Oncology experts from all over the globe arrived in Vienna, Austria, to attend the European Society for Medical Oncology (ESMO) 2012 Congress. Attendance broke all records, with 16,394 delegates, many of them from outside of Europe: 1116 from the United States, 539 from Japan, 479 from China, 292 from Argentina, and 258 from Brazil. Following are some highlights from the Presidential Symposia and papers proffered at the meeting.
Bevacizumab Plus Chemotherapy Extends Survival in Platinum-Resistant Ovarian Cancer
Adding bevacizumab to chemotherapy regimens improved response rates and progression-free survival (PFS) in patients with platinum-resistant recurrent ovarian cancer, according to an exploratory analysis of the phase 3 AURELIA trial (Abstract LBA26).1 The study design allowed treatment with 1 of 3 chemotherapy regimens (weekly paclitaxel, pegylated liposomal doxorubicin [PLD], or topotecan).
Bevacizumab improved PFS in the overall analysis of the trial (pooling data from the 3 different regimens). Median PFS was 10.4 months for bevacizumab plus chemotherapy versus 3.9 months for chemotherapy alone.
“Bevacizumab combined with chemotherapy should be considered a new standard option for platinum-resistant recurrent ovarian cancer,” stated lead author Andres M. Poveda, MD, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
The exploratory analysis looked at each of the 3 regimens and found that weekly paclitaxel plus bevacizumab had superior results. As stated above, median PFS was 10.4 months when bevacizumab was added to weekly paclitaxel versus 3.9 months for weekly paclitaxel alone. In the PLD cohort, median PFS was 5.4 months versus 3.4 months, respectively. In the topotecan cohort, median PFS was 5.8 months versus 2.1 months, respectively.
AURELIA randomized 361 patients with platinum-resistant recurrent ovarian cancer treated with up to 2 prior anticancer regimens to chemotherapy alone or chemotherapy plus bevacizumab. The chemotherapy regimen was the investigator’s choice among the 3 regimens. Treatment was continued until unacceptable toxicity or progressive disease occurred.
Overall response rates (ORRs) were superior with the addition of bevacizumab, with the highest response rates observed in the weekly paclitaxel cohort: 51.7% versus 28.8% for chemotherapy alone. ORR was 18.3% and 7.9%, respectively, for the PLD cohort and 22.8% and 3.3%, respectively, for the topotecan cohort.
No significant differences in toxicity were observed, with the exception of more peripheral neuropathy in the weekly paclitaxel cohort and more hand-foot syndrome in the PLD cohort.
Standard of Care for Soft Tissue Carcinoma
Single-agent doxorubicin remains the standard of care as first-line treatment for unresectable or metastatic soft tissue sarcomas, according to results of a phase 3 trial conducted by EORTC and presented at the Presidential Symposium during the ESMO 2012 Congress (Abstract LBA7).2,3 This study is the latest in a string of trials attempting to improve outcomes with doxorubicin by adding other agents.
Soft-tissue sarcomas are a heterogeneous group of tumors that are relatively rare. Overall incidence is approximately 5 per 100,000, said Winette van der Graaf, MD, University of Nijmegen, the Netherlands. The complexity of the tumor types and the relative rarity of the tumors have made it challenging to conduct clinical trials, she added.
This study compared doxorubicin to doxorubicin/ifosfamide plus growth factor support in 455 patients aged 18 to 60 years with locally advanced or metastatic soft tissue sarcomas. This study used a higher dose of ifosfamide (10 g/m2 over 4 days with growth factor support) than previous studies that evaluated this combination.
Treatment was continued every 3 weeks for a maximum of 6 cycles or until the development of progressive disease. At a median follow-up of 56 months, there was no significant difference between the 2 treatment arms in overall survival (OS). Median OS was 14.3 months with the combination of doxorubicin/ifosfamide versus 12.8 months with doxorubicin alone; OS at 1 year was 60% and 51% for the 2 arms, respectively. Doxorubicin/ifosfamide achieved a longer progression-free survival: 7.4 months versus 4.6 months, respectively (P = .003), and higher overall response rates—26.5% versus 13.6%, respectively—but this came with a host of increased toxicity.
Based on these results, van der Graaf said that single-agent doxorubicin should remain the standard of care in the palliative setting. The combination might be useful for selected patients 60 years and younger with large tumors.
T-DM1 Survival Benefit Confirmed in Advanced HER2+ Breast Cancer
T-DM1, an antibody-drug conjugate linking trastuzumab to potent chemotherapy, extended survival, compared with lapatinib plus capecitabine, in advanced HER2+ breast cancer in an updated analysis from the phase 3 EMILIA trial (Abstract LBA12).4
At a median follow-up of about 20 months, T-DM1 reduced the risk of dying by 32%, with a 6-month difference favoring T-DM1. Median overall survival (OS) (death from any cause) was 30.9 months for T-DM1 versus 25.1 months for lapatinib plus capecitabine (P <.0001).
Lead author Sunil Verma, MD, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada, predicted that T-DM1 would be an important treatment option for unresectable locally advanced or metastatic breast cancer.
