Immunotherapy for Cancer

The latest approval of a cancer drug by the US Food and Drug Administration (FDA) changes the paradigm of cancer treatment — the new indication specifies a genetic defect without any mention of tumor types. It allows the drug to be used in any cancer that harbors the specified genetic defect, wherever the tumor appears in the body.

What: Historically, the US Food and Drug Administration (FDA) has approved cancer treatments based on where in the body the cancer started — for example, prostate or breast cancers. For the first time, the FDA approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.

Details: The new approval is for the immunotherapy pembrolizumab (Keytruda, Merck & Co), which is already approved for use in several different tumor types, including melanoma and lung cancer. But this latest approval covers the use of pembrolizumab in tumors that have microsatellite instability-high (MSI-H) or are mismatch repair deficient (dMMR). These defects are found most commonly in colorectal, endometrial, and gastrointestinal cancers but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland, and other places, the agency notes.

Microsatellite instability & immunotherapy: It’s not just colorectal cancer: The results from that trial showed that patients with colorectal cancer with normal DNA repair (microsatellite stable) had zero response to pembrolizumab, whereas those with MSI and deficient DNA repair had a 50% response rate, she said. In addition, about 20% had stable disease. This is much higher than has been seen with immunotherapy in other tumor types, where fewer than 20% patients respond. But the trial also included patients with any solid tumor and MSI, and these patients also showed the 50% response rate and 20% stable disease results.

Downsides: Common side effects of pembrolizumab include fatigue, itchiness, diarrhea, decreased appetite, rash, fever, cough, dyspnea, musculoskeletal pain, constipation, and nausea. The drugs can also cause serious immune-mediated side effects, including lung, liver, kidney, or colon inflammation, endocrine problems.

Action point: All patients with advanced cancer who have had at least one standard therapy should be tested to see if their tumor harbors these genetic defects.

I’m Dr. Michael Hunter.

http://www.medscape.com/viewarticle/880537

The Future of Cancer Care: Therapy Based on Genomics Improves Survival

DNA Strands

Treatment for lung cancer has traditionally been based on the tumor’s histology (what it looks like under the microscope), but a new approach of basing treatment on genomic features has now been shown to result in better survival.

Results from the Lung Cancer Mutation Consortium (LCMC) show that patients who received genotype-directed therapy lived more than a year longer than those who did not.

The evidence that using targeted agents improves survival in lung cancer has been very difficult to show in clinical trials, but the current study shows that such an approach is not only feasible but successful. In fact, the study heralds a new era in the management of patients with a variety of cancers, Dr. Boris Pasche (Wake Forest University, USA) explains.

The Study: The LCMC, a collaborative, 14-center study led by Mark G. Kris, MD, from Memorial Sloan-Kettering Cancer Center, in New York City, tested tumors from 1007 patients with metastatic (spread to distant sites; incurable) lung adenocarcinomas for the presence 10 oncogenic driver mutations and then used the results to select agents that would target the drivers. The study was conducted from 2009 through 2012, and the patients’ tumors were tested for at least 1 gene, with full genotyping (testing for 10 genes) performed in 733 patients. For the other patients, the primary reason for the inability to test for all 10 genes was insufficient tissue.

The Small Print: An cancer driver was found in 466 (64%) of the patients who underwent full genotyping. So-called KRAS mutations were the most frequent, found in 182 (25%), followed by sensitizing EGFR in 122 (17%) and ALK rearrangements in 57 (8%). Less common drivers were other EGFR in 29 (4%), 2 or more genes in 24 (3%); ERBB2 (formerly HER2) in 19 (3%); BRAF in 16 (2%), PIK3CA in 6 (<1%), MET amplification in 5 (<1%), NRAS in 5 (<1%), and MEK1 in 1 (<1%). These results were then used to guide the choice of targeted therapy.

The Evidence: Overall, among 938 patients with adequate data, the median survival was 2.7 years. For patients with an oncogenic driver treated with targeted therapy, the median survival was 3.5 years, for patients with an oncogenic driver who were not treated with targeted therapy, the median survival was 2.4 years, and for patients with no driver identified, the median survival was 2.1 years (P < .001).

Among the different drivers that were identified, the longest survival was seen in patients with ALK-positive tumors (4.3 years).

