September 2012, Vol 1, No 4

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Targeted Drug Leads to Marked Responses in NSCLC

Don Schrader

Conference News

A drug that targets a previously overlooked mutation led to objective responses in 8 of 14 patients with advanced non–small cell lung cancer (NSCLC), according to results of a proof-of-principle study.

Some patients had symptomatic relief within days of beginning treatment with crizotinib, Alice T. Shaw, MD, PhD, reported at the Annual Meeting of the American Society of Clinical Oncology. The drug targets a ROS1 mutation that occurs in 1% to 2% of NSCLC tumors.

Overall, the drug was well tolerated, as the most common adverse event was a mild visual disturbance that affected almost all of the patients.

“ROS1 rearrangement defines a distinct subset of non–small cell lung cancer,” said Shaw, an attending physician in thoracic oncology at Massachusetts General Hospital in Boston. “Crizotinib demonstrates marked antitumor activity in patients with advanced ROS1-positive non–small cell lung cancer. These results validate ROS1 as a therapeutic target in lung cancer.”

Some patients had substantial resolution of tumors within weeks of starting treatment, she added.

Identified about 20 years ago, ROS1 has a poorly defined normal function and only recently was found to play a role in a subset of NSCLC tumors. ROS1 activates signaling pathways common to several receptor tyrosine kinases, said Shaw.

Of 15 patients treated to date, 12 remained on therapy, and 14 could be evaluated for response. In addition to the 8 patients who had objective responses, 4 others had stable disease for 8 weeks or longer, resulting in a disease control rate of 79%. Median treatment duration was 25.7 weeks.

Aside from visual impairment, adverse events included transient liver enzyme elevation, diarrhea, hypophosphatemia, peripheral edema, dysgeusia, nausea, vomiting, elevated alkaline phosphatase, neutropenia, and sinus bradycardia.

Invited discussant Gregory Riely, MD, PhD, said the results add to the ongoing transformation of NSCLC from a single entity into a heterogeneous disease associated with multiple genetic mutations and profiles.

“We can’t solely identify these patients by smoking history, ethnicity, age. We really need to test all patients,” said Riely, a thoracic oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Despite the limited clinical experience, the marked responses that occurred in some of the patients have convinced Riely to start giving crizotinib to all patients with confirmed ROS1-positive NSCLC.

Conference News - September 19, 2012

Severe Diarrhea Associated With Molecularly Targeted Agents Can Impact Quality of Life and Healthcare Resource Utilization

A preliminary report of a meta-analysis of clinical trials of molecularly targeted therapies shows that they are not benign and can add to the toxicity of standard chemotherapy. In particular, increased rates of oral mucositis and diarrhea are reported with several FDA-approved agents. Increased mucositis seen with bevacizumab and erlotinib [ Read More ]

Conference News - September 19, 2012

Risk of Cardiotoxicity With Targeted Therapies Exaggerated

Molecularly targeted therapies change the vascular milieu and can cause hypertension, fluid retention, and thromboembolic phenomena. However, the absolute risk of cardiotoxicity is much lower with targeted therapies compared with anthracyclines, stated Michael S. Ewer, MD, from the MD Anderson Cancer Center in Houston, Texas, at the recent meeting of [ Read More ]