EMILIA was conducted at 213 sites in 26 countries. The study randomized 991 patients with HER2+ advanced breast cancer who had been treated with trastuzumab and a taxane in a 1:1 ratio to T-DM1 or lapatinib plus capecitabine.
Final progression-free survival (PFS), presented earlier at the 2012 Annual Meeting of the American Society of Clinical Oncology, showed median PFS of 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine, a 35% reduction in the risk of progression favoring T-DM1 (P <.0001).
The OS data presented at ESMO were from the second interim analysis, with a data cutoff of July 31, 2012, when more than 50% of targeted survival events had occurred. Final OS data are expected in 2014.
Grade 3 or higher adverse events occurred more frequently with lapatinib plus capecitabine: 57% versus 41% for T-DM1. Patients in the T-DM1 arm had a higher incidence of thrombocytopenia and increased serum aminotransferase levels, whereas those treated with lapatinib plus capecitabine had higher rates of diarrhea, nausea, vomiting, and hand-foot syndrome. The rates of cardiac dysfunction were very low and similar in both treatment arms.
Initiative Improves Pain Control in Several Countries
The major barriers to implementing adequate pain control for cancer patients on a global scale are restrictive government regulations and lack of access to supplies of morphine. Individual countries may lack morphine suppliers, and regulations in countries where morphine is available may prevent doctors from prescribing doses strong enough to alleviate pain and suffering.
Although a number of international organizations have made strong statements hoping to address the problem of inadequate pain control in cancer patients, this has not led to widespread reform in allowing access to standard care, said Kathleen Foley, MD, Memorial Sloan-Kettering Cancer Center in New York City, at the ESMO 2012 Congress.5 These organizations include the Council of Europe, International Narcotics Control Board, United Nations, World Health Organization, Commission on Narcotic Drugs, and Human Rights Watch, among others.
Foley believes that the problems are solvable, but mainly on a country-by-country basis. She reported success stories for programs funded by the International Palliative Care Initiative. The model for these programs is to identify a “national champion” for cancer pain control within a country, perform a needs assessment, hold a stakeholders meeting, develop task forces, and then formulate a palliative care concept for that country. So far, this has been done in 20 countries.
“We use international documents with symbolic language to guide this policy at a country level. These passionate champions are driving this movement within each country,” she told listeners.
In 2012, the International Palliative Care Initiative funded fellowships in India, Bangladesh, Sri Lanka, Albania, Kyrgyzstan, and Ukraine. Fellows work at the University of Wisconsin in Madison to learn the model described above.
In Romania, 35-year-old restrictive policies were changed. Now there are no limits on daily morphine dose or patient diagnosis. “Past policies were burdensome for patients, and physicians, and these are new beginnings,” Foley said.
In Colombia, a new palliative care law was passed in 2009, and as a result of that law, each district of the country has 1 pharmacy that can provide opioids 24 hours a day.
In Guatemala, efforts are ongoing to bring a morphine supply from Guatemala City to rural areas and to provide further education to legislators, physicians, and patients.
“It’s hard to believe, but in 2012, the first injectable morphine prescription was written in Guatemala, at a hospital where bone marrow transplant is available,” she said.
In Nigeria, the government is now supportive of getting cancer patients access to pain control. In Serbia, a pain policy fellow is working with the government, which has adopted a pain policy stating that opioids are essential for pain relief. In Armenia, a policy is in place, but a supplier still needs to be found.
“Uganda is a great success story,”
she continued. The initiative created a strategic health plan, added liquid morphine to the essential list, adopted new guidelines, and authorized prescription by nurses. Seventy-nine providers have been trained.
“We argue that no country should be allowed to enter the EU [European Union] unless they have opioids and a pain policy for cancer care. The solution is to identify champions at a country level and work with them. We can do this,” Foley said.
- Poveda A, Selle F, Hilpert F, et al. Weekly paclitaxel, pegylated liposomal doxorubicin or topotecan ± bevacizumab in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort in the GCIG AURELIA randomised phase III trial. Presented at: European Society for Medical Oncology 2012 Congress; September 30, 2012; Vienna, Austria. Abstract LBA26.
- van der Graaf W. Successful targeting of VEGFR in soft tissue sarcomas. Presented at: European Society for Medical Oncology 2012 Congress; September 30, 2012; Vienna, Austria.
- van der Graaf WTA, Judson I, Verweij J, et al. Results of a randomised phase III trial (EORTC 62012) of single agent doxorubicin versus doxorubicin plus ifosfamide as first line chemotherapy for patients with advanced or metastatic soft tissue sarcoma: a survival study by the EORTC Soft Tissue and Bone Sarcoma Group. Presented at: European Society for Medical Oncology 2012 Congress; October 1, 2012; Vienna, Austria. Abstract LBA7.
- Verma S, Miles D, Gianni L, et al. Updated overall survival results from EMILIA, a phase 3 study of trastuzumab emtansine (T-DM1) vs. capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC). Presented at: European Society for Medical Oncology Congress; October 1, 2012; Vienna, Austria. Abstract LBA12.
- Foley K. A global policy approach to freedom from cancer pain. Presented at: European Society for Medical Oncology 2012 Congress; September 29, 2012; Vienna, Austria.