Melanoma: New Drugs and New Challenges (Part 2 of 2)


Editor’s note: This is part 2 of a 2-part post on the latest research in melanoma. To learn about research into drug combinations for melanoma that may work better than single drugs, check out Melanoma: New Drugs and New Challenges (Part 1 of 2).

As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…


Metastatic Prostate Cancer Cases Surge, Adding to Screening Controversy

Excerpt:

“A new study documents a decade-long increase in the number of men who have incurable prostate cancer at their initial diagnosis, an ominous finding that prostate cancer-screening proponents have been predicting.

“Both screening and diagnosis of early-stage prostate cancer have declined, coinciding with recommendations from an influential government advisory panel. In 2008, the U.S. Preventive Services Task Force said not to do routine PSA blood testing of men over age 74. And in 2012, it said to not screen any men – not even those at high risk – because the harms of unnecessary treatment outweigh the benefits of catching cancer early.”

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Study Suggests Men with Metastatic Prostate Cancer Should Be Tested for Inherited Mutations

Excerpt:

“Inherited mutations in DNA-repair genes, such as the BRCA genes, can increase cancer risk. A new study shows that DNA-repair mutations are significantly more common in men with metastatic prostate cancer compared with men whose prostate cancer hasn’t spread. This suggests all men with advanced prostate cancer should be tested for inherited DNA-repair mutations to help select the most effective therapies and provide information on family risk.”

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Concurrent SRS, Immunotherapy Improved Response in Melanoma Brain Mets

Excerpt:

“Undergoing immunotherapy within a month of stereotactic radiosurgery (SRS) for the treatment of melanoma brain metastases resulted in an improved response to treatment compared with undergoing the two treatments with a longer amount of time between them, according to the results of a study published in Cancer.

“Patients in the study who underwent the two therapies within 4 weeks of each other had a significantly greater median percent reduction in lesion volume regardless of whether SRS occurred before or after immunotherapy.”

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Ipilimumab plus T-VEC Shows Promise for Metastatic Melanoma

Excerpt:

“Talimogene laherparepvec plus ipilimumab demonstrated safety and efficacy among patients with untreated, unresectable advanced melanoma, according to study results published in Journal of Clinical Oncology.

“ ‘Tumor immunotherapy has become an established treatment of metastatic melanoma and is being increasingly applied to other cancer types,’ Igor Puzanov, MD, MSCI, associate professor of medicine at Vanderbilt University School of Medicine, and colleagues wrote. ‘A hallmark of tumors likely to respond to immunotherapy is a lymphocyte-predominant tumor microenvironment. To date, immunotherapy designed to promote lymphocyte accumulation within established tumors, activate lymphocyte function and cytotoxicity, and prevent T-cell suppression has shown the most promise.’ ”

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Pembrolizumab Shows Activity in Brain Metastases from NSCLC, Melanoma

Excerpt:

“Pembrolizumab demonstrated therapeutic activity in brain metastases of patients with non–small cell lung cancer or melanoma, according to early results of an ongoing randomized phase 2 trial.

“ ‘In the United States, about 50,000 patients with metastatic melanoma or non–small cell lung cancer develop brain metastases every year. … At diagnosis, 10% of patients with metastatic NSCLC have brain metastases and another 30% develop brain involvement,’ Sarah B. Goldberg, MD, MPH, assistant professor in the department of medical oncology in the Smilow Cancer Hospital at Yale School of Medicine, and colleagues wrote. ‘Many effective drugs in development have not been well studied for central nervous system penetrations, and patients with untreated brain metastases are excluded from most clinical trials.’ ”

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Safety, Survival Advantages of Radium-223 Continue to Offer Benefit in mCRPC

Excerpt:

“The manageable safety profile of radium-223 dichloride (Xofigo) compared with other radiopharmaceuticals is appealing to oncologists treating castration-resistant prostate cancer (CRPC) that is metastatic to the bone, says Richard G. Stock, MD.

“ ‘With previous radiopharmaceuticals, there has been a limitation with bone marrow toxicity,’ said Stock, senior faculty, Radiation Oncology, Mount Sinai Hospital. ‘Radium-223 really spares the bone marrow to a much greater degree than prior treatments, and that is why it has been embraced and much more widely utilized than any of the other radiopharmaceuticals.’ ”

“The FDA approved radium-223 in May 2013 based on findings from the phase III ALSYMPCA trial. In the study, radium-223 demonstrated a median overall survival of 14.9 months compared with 11.3 months with placebo for patients with bone-metastatic CRPC (HR, 0.70; P <.001).”

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Radiation Plus ADT Boosts Survival in Metastatic Prostate Ca (CME/CE)

Excerpt:

“A large contemporary analysis of men with metastatic prostate cancer has found that adding radiotherapy to androgen deprivation therapy resulted in substantially better survival than androgen deprivation alone.

“With a median follow-up of 5.1 years, giving prostate radiotherapy plus androgen deprivation was associated on univariate analysis with a longer median overall survival of 53 versus 29 months, for a hazard ratio of 0.562 (95% CI 0.498-0.635, P0.001). The effect held in multivariate, propensity score, and landmark analyses — with the last yielding improved overall survival estimates at 3, 5, and 8 years, reported Chad. G. Rusthoven, MD, of University of Colorado School of Medicine, Denver, and colleagues in the Journal of Clinical Oncology.

“The estimates were 62% versus 43% for 3 years, 49% versus 25% for 5 years, and 33% versus 13% for 8 years (HR 0.562, 95% CI 0.498-0.635, P0.001).”

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Can Patients Discontinue Immunotherapy and Still Benefit?

Excerpt:

“At present in clinical practice, immunotherapy with anti-PD-1 agents is administered indefinitely until intolerable toxicities or progressive disease sets in. But there has been anecdotal evidence that patients who stop treatment may still derive benefit, and now there is evidence of this from a post hoc analysis of a randomized study.

“It comes from the CheckMate 069 trial that evaluated the combination of nivolumab (Opdivo, Bristol-Myers Squibb Company) and ipilimumab (Yervoy, Bristol-Myers Squibb Company) vs ipilimumab alone in patients with metastatic melanoma.

“New results from a post hoc analysis of this trial, presented at the recent American Society of Clinical Oncology (ASCO) 2016 Annual Meeting (abstract 9518), show that a subgroup of patients who discontinued combination immunotherapy because of treatment-related adverse events achieved an impressive overall response rate (ORR) of 66%.”

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