a majority of patients are still treated with palliative chemotherapy that does not prolong overall survival,” said Kandolf-Sekulovic.

The survey showed that in Western Europe 70% of patients were treated with innovative medicines, while in Eastern Europe less than 10% of patients had access to the latest treatment recommended by current European Guidelines (ESMO, EORTC/EADO).

The study found that the BRAFi+MEKi combination (one of the first-line treatments besides immunotherapy for BRAF mutated metastatic melanoma) was registered in 75% of Western European countries and fully reimbursed in 58%. In Eastern Europe, the treatment was registered in 42% of countries and only reimbursed in 18%, with time-consuming administrative work needed to obtain the medicines in all cases.

The survey estimated that around 19.250 metastatic melanoma patients are treated every year in Europe and nearly 7.450 (39.7%) in Eastern and South-Eastern Europe. Of these patients, 5.128 (69%) do not have the access to first-line therapy according to European guidelines. Overall, it can be estimated that in Europe 5.228/19.250 (27%), i.e. almost one third of all metastatic melanoma patients, do not have access to innovative medicines.

In Europe, about 1 in every 100 people will develop melanoma at some point in their life, but important variations exist from one country to another. This number is increasing in almost all European countries. Melanoma is slightly more frequent in females than in males and more frequent in Switzerland, the Netherlands and the Scandinavian countries (Norway, Sweden and Denmark), where about 20 out of 100,000 people are diagnosed each year. From 1999-2012 there has been a 78% recorded increase in Germany. Similar increases were recorded also in the United States, Australia, Norway and Denmark, as well as countries in South-Eastern Europe.

Kandolf-Sekulovic explained: “Our study raises ethical questions on the inequalities that affect survival based on the country of residence in Europe. It is not new that disparities in healthcare can lead to disparities in overall survival of patients, but these disparities are becoming even sharper for patients with chemotherapy resistant metastatic melanoma in whom durable responses lasting for years can be seen in up to 20% of patients if treated with innovative medicines. In European healthcare systems that declare universal access to healthcare, these inequalities must be overcome.”

Dr Alexander Eniu, Chair of the ESMO Global Policy Committee, said: “This study confirms what ESMO has highlighted in the past: access to the best treatment according to evidence-based clinical guidelines such as ESMO’s, is not equal across Europe. ESMO advocates for equal access to treatment and care, which is the fundamental right of any patient. Despite the encouraging rate of new medicine development, there are still unacceptable inequalities in the availability and accessibility of new and effective cancer medications across Europe.”

The present study focuses on melanoma but the ESMO-led European Consortium Study on the availability and accessibility of anti-neoplastic medicines across Europe found that the same was true for other types of cancer, especially rare cancers, in countries with lower economic levels. It is important to continue to provide health authorities with data, and to carry on calling attention to the difficulties patients with incurable diseases are facing, in the hope that equal access will soon be a reality, at least in Europe,” said Eniu.

This everyday situation which is a source of a large frustration for metastatic melanoma patients, their families and physicians, needs to be addressed urgently by all stakeholders. We need harmonisation of reimbursement procedures throughout Europe, adjusted programmes for early access to innovative medicines in countries with delayed reimbursement and sustainable pricing for these life-saving drugs,” concluded Kandolf-Sekulovic.

European Society for Medical Oncology Congress 2016 Copenhagen, Denmark

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Chemotherapy and exercise: The right dose of workout helps side effects

Researchers at the University of Rochester Wilmot Cancer Institute discovered something simple and inexpensive to reduce neuropathy in hands and feet due to chemotherapy – exercise.

The study, involving more than 300 cancer patients, is to be presented this weekend and honored as a “Best of ASCO” among 5,800 abstracts at the world’s largest gathering of oncologists, the American Society of Clinical Oncology (ASCO) annual meeting 2016. More than a dozen other Wilmot scientists also were invited to present data at the meeting.

Investigators in the exercise study directly compared the neuropathic symptoms in non-exercisers to the pain among patients who took part in a specialized six-week walking routine with gentle, resistance-band training at home.

