September 2012, Vol 1, No 4

← Back to Issue

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.

Uncategorized - September 19, 2012

Surgery Versus Observation for Localized Prostate Cancer

For men with localized prostate cancer detected by prostate-specific antigen (PSA) level, treatment with radical prostatectomy did not significantly reduce mortality compared with observation, according to overall results of the large, randomized, controlled PIVOT trial (Wilt TJ, et al. N Engl J Med. 2012; 367:203-213). All-cause mortality and prostate-specific mortality [ Read More ]

Uncategorized - September 19, 2012

Weightlifting in Women at Risk for Breast Cancer–Related Lymphedema

Although weightlifting reduced the need for lymphedema treatment by 50% compared with standard treatment in breast cancer survivors who participated in the Physical Activity Lymphedema (PAL) trial, weightlifting is not without its own risks. A retrospective analysis of the PAL trial found that the rate of injury was higher in [ Read More ]