Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - Multinational Association of Supportive Care in Cancer (MASCC)

Rome, Italy / June 25-27, 2009

According to Dr. Richard Gralla, Chief, Division of Medical Oncology and Hematology, Monter Cancer Center, Lake Success, New York, “Three-quarters of our cancer patients should be able to achieve complete control of emesis with agents that are available today. Yet oncologists are often content to continue practicing the anti-emesis approaches of the 1990s with more than one-third of patients vomiting on the first day.” He added that recent studies have demonstrated that better results can be obtained by adding NK₁ receptor antagonists (RAs) such as aprepitant.

Quality of Life/CINV Control Essential in Cancer Care

Dr. Gralla confirmed that good supportive care is key to making excellent cancer care possible. He suggested that decreasing chemotherapy-induced nausea and vomiting (CINV) “preserves and improves quality of life [QoL], allowing us to administer drugs on an outpatient basis, so it is appropriate that we seek complete control of emesis for all patients. One goal should be to enhance the use of the most effective chemotherapeutic agents by providing superior supportive care. It is a shame to go to the second-best platinum agent in this disease because we are worried about emesis. Instead, we should be able to prevent the emesis in order to use the more effective anticancer drugs,” he told delegates.

Dr. Gralla noted that patients who graded their QoL before receiving chemotherapy and again three days following chemotherapy rated their QoL as equivalent at those two time points if they did not suffer CINV, but with any degree of CINV, their QoL dropped by one-third. He stated there are few things done in oncology which negatively affect QoL with such magnitude.

He noted, too, that fewer than half of patients given cisplatin or doxorubicin/cyclophosphamide (AC)-based chemotherapy achieve control of delayed emesis, but said another 20% receiving highly emetogenic chemotherapy could do better tomorrow by simply employing the drugs which are available today, following ASCO, MASCC and NCCN guidelines. The most important of those agents are dexamethasone, serotonin RAs and NK₁ RAs, he said, referring to the other classes of agents as being of minor importance in terms of reaching zero tolerance of vomiting. Dr. Gralla stated that the focus of current research must be to raise the level of control so that virtually no patient experiences vomiting or nausea, a goal that can be accomplished by enhancing current regimens. Once the control of vomiting is maximized, it is probable that the control of nausea will be more complex and other agents may be needed. He concluded that half of all patients experience vomiting and more have nausea because the most appropriate agents are not being used.

Study Findings

According to Dr. Bernardo Rapoport, Medical Oncology Centre of Rosebank, Johannesburg, South Africa, aprepitant added to ondansetron and dexamethasone has been proven effective against CINV in women with breast cancer receiving moderately emetogenic chemotherapy (MEC) consisting of an AC-based regimen and is recommended for that group of patients. However, he said, there is also a need to improve prevention of CINV in cancer patients receiving non-AC regimens, such as oxaliplatin and carboplatin, in which control is suboptimal.

His group investigated the ability of the NK₁ RA to prevent nausea and vomiting induced by a range of MEC agents. The study was conducted in 848 cancer patients with a variety of tumour types, including breast, colon, lung and ovary, throughout the acute and delayed phases after initiation of chemotherapy with a variety of MEC agents. These included oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin cyclophosphamide or cytarabine. Of the study group, 77% were women and 52% received non-AC-based regimens. The primary efficacy end point was the proportion of patients who experienced no vomiting during the 120 hours post-chemotherapy. The key secondary end point was the overall complete response (no emetic episodes and no administration of rescue therapy) during the same post-chemotherapy timeframe.

Dr. Rapoport reported that among patients receiving non-AC-based chemotherapy, significantly more in the aprepitant-containing regimen group reported no vomiting in all phases compared to those who were given ondansetron and dexamethasone, only, as control medication (overall phase, 83.2% vs. 71.3%; acute phase, 96.5% vs. 91.6%; delayed phase, 84.5% vs. 73.9%) and complete response in all phases (overall phase, 73.9% vs. 65.5%; acute phase, 93.4% vs. 88.1%; delayed phase, 76.1% vs. 69.0%). Among patients in the cohort receiving AC-based chemotherapy, more in the aprepitant group reported no vomiting compared to control patients in the overall, acute and delayed phases (68.3% vs. 52.9%; 86.9% vs. 76.0%; 70.4% vs. 59.8%), respectively.

For the primary efficacy end point of no vomiting, he said the absolute improvement was 14% in favour of aprepitant over control medication in the overall phase (days 1 to 5), 8% in the acute phase and 11% in the delayed phase, with all the P values being statistically significant, so the study met the primary end point, he said. Complete response, defined as no vomiting and no rescue medication, was also positive, with a 13% absolute improvement (acute phase, 9%; delayed phase, 10%) when aprepitant was added to the double therapy control protocol, he noted.

“Similar results were observed in patients receiving AC-based therapy,” Dr. Rapoport added. “There was a 15% overall improvement in the no vomiting primary end point overall. The difference in side effects did not differ significantly between the two groups.” He concluded that the aprepitant-containing regimen significantly improved the prevention of CINV among patients with a broad range of different tumour types receiving a variety of AC- and non-AC-based regimens.

As reported by Dr. David Warr, Division of Oncology, Princess Margaret Hospital, Toronto, Ontario, pivotal aprepitant studies with high-dose cisplatin demonstrated an absolute 20% improvement in emesis over the first five days following chemotherapy, with a smaller improvement in nausea. In the breast cancer study using an AC regimen in which Dr. Warr participated, there was an absolute 17% improvement in vomiting over the first five days. On the basis of those results, triple therapy with a 5-HT₃ RA, the NK₁ RA and dexamethasone became the new standard for cisplatin and MEC as well as AC-based chemotherapy.

“Nevertheless,” observed Dr. Warr, “aprepitant has not been used as widely as one might expect in North America for a standard-of-care medication. Overall, the usage rate across 83 practices was just over 30% in a survey. Although that number has increased somewhat, there remains a substantial number of practices in which no patients receive a NK₁ RA. That is because physicians may still underestimate the problem of emesis even when faced with data to the contrary.” He continued, “For example, the authors of a study of patients receiving AC chemotherapy with a 5-HT₃ RA and dexamethasone for CINV concluded that the therapy was ‘reasonably well tolerated,’ even though the emesis rate was basically identical and nausea rate actually higher than in similar clinical trials using the same definitions. In the acute phase alone, 25% of patients vomited and by day 5, 59% of them were still reporting nausea which is what patients in our breast cancer study with triple therapy had for the entire delayed phase,” he said.

He also presented a re-analysis of the aprepitant study in AC-type chemotherapy examining combinations of CINV prognostic factors. His analysis failed to identify a low-risk group of any meaningful size.

Summary

Researchers here this week concluded that enhancement of current regimens can lead to minimizing vomiting in many patients. Since control of vomiting exceeds the control of nausea, which may be a more complex problem, it can be expected that some degree of nausea will remain, but adding agents affecting additional pathways should lead to less nausea as well. The addition of aprepitant to an antiemetic regimen results in significantly improved prevention of CINV in patients receiving a broad range of AC- and non-AC-based MEC regimens.