The exercisers reported significantly fewer symptoms of neuropathy – which includes shooting or burning pain, tingling, numbness, and sensitivity to cold – and the effects of exercise seemed to be most beneficial for older patients, said lead author Ian Kleckner, Ph.D., a biophysicist and research assistant professor in Wilmot’s Cancer Control and Survivorship program. Kleckner also won an ASCO Merit Award in the pain and symptom management category, and was invited to give a talk about his work.

Not all chemotherapy drugs cause neuropathy, but 60 percent of people with breast cancer and other solid tumors who receive taxanes, vinca alkaloids, and platinum-based chemotherapies will likely suffer this type of side effect, Kleckner said. Neuropathy is more commonly associated with diabetes or nerve damage. No FDA-approved drugs are available to prevent or treat chemotherapy-induced neuropathy, he added.

Wilmot’s specialized exercise program, called EXCAP (Exercise for Cancer Patients), was developed several years ago at the UR by Karen Mustian, Ph.D., M.P.H., an associate professor in the Cancer Control program. In recent years she has copyrighted and evaluated EXCAP in several clinical trials. Last year at ASCO, Mustian presented data from a randomized, controlled study of 619 patients showing that EXCAP reduced chronic inflammation and cognitive impairment among people receiving chemotherapy. Kleckner’s study involved a subset of patients from Mustian’s trial, which is the largest phase 3 confirmatory exercise study ever conducted among cancer patients during chemotherapy. Their work is funded by the National Cancer Institute and Mustian’s PEAK lab.

Exercise – as a cancer prevention tool and potential treatment – is a hot topic among the nation’s oncologists and their patients.

Kleckner, a longtime drug-free body builder and former college rugby player, said he’s committed to understanding more deeply the benefits of exercise for cancer patients. “Exercise is like a sledgehammer because it affects so many biological and psychosocial pathways at the same time – brain circuitry, inflammation, our social interactions – whereas drugs usually have a specific target,” he said. “Our next study is being designed to find out how exercise works, how the body reacts to exercise during cancer treatment, and how exercise affects the brain.”

Mustian is also giving two talks at ASCO, about the use of exercise in geriatric cancer patients and how innovation can help exercise investigators reach their goals.

Our program at the University of Rochester, which now includes more than  half a dozen researchers, is becoming a real powerhouse in exercise oncology,” Mustian said. “Twelve years ago when we started this work a lot of people said it was not safe for most cancer patients to exercise. Now we know it can be safe when done correctly, and that it has measurable benefits. But more exercise isn’t always better for patients who are going through chemo – so it’s important to continue our work and find a way to personalize exercise in a way that will help each individual.”

Counseling patients at risk for cancer over the phone reduces costs and access burdens

Patients who receive results of genetic tests over the phone do not experience increased anxiety or depression.

Delivering genetic test results to patients at risk for cancer-causing genetic mutations over the phone helps to ease cost and transportation burdens and, compared to receiving results in person, does not cause patients additional stress, according to a new study from the Abramson Cancer Center of the University of Pennsylvania which will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (abstract 1502). The findings suggest delivering results of complex genetic tests to at-risk patients over the phone may be an effective way to reduce burdens and costs for patients with cancer or at risk for cancer, according to the study’s lead author, Angela R. Bradbury, MD, an assistant professor of Medicine and Medical Ethics & Health Policy in Penn’s Perelman School of Medicine.

Genetic testing for cancer susceptibility is now an essential component of oncology care, but many patients have to travel to large centers to get genetic testing,” Bradbury said. “While health care providers deliver results for many tests over the phone, results of genetic tests have traditionally been delivered in-person because of the complexity, potential for increased levels of distress, or confusion over what the results could mean. However, our study shows that delivering results over the phone does not generate more distress, even for those with positive results and even now that we are using multi-gene testing.”

In the study, more than 900 patients who had received in-person counseling prior to undergoing genetic testing for cancer-causing mutations were randomly assigned to receive test results in person or over the phone. Test results were delivered over the phone by 22 genetic counselors across five participating sites. Participants were asked to report their feelings of anxiety and depression and knowledge about genetics both before and after test results were delivered.

Results showed that those who received results over the phone did not have any more anxiety, worry about cancer risk, or depression than those whose services were delivered in person, even among participants whose tests were positive for cancer-causing genetic mutations. Patients who received results over the phone also reported fewer barriers to accessing genetic counseling services than those who received results in person.

