MEK Inhibitor Disappoints in KRAS-Mutant NSCLC

Excerpt:

“A targeted combination therapy for patients with KRAS-mutant non-small cell lung cancer (NSCLC) did not improve overall survival (OS) or progression-free survival (PFS), researchers reported.

“The phase III, randomized SELECT-1 trial compared the experimental MEK inhibitor selumetinib, in combination with docetaxel (Taxotere), with docetaxel and placebo as second-line therapy in patients who failed a previous line of therapy, explained Pasi Jänne, MD, PhD, of the Dana Farber Cancer Institute in Boston, and colleagues.

“After a follow-up of approximately 1 year, median OS in the selumetinib combination group was 8.7 months versus 7.9 months in the docetaxel plus placebo group (hazard ratio 1.05, 95% CI 0.85-1.30, P=0.64), they wrote in JAMA.

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Array BioPharma Announces Positive Top-Line Results from Part 2 of the Phase 3 COLUMBUS Study of Binimetinib and Encorafenib for BRAF-Mutant Melanoma

Excerpt:

“Array BioPharma (Nasdaq: ARRY) today announced top-line results from Part 2 of the Phase 3 COLUMBUS study evaluating binimetinib, a MEK inhibitor, and encorafenib, a BRAF inhibitor, in patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The primary analysis of Part 2 compared progression free survival (PFS) in patients treated with binimetinib 45mg twice daily plus encorafenib 300mg daily (COMBO300) to patients treated with encorafenib 300mg daily as a single agent. The median PFS for patients treated with COMBO300 was 12.9 months compared to 9.2 months for patients treated with single agent encorafenib, with HR of 0.77 [95% CI 0.61-0.97, p=0.029]. COMBO300 was generally well-tolerated and reported dose intensity and adverse events were consistent with COMBO450 results in COLUMBUS Part 1. Part 2 was designed specifically to assess the contribution of binimetinib to the combination of binimetinib and encorafenib by reducing the dose of encorafenib to 300mg in the combination arm to allow for a comparison of equal doses across arms. Further results from Part 2 will be presented at a medical meeting during the second half of 2017.”

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Super Patient: Peter Fortenbaugh Faces the Uncertainty of Pioneering Melanoma Treatment


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…


Immunotherapy, MEK Inhibitor Combo Effective for BRAF Wild-Type Melanoma

Excerpt:

“The combination of atezolizumab (Tecentriq) and cobimetinib (Cotellic) may lead to a higher overall response (ORR) and a longer progression-free survival (PFS) than either agent alone in patients with metastatic melanoma, according to findings presented at the 2016 Society for Melanoma Research (SMR) Annual Meeting.

“The findings were part of a phase Ib dose-escalation and dose-expansion study, which looked at the PD-L1 inhibitor and MEK inhibitor together in advanced solid tumors. Data on a cohort of 22 patients with ocular melanoma (n = 2) and non-ocular melanoma (n = 20) was presented at the meeting. Among patients in the non-ocular cohort, the ORR was 45% and the disease-control rate (complete response, partial response, and stable disease) was 75%. Median PFS was 12 months (95% CI, 2.8-16.7).”

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Array BioPharma and Pierre Fabre Announce COLUMBUS Phase 3 Study of Encorafenib plus Binimetinib For BRAF-Mutant Melanoma Met Primary Endpoint

Excerpt:

“Array BioPharma (Nasdaq: ARRY) and Pierre Fabre today jointly announced top-line results from Part 1 of the Phase 3 COLUMBUS (Combined LGX818 Used with MEK162 in BRAF Mutant UnresectableSkin Cancer) study evaluating LGX818 (encorafenib), a BRAF inhibitor, and MEK162 (binimetinib), a MEK inhibitor, in patients with BRAF-mutant advanced, unresectable or metastatic melanoma. The study met its primary endpoint, significantly improving progression free survival (PFS) compared with vemurafenib, a BRAF inhibitor, alone.”

