Important Data and Treatment Advances Reported in GIST and in Pancreatic and Liver Cancers 


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Tumors are now being characterized at the molecular level... This type of information will be practice-changing.

—Daniel Chung, MD

The 10th annual Gastrointestinal Cancers Symposium, held recently in San Francisco, was jointly sponsored by ASCO, the AGA (American Gastroenterological Association), ASTRO (American Society for Radiation Oncology), and the SSO (Society of Surgical Oncology).

“We seek to present the newest scientific and clinical developments in gastrointestinal cancers at this meeting, and we focus not only on treatment but also on diagnostic testing and preventive strategies,” said Daniel Chung, MD, Associate Professor of Medicine at Harvard Medical School and Chair of the Steering Committee. “The 10th anniversary of this meeting provided a unique opportunity to look back at where we have been and then define where the field should be going in the next 10 years. One of the most important changes is that tumors are now being characterized at the molecular level, and this information can be used to determine prognosis and response to treatment. This type of information will be practice-changing.”

The ASCO Post covered key presentations in longer articles, and offers the following news briefs about other important developments reported at the symposium. For more in-depth reports from the meeting, see pages 1 and 16.

Surgery after Imatinib Improves Survival in GIST

South Korean investigators reported that surgery after imatinib (Gleevec) for the treatment of gastrointestinal stromal tumors (GIST) prolonged survival.1 The study involved 134 patients with metastatic or recurrent GIST who were treated with imatinib alone or imatinib plus surgery to remove residual tumor (followed by more imatinib). Patients were eligible for the study if they responded to prior imatinib treatment for at least 6 months.

Seong Joon Park, MD, a fellow in the Department of Oncology at Asan Medical Center in Seoul, reported that the median progression-free survival in the nonsurgical group was 42.8 months, but this increased to 87.7 months in the group that underwent surgery (P = .001). Median overall survival has not been reached in the surgery arm, and was 88.8 months in the imatinib-alone arm (P = .001). Surgical management reduced mortality risk fivefold. 

In a multivariate analysis, low initial tumor burden was associated with longer overall survival; low initial tumor burden, female gender, and a specific alteration in the KIT gene (KIT exon 11 mutation, which is associated with improved responses) were associated with delayed disease progression. Even after applying propensity score and inverse-probability-weighting adjustment, surgical management was associated with better clinical outcomes.

“It is difficult to establish treatment guidelines based on the retrospective design of this study, but it provides good evidence supporting a clinical practice that is already widely adopted,” Dr. Park said.

S-1 Superior to Gemcitabine in Pancreatic Cancer

Preliminary results from a phase III trial conducted in Japan showed that patients with pancreatic cancer who received adjuvant chemotherapy with S-1, an oral fluoropyrimidine currently used in Asia (and to some extent Europe) but not approved in the United States, had a 44% lower risk of dying, compared to standard treatment with gemcitabine.2

Although the study was designed as a noninferiority trial, the data found S-1 to be superior to gemcitabine. “Our survival data were much stronger than expected,” said Katsuhiko Uesaka, MD, PhD, Medical Deputy Director at Shizuoka Cancer Center Hospital, Shizuoka, Japan. “Our interim analysis showed S-1 to be superior to gemcitabine in overall survival, and therefore it may be considered as a new standard treatment for resected pancreatic cancer patients in Japan.”

The study included 385 patients with resected stage I to III pancreatic cancer who received gemcitabine or S-1. On interim analysis, the 2-year survival rates were 70% with S-1 vs 53% for gemcitabine (P < .0001 for noninferiority; P < .0001 for superiority).

S-1 was well tolerated in the Asian population, with more than 70% of patients able to complete treatment. However, the drug has proven more toxic in Caucasians (primarily, diarrhea), therefore, the findings are not currently applicable to non-Asian populations, experts said. Dr. Uesaka maintained that with dose adjustments, “I expect S-1 may be applicable to all patients with pancreatic cancer.” A U.S. phase III trial is currently exploring S-1 for the treatment of stomach cancer.

