Diagnosis of adenocarcinoma of the lung, a major subtype of non-small lung cancer (NSCLC), nowadays triggers mandatory testing of tumor tissue for alterations in four genes: EGFR, ALK, ROS1, and more recently, BRAF. If present, these alterations predict sensitivity to specific targeted drugs approved by the U.S. Food and Drug Administration (FDA) that work better and often longer than standard chemotherapy, and are better tolerated.
However, there are many more targetable/actionable genomic alterations (also known as “drivers”) in NSCLC. This blog post will briefly discuss most of them, with the goal of promoting molecular testing for more than the four “usual suspects” mentioned above. Some patients with these alterations may benefit from FDA-approved drugs or from enrollment in clinical trials that are testing additional drugs and drug combinations. Continue reading…
“Triplet therapy for advanced, BRAF V600-mutant melanoma led to objective responses in 73% of a small group of patients enrolled in a phase I trial, according to updated results reported at the 2017 ESMO Annual Congress in Madrid.
“Ongoing follow-up in the trial showed that 11 of 15 patients responded to the combination of pembrolizumab (Keytruda), dabrafenib (Tafinlar), and trametinib (Mekinist). Seven of the 11 responding patients had not progressed after a median follow-up of 20 months. ‘Updated results of the phase I portion of the KEYNOTE-022 trial confirmed previously reported efficacy of this triplet combination,’ said Antoni Ribas, MD, PhD, a professor of medicine, surgery, and molecular and medical pharmacology at the University of California at Los Angeles. ‘The results demonstrated durability of responses. No late or unexpected toxicities occurred with longer follow-up. The randomized phase II portion of KEYNOTE-022 is ongoing.’ ”
“Phase II results demonstrated that nearly half of patients with resectable stage IIIB/C BRAF V600-mutant melanoma achieved pathologic complete response (pCR) with neoadjuvant combination therapy consisting of dabrafenib (Tafinlar) and trametinib (Mekinist). Additionally, no patients experienced disease progression during the neoadjuvant treatment, said Alexander M. Menzies, MD, who presented the data at the 2017 ESMO Congress in Madrid.
” ‘Nearly 50% of our patients had a complete eradication of their melanoma at the time of surgery. Fifty percent had some remaining melanoma in the surgical specimen, but every patient had some degree of tumor shrinkage on therapy,’ said Menzies, a medical oncologist and senior research fellow at Melanoma Institute Australia in Sydney, Australia. ‘These are patients who otherwise would just have surgery and then have observation. And, these are patients who are at very high risk, probably the highest risk of recurrence without further therapy.’ ”
There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…
“More than one-fourth of patients with advanced BRAF V600-mutant melanoma remained alive at 5 years after treatment with the combination of dabrafenib (Tafinlar) and trametinib (Mekinist), long-term follow-up from a randomized trial showed.
“In the subgroup of patients with normal baseline lactate dehydrogenase (LDH) and fewer than 3 organ sites with metastases, half remained at alive at 5 years. No new safety signals emerged during long-term follow-up, as reported at the 2017 ASCO Annual Meeting in Chicago.”
“The FDA approved use of dabrafenib in combination with trametinib for treatment of patients with metastatic non–small cell lung cancer whose tumors harbor BRAF V600E mutations, according to the agents’ manufacturer.
“The combination of dabrafenib (Tafinlar, Novartis) — a BRAF inhibitor — and trametinib (Mekinist, Novartis), a MEK1/2 inhibitor — is the first targeted treatment approved in the United States specifically for patients with BRAF V600E–positive metastatic NSCLC.”
By 2050, the number of deaths due to malignant melanoma in the U.S. could be three times lower than peak levels reached before 1960. Researchers presented the data behind this prediction at the 2017 European Cancer Congress in January.
It is unclear how much of this anticipated decline in deaths can be attributed to the availability of new, effective treatments. However, it is obvious that much-increased awareness of sunlight exposure as the single factor most responsible for the development of skin melanoma has contributed to lower incidence of the disease.
In any case, the armament of treatments available for metastatic melanoma is currently such that this diagnosis has transformed from being almost universally fatal (even just a few years ago) into a being largely treatable. Since 2011, the U.S. Food and Drug Administration (FDA) has approved eight new drugs for melanoma. Continue reading…
In spring of 2014, Peter Fortenbaugh noticed what appeared to be a tick that had bitten his lower calf. “It turned out not to be a tick, but it didn’t really go away,” he says.
The spot began to grow and bulge, and in October, Peter showed it to his primary care doctor, who referred him to a dermatologist to remove it. At the time, Peter recalls, it did not occur to him that the growth could be serious.
“I was actually very concerned about skin cancer because I spent a lot of time out in the sun sailing,” Peter says. “I put on a tremendous amount of sunscreen and protection, but never on my legs…I never connected the dots.”
However, a biopsy of the growth came back positive for melanoma. Peter, who lives in Palo Alto, California, with his wife and three children, immediately reached out to several doctors in the San Francisco Bay Area, and all had the same advice: “Take it out, take a biopsy.” Continue reading…
“A team of Dana-Farber scientists has released new research with an important message about precision medicine: Sequencing the genes of brain tumors in kids could point to treatments that target their genetic abnormalities and therefore have the best chance of being effective. At least one of those drugs is already on the market, Novartis’ Tafinlar (dabrafenib), approved by the FDA to treat other types of cancer but still readily available to pediatric oncologists who may want to try it in their patients.”