“We are at the point now where we may be able to offer patients other treatments by studying the genomic features of their cancer. Until recently, we could not afford to do it because it cost about a million dollars for one genome. Now it’s as low as $900 to do the genome of a tumor, and it’s likely that will become even cheaper. And with better software, we would also be able to assess the unique features of that tumor vs other tumors and vs the normal DNA of that patient, and this is really the major change,” he said.

I’m Dr. Michael Hunter, and welcome to the future.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: JAMA. 2014;311:1988-206; Medscape 20 May 2014

Advanced Breast Cancer: Better Sleep Predicts Longer Survival

woman sleeping serenely

What You Need to Know: Sleep efficiency, a ratio of time asleep to time spent in bed, is predictive of survival time for women with advanced breast cancer. This is the first study to demonstrate the long-term detrimental effects of objectively quantified sleep on survival in women with advanced cancer.

Among the women diagnosed with advanced breast cancer, those who sleep efficiently – not necessarily for longer period – are likely to live longer than those who do not get quality sleep, a study indicated. Sleep efficiency refers to the ratio of time asleep to time spent in bed.

“Good sleep seems to have a strongly protective effect, even with advanced breast cancer,” said Oxana Palesh, an assistant professor at Stanford University. “We were surprised by the magnitude of the relationship between sleep quality and overall survival even after we accounted for medical and psychological variables that typically predict survival.”

There is no association between sleep duration and survival, the findings of the research showed.

Details, details: The study involved 97 women with advanced breast cancer who had a mean age of 55 years. Objective sleep parameters were measured by wrist actigraphy for three consecutive days. Higher sleep efficiency was significantly associated with lower mortality over the ensuing six years. Mean survival was 68.9 months for efficient sleepers compared with 33.2 months for participants with poor sleep efficiency. A 10 percent increase in sleep efficiency reduced the estimated hazard of subsequent mortality by 32 percent, further analysis showed.

My Take: Sleep disruption may lead to diminished immune function or impaired hormonal stress responses that are more directly responsible for the decrease in survival. This study is in the journal Sleep. I’m Dr. Michael Hunter.

Reference: http://www.business-standard.com/article/news-ians/better-sleep-ups-survival-period-of-breast-cancer-patients-114050300722_1.html

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Can a simple handshake predict cancer survival rates? Yes.

Doctor and patient meeting handshake greeting

New acquaintances are often judged by their handshake. Research has now recognized the simple squeeze as an important diagnostic tool in assessing strength and quality of life among critical care patients.

In a study published in the journal, Support Care Cancer, Concordia professor Robert Kilgour and his colleagues at the McGill (Montreal, Canada) Nutrition and Performance Laboratory confirmed a link between handgrip strength and survival rates.

The test was simple: 203 patients fighting advanced-stage cancers squeezed a device known as a dynamometer with their dominant hand. The instrument then measured peak grip strength.

Because it requires minimal equipment, this method of evaluation is both portable and practical, says Kilgour: “This measure is one of several to categorize patients according to the severity of their disease. It can help determine interventions they may need, whether clinical, nutritional or functional.”

While other diagnostic tests rely on a patient’s self-reporting or examine related factors such as decreased body weight,the handgrip test directly focuses on body strength. Its precision allows doctors to better assess a patient’s decline. Clinicians typically classify patients by percentiles; those in the bottom 10th percentile are in the most serious condition, while those in the 25th are somewhat stronger. In most cases, slowing a patient’s decline and maintaining a decent quality of life can be a significant accomplishment.

Kilgour and his colleagues believe the grip test may help all categories of patients, especially those in the 25th percentile. At this stage, even modest interventions, like starting exercise or a diet change, can yield results, boosting both the physical and mental health of patients.

My Take: Seems logical, at least for those with advanced cancer. I hope to never see you as a patient with cancer, but if I do, please don’t crush my hand too much! I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad:  Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: R. D. Kilgour, A. Vigano, B. Trutschnigg, E. Lucar, M. Borod, J. A. Morais. Handgrip strength predicts survival and is associated with markers of clinical and functional outcomes in advanced cancer patients. Supportive Care in Cancer, 2013; 21 (12): 3261 DOI: 10.1007/s00520-013-1894-4