Chemoradiotherapy Following Induction Chemotherapy in Pancreatic Cancer

For the treatment of locally advanced pancreatic cancer following induction chemotherapy, chemoradiotherapy with capecitabine (Xeloda) was more effective and less toxic than chemoradiotherapy with gemcitabine, in the phase II SCALOP trial presented by Somnath Mukherjee, MD, FRCP, FRCR, of the Gray Institute for Radiation Oncology & Biology at the University of Oxford in the United Kingdom.3 The study confirms what is already standard practice in the United States.

Patients first received three cycles of gemcitabine and capecitabine (GEMCAP) combination chemotherapy. Patients with stable or responding disease, tumors ≤ 6 cm, and performance status 0 or 1 were randomly assigned to an additional cycle of GEMCAP followed by radiation administered at 50.4 Gy in 28 daily fractions in combination with either capecitabine on weekdays or gemcitabine weekly.

The primary endpoint was proportion of patients progression-free at 9 months, which was 62.9% with capecitabine/radiotherapy and 51.4% with gemcitabine/radiotherapy. Median overall survival was 15.2 months and 13.4 months, respectively, a 50% reduction in risk (P = .025). The 12-month overall survival was 79.2% in the capecitabine group and 64.2% in the gemcitabine group.

Patients treated with capecitabine/radiotherapy also had significantly less grade 3 and 4 hematologic toxicity (0% vs 18.4%; P = .007) and nonhematologic toxicity (11.1% vs 26.3%), though the latter was not statistically significant.

Dr. Mukherjee suggested their findings should establish “capecitabine/radiotherapy as a template regimen for future trials investigating radiotherapy dose escalation and combination with novel radiosensitizers.”

Statins May Reduce Mortality from Liver Cancer

Patients with hepatocellular carcinoma who took statins had a 30% lower mortality rate than those who did not, in a study from The University of Texas MD Anderson Cancer Center, Houston.4 Statins were used in addition to local and systemic therapy or surgical resection in 644 patients followed over 10 years. The median overall survival for all patients was 19.2 months, and 10.7% reported statin use.

Young Kwang Chae, MD, MPH, MBA, of MD Anderson Cancer Center, reported that median overall survival was higher among statin users, 22.2 months vs 18 months for nonusers (P = .04). For hepatocellular carcinoma patients without cirrhosis, median overall survival was 31.7 months vs 21.8 months, respectively (P = .06), and the reduction in mortality was 30%, but the protective effect was not seen in patient with cirrhosis, whose median overall survival was 17.5 months with statin use and 18.9 months without (P = .8).

The positive effect on overall survival remained significant after adjusting for age, sex, race, staging, hepatitis C and B history, liver cirrhosis, treatment, alcohol use, and diabetes (P = .03). Although patients taking statins were older and had more cardiovascular disease, diabetes, and other comorbidities, they actually lived longer, the authors noted.

Dr. Chae pointed out that hepatocellular cancer is a very vascular disease, and preclinical evidence supports the antitumoral activity of statins. ■

Disclosure: Dr. Uesaka has received honoraria from Lilly and Taiho Pharmaceutical. Dr. Mukherjee has served in a consultant or advisory role for Celgene. Drs. Chung, Park, and Chae reported no potential conflicts of interest.

References

1. Park SJ, Ryu M-H, Ryoo B-Y, et al: The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST. 2013 Gastrointestinal Cancers Symposium. Abstract 62. Presented January 24, 2013.

2. Uesaka K, Fukutomi A, Boku N, et al: Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer (JASPAC-01 study). 2013 Gastrointestinal Cancers Symposium. Abstract 145. Presented January 25, 2013.

3. Mukherjee S, Hurt C, Griffiths G, et al: SCALOP: Results of a randomized phase II study of induction chemotherapy followed by gemcitabine or capecitabine based chemoradiation in locally advanced pancreatic cancer. 2013 Gastrointestinal Cancers Symposium. Abstract LBA146. Presented January 25, 2013.

4. Chae YK, Kaseb AO, Mohamed H, et al: The association between statin use and hepatocellular cancer outcome. 2013 Gastrointestinal Cancers Symposium. Abstract 165. Presented January 25, 2013.



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