Delivering results over the phone allows us to provide services to patients at risk for cancer-causing genetic mutations for whom cost and access burdens might otherwise be prohibitive,” Bradbury said. “By providing services over the phone and removing the need to travel to a doctor’s office or hospital, we’re limiting the disruption to a patient’s daily routine, but maintaining the patient-provider relationship and delivering high-quality cancer genetic services.

Additional results of the study suggest there may be small differences in how well patients understand test results when receiving information over the phone as compared to in-person, though the clinical significance remains unclear. The authors say further data is needed to understand this finding before widespread adoption of phone disclosure of genetic test results is implemented.

The overall goal of this research is to decrease barriers to genetic testing while ensuring that at-risk patients receive appropriate and accurate information,” said senior author Susan Domchek, MD, executive director of the Basser Center for BRCA at Penn’s Abramson Cancer Center. “This study is a step in that direction, and shows that providers can deliver quality services in a way that is convenient for patients.

The American Society of Clinical Oncology (ASCO) annual meeting 2016, Chicago, Illinois

Hispanic and black young adult cancer patients more likely to die of their disease

Hispanic white and non-Hispanic black cancer patients between ages 15 and 29 may be more likely than same-aged white patients to die of their disease, according to a University of Colorado Cancer Center study presented at the American Society for Clinical Oncology (ASCO) Annual Meeting 2016.

The finding is partially but not wholly explained by socioeconomic status, meaning that in addition to the health risks associated with low socioeconomic status or stage of presentation, there are additional health risks associated specifically with these racial/ethnic identities.

As with many disparities, you have to identify the problem before you can fix it,” says Meryl Colton, MS, medical student at University of Colorado School of Medicine, who performed the analysis with Adam L. Green, MD, investigator at the CU Cancer Center and pediatric oncologist at Children’s Hospital Colorado.

The study used data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) database to compare the overall rate of death in the two years following cancer diagnosis for the three above-mentioned racial/ethnic groups, as well as people with Medicaid or no insurance compared to private insurance. For example, taking the chance of a young-adult white patient dying within two years of being diagnosed with liver cancer as a baseline of “1”, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient’s chance of dying is 1.76.

“What this means is that black and Hispanic young adult patients are almost 75 percent more likely to die after being diagnosed with liver cancer than are white young adult patients,” Colton says.
This increased risk of mortality for black and Hispanic patients, as well as those without private health insurance, holds true across cancer types including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.

Much of this disparity is explained by the overlap between low socioeconomic status and racial/ethnic minority status, meaning that the increased chance of dying after a cancer diagnosis is due in part to conditions associated with having less financial resources no matter one’s race/ethnicity. However, even after controlling for insurance status, an indicator of socioeconomic status, and stage of presentation, disparities in death rates after cancer diagnosis remained between these racial/ethnic groups, implying an influence of race/ethnicity independent of financial resources.

This is a starting point,” says Colton. “Part of an analysis like this is saying, ‘hey, this exists!’ And now the second part is trying to figure out why this is happening.”

Though additional study is certainly required, Colton points to three possible components of this continuing disparity: The possibility that residual socioeconomic factors could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of these diseases to make cancers more dangerous in certain populations, or the possibility that the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.

This is a population that shouldn’t be getting cancer and it’s devastating when they do,” Colton says. “Knowing that a disparity exists allows us to ask questions that can help ensure everyone receives the best possible care.”

The American Society of Clinical Oncology (ASCO) annual meeting 2016, Chicago, Illinois

Chemoradiation may increase survival for a subset of elderly head and neck cancer patients

The addition of chemotherapy (CT) to radiation therapy (RT) improves survival rates among a subset of elderly head and neck cancer patients, specifically those ages 71 to 79 with low comorbidity scores and advanced disease stage, according to University of Colorado Cancer Center research presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium. While previous research has demonstrated the efficacy of combining CT with RT to improve survival for HNSCC patients, this improvement had not been shown in patients older than 70 years.

