Here are just a few of the studies highlighted during the American Society of Clinical Oncology (ASCO) annual meeting, held May 31 through June 4, 2013, at McCormick Place in Chicago. The meeting, based on the theme “Building Bridges to Conquer Cancer,” drew approximately 30,000 cancer specialists from around the world.
Drug Shortages Force Oncologists to Ration, Turn to Pricier Alternatives
A study by the University of Pennsylvania Abramson Cancer Center and Perelman School of Medicine in Philadelphia found that 83% of oncologists who participated in a recent survey said they had been unable to prescribe a preferred chemotherapy agent due to drug shortages over the previous 6 months.
Topping the list of drugs that have been in short supply were leucovorin and liposomal doxorubicin, said Keerthi Gogineni, MD, of the Abramson Cancer Center, who presented results of the survey at the ASCO clinical science symposium. The survey found that 73 oncology drugs were periodically unavailable in 2003, with escalating shortages, including 129 reported in 2007 and 211 in 2010. Approximately 94% of oncologists surveyed felt that patients had been affected by the shortages.
The survey was conducted from March 2012 to March 2013 and included 500 randomly selected US oncologists from the ASCO membership list, equally representing each region of the country. Seventy-eight percent of respondents said they adapted to drug shortages by switching to a different drug regimen or substituting a drug partway through therapy, whereas 43% said they had to delay treatment. In addition, 37% of respondents said they had to decide which patient should receive the drug when faced with too little of the drug and too many patients. At the same time, oncologists reported having to omit and reduce doses or refer patients to other facilities that had more of the drug.
Shortages were not more common in any region of the country, nor were they any more frequent at community-based private practices than at university-based academic practices.
When drugs were substituted, they often involved replacing a generic drug with a more expensive option. For example, levoleucovorin was substituted for leucovorin, resulting in a 30- fold increase in cost. Meanwhile, capecitabine was substituted for 5-fluorouracil, amounting to a 140-fold greater cost for one cycle of colon cancer treatment.
The shortages also affected clinical trials by preventing or delaying enrollment or leading to a suspension of trial participation. Approximately 70% of oncologists said they had not been given formal guidance on how to manage allocating drugs during a shortage, although those in academic practices were more likely to have guidance.
According to Richard Schilsky, MD, chief medical officer of ASCO, some physicians anecdotally have reported using the more expensive drugs as standard of care which, in turn, drives up medical costs.
Combined Immunotherapies May Be Better for Advanced Melanoma
A phase 1 study evaluating the effectiveness of combining ipilimumab (Yervoy) with the investigational antibody drug nivolumab indicates that the combination led to lasting tumor shrinkage in approximately half of patients with aggressive, advanced melanoma. Ipilimumab is a standard treatment option for patients with advanced melanoma while nivolumab has shown promise for both melanoma and other cancers. Both drugs target immune system checkpoints (PD-1 for the latter and CTLA-4 for the former) on immune cells—helping the immune system to better fight cancer.
The proof-of-principle study, led by Jedd Wolchok, MD, PhD, a medical oncologist at Memorial Sloan-Kettering Cancer Center in New York, generated complete and near-complete response rates not seen before for single-agent immunotherapy treatment of melanoma. The study confirms that the combination approach has strong potential, he said. The trial involved patients with inoperable stage 3 and stage 4 (metastatic) melanoma who had undergone up to 3 prior therapies. They were assigned to 6 different treatment arms. The results reported at the ASCO meeting were based on 52 patients who had received concurrent treatment with the drugs in 3 completed treatment arms.
Tumor shrinkage rates in the 3 arms were 21%, 53%, and 50%, with the highest rates in patients who received both drugs in the highest doses. Three out of 4 patients experienced tumor reduction in the first 3 months, a rate that is faster than with ipilimumab alone. Sixteen of the 52 (31%) had tumor shrinkage of more than 80%. Although data are still preliminary on the other arms, they suggest that patients who initially had little benefit from ipilimumab alone had significant response after receiving nivolumab.
Side effects have been manageable, the authors said. A randomized phase 3 trial of the nivolumab/ipilimumab combination was scheduled to begin in June 2014.
First-Line Bevacizumab Not Recommended in Newly Diagnosed Glioblastoma
A Radiation Therapy Oncology Group (RTOG) phase 3 study has found that bevacizumab (Avastin) added to the standard of care (chemoradiation [CRT] with temozolomide) as the firstline treatment of glioblastoma did not improve median overall survival.
Although the combination was associated with longer progression-free survival, it did not reach its prespecified target, said Mark Gilbert, MD, of the University of Texas MD Anderson Cancer Center in Houston, who presented the results of the study, known as RTOG 0825. The study was a randomized, double-blind, placebo-controlled trial designed to evaluate the effectiveness of bevacizumab, which is an antibody targeted against vascular endothelial growth factor A (VEGF-A). The growth factor is elevated in glioblastoma.
Researchers evaluated 637 newly diagnosed glioblastoma patients in the study. They were randomly assigned to CRT combined with standard-of-care temozolomide and placebo (n = 317) or CRT with temozolomide and 10 mg/kg of intravenous bevacizumab (n = 320) every 2 weeks. Prior to these therapies, all patients received 3 weeks of CRT. If their disease progressed, the patients were allowed to cross over to the bevacizumab arm.
Median follow-up occurred at 20.5 months and found that median overall survival was 15.7 months for patients receiving bevacizumab plus standard of care compared with 16.1 months for patients receiving only standard therapy. Progression-free survival was longer for patients who received the combined treatment (10.7 months) versus only standard of care (7.3 months). Adverse events associated with bevacizumab were higher for patients receiving the drug, and included hypertension, deep vein thrombosis, and significant hemorrhagic events.
In discussing the study, Howard Fine, MD, of New York University, pointed out that as many as 30% of patients may have discontinued bevacizumab as a result of adverse events, thus leading to the lack of significance. In addition, with chronic use, bevacizumab changes glioblastoma from highly vascular tumors to nonvascular tumors, which do not respond to the drug in most patients, he said. For that reason, he added, future studies should define markers for bevacizumab response in first-line therapy and consider its use with other agents that inhibit anti-VEGF-A-associated invasiveness.