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Lead NEMO Author Shares Excitement With Binimetinib in NRAS-Mutant Melanoma

Excerpt:

“For patients with NRAS-mutant melanoma who progress following treatment with an immunotherapy agent, the MEK inhibitor binimetinib offers a promising option, explains Reinhard Georg Dummer, MD.

“Results of the open-label phase III NEMO trial, which were presented during the 2016 ASCO Annual Meeting,1 most recently demonstrated the agent’s potential. In the study, binimetinib was found to reduce the risk of progression or death by 38% when compared with dacarbazine in this subgroup of patients.

“Additionally, median progression-free survival (PFS) with binimetinib was 2.8 months versus 1.5 months with dacarbazine (HR, 0.62; 95% CI, 0.47-0.80; P <.0001). The objective response rate with binimetinib was 15%, including 1 complete response, compared with 7% for dacarbazine.”

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Binimetinib Improves PFS in NRAS-Mutated Metastatic Melanoma

Excerpt:

“The novel MEK inhibitor binimetinib resulted in improved progression-free survival (PFS) and response rates vs dacarbazine in patients with NRAS-mutated advanced unresectable/metastatic melanoma, according to results of an open-label phase III trial.

“ ‘NRAS mutations are present in approximately 20% of all patients with metastatic melanoma,’ said Reinhard Dummer, MD, of the University Hospital Zurich in Switzerland. ‘It activates the MAPK pathway and by this drives cell proliferation and anti-apoptotic mechanisms.’ Preclinical studies have shown that NRAS-mutant melanoma is sensitive to MEK inhibition, and binimetinib inhibits both MEK1 and MEK2. A phase II study showed clinical activity in NRAS-mutant metastatic melanoma.

“The NEMO trial included 402 patients randomized 2:1 to receive either binimetinib (269 patients) or dacarbazine (133 patients; 19 were not treated and were not evaluated for safety). Patients were either treatment-naive or had progressed on or after immunotherapy. The primary endpoint of the study was PFS. The results were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting held earlier this month in Chicago (abstract 9500).”

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3-Year Follow-Up Data for Dabrafenib/Trametinib Confirm Results of Combo in Melanoma

Excerpt:

“Three-year follow-up data from the phase III COMBI-d study was presented at the 2016 ASCO Annual Meeting, revealing impressive overall survival (OS) and progression-free survival (PFS) data for the dabrafenib (Tafinlar) and trametinib (Mekinist) combination therapy for patients with BRAF-mutant metastatic melanoma.

“At the February 15, 2016 data cutoff for the 3-year analysis, 58% of patients remained on therapy. The 3-year PFS rate with the combination was 22% versus 12% with single-agent dabrafenib. The 3-year OS rate was 44% with dabrafenib plus trametinib compared with 32% with dabrafenib alone.

” ‘This is the longest OS follow-up among randomized phase III trials evaluating a BRAF plus MEK inhibitor in patients with BRAF-mutant metastatic melanoma,’ said lead investigator Keith T. Flaherty, MD, Massachusetts General Hospital Cancer Center and Professor of Medicine, Harvard Medical School. ‘With additional follow-up, and now 3-year maturity, dabrafenib plus trametinib continued to show significant benefit over dabrafenib monotherapy, despite crossover.’ ”

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Experts Grapple With Nuances of Navigating New Frontier in Melanoma

“Emerging data showing improved survival with targeted and immunotherapeutic approaches are rapidly altering the standard of care for patients with melanoma. For BRAF-positive patients with metastatic or unresectable melanoma, the standard of care includes a BRAF inhibitor in combination with a MEK inhibitor. For patients with or without BRAF mutations, there are immunotherapeutic options available in frontline and in resistant disease settings.

“Questions remain, however, in terms of how to optimally sequence and/or combine both targeted agents and immunotherapies. And, for BRAF-mutant disease, when is it appropriate to switch from a targeted approach to an immunotherapeutic one?”