Elderly patients have been underrepresented in prospective clinical trials that have defined standards of care for head and neck cancer,” said Sana Karam, MD, PhD, CU Cancer Center investigator, assistant professor of radiation oncology at the University of Colorado School of Medicine, and senior author on the study. “Our study drew on nationwide data to assess more comprehensively how combined therapy impacts this population.”

The authors queried the National Cancer Data Base (NCDB) for records of patients older than 70 years who were treated for non-metastatic oropharyngeal, laryngeal and hypopharyngeal cancers between 1998 and 2011. The NCDB is a jointly-sponsored project of the American College of Surgeons and the American Cancer Society that aggregates data from more than 1,500 facilities accredited by the Commission on Cancer. Sixty-eight percent of the patients received RT alone, and 32 percent received CRT.

​Compared with RT alone, CRT was associated with improved survival in patients age 79 and younger with advanced disease but without comorbid conditions. Collaborators included Dr. Arya Amini, first aurthor on the study, and Drs. Bernard Jones, Antonio Jimeno, Jessica McDermott, David Raben, Debashis Ghosh and Daniel Bowles as co-authors on the study.

Patients who did not see an OS benefit from CRT tended to be age 80 or older, had a comorbidity score of two or greater, presented with less advanced disease, or were treated with three-dimensional RT. Patients age 80 or older with multiple comorbidities trended toward worse OS with CRT, though the difference was only marginally significant.

Findings may aid clinicians in discussing treatment options with their elderly HNSCC patients. Moreover, results of this study could guide future prospective trials to confirm the benefit of multimodality treatment in elderly patients, not only for head and neck cancer but for other cancer sites, as well.

Because the toxicity of concurrent chemoradiation is greater than radiation alone for definitive HNSCC treatment, many clinicians have reservations about offering CRT for elderly head and neck cancer patients,” said Karam. “However, in the era of improved radiation techniques, improved systemic therapy and better supportive care, we find that CRT does, in fact, improve survival for a large segment of this population.

The abstract, “Does Age Matter? Survival Outcomes with the Addition of Concurrent Chemotherapy for Elderly Head and Neck Cancer Patients Undergoing Definitive Radiation Using the National Cancer Data Base,” will be presented in detail as a poster presentation at the 2016 Multidisciplinary Head and Neck Cancer Symposium in Scottsdale, Arizona.

Multidisciplinary Head and Neck Cancer Symposium, 2016, Scottsdale, Arizona, USA.

Why does tamoxifen work better in some women?

The anti-hormone therapy tamoxifen can reduce breast cancer recurrence by about half in women with hormone-sensitive breast cancer. But it works better in some women than others. Researchers are not sure why.

We do know that some tumors are inherently resistant to tamoxifen because of tumor genetic changes,” says Daniel L. Hertz, Pharm.D., Ph.D., an assistant professor in the University of Michigan College of Pharmacy and member of the U-M Comprehensive Cancer Center.

These tumor have found pathways to overcome anti-estrogen treatment. But we also believe some patients may be less likely to benefit from tamoxifen or endocrine therapy because of their genetics,” Hertz says.

One theory is that in some patients, tamoxifen is not activated to the more potent estrogen inhibitor endoxifen. Patients with low levels of endoxifen may have worse outcomes on tamoxifen.
A meta-analysis by the International Tamoxifen Pharmacogenetics Consortium points to genetic variants. Researchers found patients with certain variants on the gene CYP2D6 had worse survival. Later analyses of prospective clinical trials, however, did not find the same link.

New research presented by Hertz at the San Antonio Breast Cancer Symposium examined these prior studies to assess whether errors in genotyping – how they identify the genetic variants – could have accounted for the differing findings. Statistical deviations seen in the original meta-analysis had been attributed to genotyping error. But their secondary analysis revealed that statistical deviations were linked to enrolling patients from multiple institutions, not genotyping error.

Furthermore, advanced statistical modeling from Hertz and colleagues confirms that genotyping error would introduce negligible bias to the analyses of the prospective trials.

Genotyping from the tumor in these prospective clinical trials is not the reason these analyses are negative,” Hertz says. “Either there is some other reason that the later studies were negative or the initial study suggesting CYP2D6 as a marker was falsely positive.”

This leaves more questions than answers about tamoxifen efficacy.

