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ASCO: Studies Highlight Resource Utilization, Immunotherapy, Targeted Therapy, and Physical Fitness

More than 30,000 attendees from all over the world are expected at the 2013 Annual Meeting of ASCO, the “Mercedes Benz” of cancer meetings in the United States. Seven of the more than 4,700 abstracts to be presented were featured at the official pre-meeting Presscast on May 15, 2013.

The featured abstracts can be categorized as follows:

  • 3 studies showed that “less is more” in cancer treatment;
  • 2 studies focused on promising results with novel immunotherapies in melanoma and other cancers;
  • 1 study featured Phase I results with the first-in-class PI3delta kinase inhibitor in the treatment of chronic lymphocytic leukemia (CLL); and
  • 1 study showed that physical fitness (as distinct from level of physical exercise) lowers men’s risk of developing and dying from lung and colorectal cancers.

“Less is More”

Stakeholders involved in fine-tuning resource utilization will be interested in a study showing that standard low-dose radiation is superior to high-dose radiation in the treatment of non-small cell lung cancer (NSCLC); that surveillance alone is a valid strategy for patients with stage I seminoma following primary treatment with orchiectomy; and that most relapses of diffuse large B-cell lymphoma (DLBCL) are picked up by physical exam or lab test abnormalities rather than by routine imaging.

A randomized, controlled Phase 3 trial in 464 patients with stage III NSCLC compared standard dose radiation (60 Gy) versus high-dose radiation (74 Gy) in patients treated with standard chemotherapy and found that lower dose radiation achieved superior survival and caused fewer treatment-related deaths.

While earlier studies suggested that higher doses of radiation could provide better local control, this study clearly demonstrates that it is associated with much shorter survival, said Jeffrey D. Bradley, MD, Washington University School of Medicine in St. Louis, MO. “The biological reasons for failure of the high dose with respect to overall survival and local-regional control are not readily apparent,” he said.

A long-term study of 1,822 patients suggests that adjuvant chemotherapy and radiation can be avoided in men with stage I seminoma, and surveillance is sufficient follow-up after surgery.

In the study, 99.6% of men followed by a 5-year surveillance program were alive 10 years after diagnosis. In the study, 19.5% of patients had a relapse, which was treated with radiotherapy, chemotherapy, or surgery.

Surveillance was defined as 5 years of scheduled physical exams, chest x-ray exams, CT scans, and blood tests.

“This means that for every 1,000 men followed on a surveillance program, only 4 die within 10 years,” said Mette Sakso Mortensen, MD, Copenhagen University, Denmark.

A separate study showed that routine use of CT or PET scans did not improve detection of relapse in patients with DLBCL. The vast majority of relapses were identified by abnormal physical exams, laboratory test findings, and/or development of symptoms.

At about 5 years of follow-up after initial treatment, the relapse rate was 20%. At the time of relapse, 68% of patients were symptomatic, 42% had an abnormal physical exam, and 55% had abnormal blood tests. Planned surveillance scans detected relapses in only 8 out of 537 patients (1.5%) with no symptoms before relapse.

Lead author Carrie A. Thompson, MD, Dana-Farber Cancer Institute in Boston said that patients should be vigilant about reporting symptoms between scheduled visits.

“These 3 studies will certainly change or influence practice,” said Clifford Hudis, MD, ASCO’s President-Elect.

Anti-PDL-1 Immunotherapy

Two preliminary Phase 1 studies showed that using an anti-PD-L1 targeted antibody to unlock “brakes” that prevent T-cells from attacking tumor cells is a strategy worth pursuing in melanoma and other advanced cancers.

The first study evaluated MPDL3280A (Genentech), an anti-PD-L1 antibody, in 140 patients with advanced lung, melanoma, kidney, and gastric cancers that had progressed on previous treatments. The study found that the drug was safe and achieved robust tumor shrinkage, with the best results seen in lung cancer and melanoma. The study has expanded to 275 patients. Further study is needed, and Phase 2 and 3 studies are planned. Ultimately, the drug will probably be combined with other anti-cancer therapies, including immunotherapy and targeted therapy, said Roy S. Herbst, MD, PhD, Yale Cancer Center, New Haven, CT.

A separate Phase 1 study evaluated the combination of ipilimumab and the anti PD-L1 antibody nivolumab (Bristol Myers Squibb) in 37 patients with inoperable stage III and IV melanoma, with highly encouraging responses, even in patients who did not previously respond to ipilimumab. Side effects were manageable in this trial, and a randomized Phase 3 trial of the combination as first-line therapy for advanced melanoma will be mounted soon. Lead author was Jedd D. Wolchok, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York City.

PI3K Inhibitor

A Phase 1 study in 54 patients with treatment-resistant CLL showed that the first-in-class PI3K inhibitor idelalisib (Gilead Sciences) was effective in delaying the time to progression by about 17 months. This is better than what would be expected in a sixth-line therapy, which might usually delay time to progression by about 6 to 12 months, said Jennifer Brown, MD, PhD, Dana-Farber Cancer Institute. Side effects were manageable.

Investigators were enthusiastic about both anti-PD-L1 antibodies and the novel PI13K inhibitor. If further study confirms the benefit of idelalisib, it will join ibrutinib as a potential advance in treating CLL; ibrutinib is a Bruton’s Tyrosine Kinase inhibitor that has had encouraging Phase II results in CLL and is now in Phase 3 development.

Fitness and Cancer Outcomes

Several studies have shown that physical exercise has beneficial effects in preventing recurrence of several types of cancer. A new study looks at a different measure of physical status – physical fitness, which can be objectively quantitated on maximal exercise tolerance testing by units of fitness called metabolic equivalents (METS).

For the first time, a study has shown that being physically fit reduces the odds of developing lung and colorectal cancer, and the odds of dying of lung, colorectal, and prostate cancer. “This is the first study to explore fitness as a marker of future cancer risk prognosis,” said lead author Susan Lakoski, MD, University of Vermont in Burlington.

The study, based on Medicare claims data, included 17,049 men who had a single cardiovascular fitness assessment at a mean age of 50 years as part of a preventive health program offered at the Cooper Institute in Dallas, TX.

In men in the highest quintile of physical fitness, the risk of being diagnosed with lung cancer or colorectal cancer was reduced by 68% and 38%, respectively, compared with men in the lowest quintile of physical fitness. Fitness level had no impact on risk of developing prostate cancer.

However, among men who developed lung, colorectal, or prostate cancer, those at a higher level of fitness in their 50s had a lower risk of dying of any of these cancers, as well as of cardiovascular disease. As small as a 1 MET improvement in fitness reduced the risk of cancer-related death by 14% and the risk of death related to cardiovascular disease by 23%.

Another important finding was that low levels of physical fitness were associated with an increased risk of cancer and cardiovascular disease even in non-obese men, suggesting that patients should improve their levels of physical fitness regardless of body weight.

By: Alice Goodman

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