In another study presented in San Antonio, Hertz and colleagues found that variants in CYP2D6 and another gene, CYP2C9, contribute to endoxifen exposure. Hertz suggests that it may not be one single marker that predicts whether tamoxifen works.

At this point we still have a hypothetical association between genotype and efficacy that has not been validated,” he says. “For now, there is no clinical benefit to using CYP2D6 to inform tamoxifen treatment decisions. We need to validate these hypotheses.”

San Antonio Breast Cancer Symposium, Dec. 8-12, 2015

Anti-androgen therapy improves survival for men with cancer recurrence after prostatectomy

Men with prostate cancer who have prostate-specific antigen recurrence following radical prostatectomy have improved survival with radiotherapy and a long-term course of anti androgen therapy.

It is well established that a rising serum prostate-specific antigen (PSA) level is an indication of cancer progression in men diagnosed with prostate cancer and treated with radical prostatectomy (RP). For these patients, adding 24 months of anti-androgen therapy (AAT) during and after salvage radiotherapy (RT) improves overall survival statistically compared with salvage RT alone, according to the long-term results of a clinical trial conducted by the Radiation Therapy Oncology Group (RTOG), now conducting research as NRG Oncology. The RTOG 9601 study results presented today at the plenary session of the 57th Annual Meeting of the American Society for Radiation Oncology (ASTRO) also reveal that the addition of ATT to salvage RT reduces prostate cancer death and the development of metastatic prostate cancer without increasing radiation toxicity.

Over the last 25 years, many men with intermediate-risk prostate cancer have undergone RP, yet many will face recurrence subsequently with a rising PSA,” says lead study author William U. Shipley, M.D., FACR, FASTRO, who is the Andres Soriano Distinguished Professor of Radiation Oncology at the Massachusetts General Hospital and the Harvard Medical School, both in Boston. “Our results show that salvage RT plus peripheral androgen blockade (AAT with bicalutamide), when compared with RT plus a placebo, improved long-term overall survival and reduced death from prostate cancer without adding significantly to radiation toxicity. Because prostate cancer progresses slowly, follow-up of over 12 years was necessary to demonstrate a statistically better patient survival with combined AAT and RT.

With a median follow-up now of 12.6 years, the study results showed the actuarial overall survival at 10 years was 82 percent for the RT plus AAT arm and 78 percent for the RT plus placebo arm (P = 0.036). The 12-year incidence of prostate cancer-related deaths was 2.3 percent for the RT plus AAT arm, compared with 7.5 percent for the RT plus placebo arm. At 12 years, the cancer had metastasized in 51 patients (14 percent) in the RT plus AAT arm, compared with in 83 patients (23 percent) in the RT plus placebo arm. Additionally, late bladder and bowel toxicity were low and similar in both groups, whereas 70 percent of men in the RT plus AAT arm reported swelling of the breasts, compared with 11 percent in the RT plus placebo arm.

Conducted at sites across the United States and Canada from 1998 to 2003, the RTOG 9601 trial enrolled 761 men with prostate cancer who had undergone RP and subsequently developed elevated PSA levels. The patients were randomized to receive either salvage RT plus placebo (377 patients) or salvage RT plus AAT (384 patients).

Further statistical analyses, which are underway, may identify subgroups of patients who may not benefit from hormone therapy added to salvage RT and other subgroups for whom it may be especially beneficial. Also, because anti-androgen therapy, which suppresses testosterone production, is now used more commonly than peripheral androgen blockade with AAT, its use should be evaluated,” says Shipley in regard to next research steps for the population of post-RP patients referred for salvage RT. Shipley also emphasizes the clinical researchers’ gratitude for the willingness of the patients to participate on this and other randomized trials and for the essential role they play in advancing cancer care.

The results of this trial are testament to the importance of phase III randomized controlled trials for determining significant benefits. Congratulations to the trial team for their commitment to obtaining the quality of research data necessary for impacting the clinical care of patients with prostate cancer,” says Walter J. Curran Jr., M.D., an NRG Oncology Group Chairman and Executive Director of the Winship Cancer Institute of Emory University in Atlanta.

57th Annual Meeting of the American Society for Radiation Oncology (ASTRO) 2015 San Antonio, Texas, USA