ASCO 2009: Oncology Research Round-up

May 29 - June 2, 2009; Orlando, Florida

Deborah Brauser; based on news reports by Zosia Chustecka, Roxanne Nelson, and Nick Mulcahy

June 19, 2009

TRANSCRIPT

INTRODUCTION

Voiceover: The temperatures and the topics were hot in Orlando, Florida, where the major theme was personalized care at the 2009 annual meeting of the American Society of Clinical Oncology (or ASCO). More than 30 thousand professionals from all over the world came to the Orange County Convention Center to learn about the latest developments, treatments, and procedures in oncology.

TOGA: Trastuzumab for Gastric Cancer

Voiceover: The conference's biggest news, hailed as practice changing by ASCO's outgoing president, was the TOGA trial of trastuzumab (or Herceptin) for patients with advanced gastric cancer. When trastuzumab was added to chemotherapy, these patients had a significantly longer overall survival rate compared to chemotherapy alone. Lead author Dr. Eric van Cutsem presented the findings.

van Cutsem: "In fact trastuzumab is the first targeted agent, the first biological to show a survival benefit in advanced gastric cancer. Up to now we were treating patients with a combination of 2-cytoxics and sometimes 3-cytotoxics. But trastuzumab is the first biological. Moreover, we have shown that trastuzumab reduces the risk of death by 26% when combined with a reference chemotherapy, translation of the hazard ratio of 0.74. And trastuzumab in combination with chemotherapy prolongs the median survival by 2.7 months, going up from 11.1 to 13.8 months."

Voiceover: Dr. Sonali Smith, who was not involved in the study, called the TOGA findings "promising for a poor prognosis group of patients."

Smith: "This is an extremely important study. It's a very well conducted study. It's a large study showing that for the minority of patients, only 20% of patients but still a significant minority of patients, this is the first non-cytotoxic therapy to have shown any kind of effectiveness. So I would consider that extremely promising and would agree that repeating the study in this situation is not helpful to patients. But I think it's an important stepping stone on which to continue to build."

Bevacizumab for Early-Stage Colon Cancer

Voiceover: In other news on the GI cancer front, there was a negative outcome from the eagerly awaited C-08 trial of bevacizumab (or Avastin). The trial randomized patients with stage 2 and stage 3 colon cancer to receive either standard chemotherapy or standard chemo plus a year of bevacizumab. This study attracted a lot of attention because bevacizumab has been successful in the setting of metastatic colon cancer and was expected to do equally well here. However, the results showed no significant benefit in this setting. Lead author Dr. Norman Wolmark explained his team's findings.

Wolmark: "The hope was because bevacizumab prolongs survival in advanced disease, that moving it into the adjuvant setting would save lives, would increase the cure rate. And the results alas did not show that. We did not see a statistically significant difference for adding bevacizumab to standard oxaliplatin-based chemotherapy."

"Now, having said that, is this a complete failure? And the answer to that is no because we saw a robust but transient benefit for bevacizumab during the 1 year that bevacizumab was administered. So it immediately leads to the question whether longer administrations of bevacizumab beyond 1 year would give us the hoped for result of significantly prolonging disease-free survival and leading to an increase in cure rate for patients with stage 2 and 3 colon cancer."

Voiceover: However, commentator Dr. Nicholas Petrelli said that these results show there is no role for bevacizumab in the adjuvant setting for early-stage colon cancer off protocol.

Petrelli: "So this is a negative trial. Now, what Dr. Wolmark also showed was in the first year of treatment, there was a separation of the curves where survival was statistically significant, leading one to theorize that perhaps bevacizumab should be given for a longer period of time. But I emphasize that's theory and that's something that would have to be shown in a prospective randomized trial. The bottom line in CO8 is that it was a negative trial."

Surgery Not Necessary for Colorectal Cancer

Voiceover: Another GI abstract attracting a lot of attention was a retrospective study showing that surgery to remove the primary tumor is not necessary for the majority of patients with metastatic colorectal cancer.

In fact, the study showed that 93% of patients never developed symptoms that required surgical intervention. Although removing the primary tumor was once standard treatment of care, lead author Dr. Philip Paty says that's not the case in today's "era of multi-drug chemotherapy."

Paty: "I think it's important to recognize that when you treat with upfront chemotherapy, all options are still on the table. If a patient does well, you can intervene surgically at a later time. But the fact is, among the 233 patients we studied, only 7% in the long run required surgical intervention. Two-thirds of those were for obstruction, one-third for perforation, and only 2 among those 16 patients died as a result of surgical intervention. So that represents 0.8% mortality for the entire population. That compares very favorably to what you'd expect if you'd operated on all 233 upfront where mortality ranges from 1% to 5%.

So we feel that the benefits of this approach are that you avoid surgery in the vast majority of patients. It's an unnecessary procedure. Chemotherapy is begun early and the risks and the costs of surgery are avoided. We think this should be adopted as a standard practice for this patient population."

Dr. Petrelli: "The implication for private practice is that you don't necessarily have to remove the primary colon or rectal cancer in patients who present asymptomatically with those primaries in the presence of unresectable disease. So surgeons should not rush in to take those primaries out."

Pemetrexed for NSCLC

Voiceover: Moving over to lung cancer, there was substantial interest in a study that showed increased overall survival of 3 to 5 months when pemetrexed (or Alimta) was used for maintenance therapy in patients with advanced non-small cell lung cancer.

In addition, this benefit was greater for patients with nonsquamous histology. Lead investigator Dr. Chandra Belani discussed the findings.

Belani: "In this randomized study, for the first time we have shown that there is a significant benefit both in progression-free survival and overall survival with the use of pemetrexed in the maintenance setting. And we've also shown that the therapy is well tolerated and it can be administered over a long duration of time without any significant accumulative toxicity. When we look at overall survival, the hazard ratio is 0.79. That is an overall 2.8-month difference in median survival. But the survival continues to be there throughout the curve as seen by the hazard ratio."

Personalized Vaccine for Follicular Lymphoma

Voiceover: There was also a lot of buzz about a personalized idiotype vaccine for follicular lymphoma that prolongs disease-free survival — with results that were 10 years in the making.

After maintaining a complete response for 6 months after induction chemotherapy, patients who then received the vaccine, known as BiovaxID, showed a 47% improvement in median progression-free survival, compared with those who received the control. Dr. Stephen Schuster explained the clinical implications of his team's findings.

Schuster: "The implications are that we have a new therapeutic agent with clinical activity that may be applicable for treatment of our patients. Other immunotherapies that are available, such as rituximab, are antibody based. This vaccine induces cellular immunity, that is tumor reactive T-cells as well as tumor reactive antibody. So it's a different or additional mechanism of action and seems to be something that could be added logically to our chemotherapy or immuno-chemotherapy regimens."

Dr. Smith: "Certainly this is a very exciting study to create a patient-specific vaccine, and I think really kind of prompts investigation as to how this study is different from the other large phase 3 randomized studies that have previously been done, and to also investigate where this might fit into the treatment options that are currently available for patients with follicular lymphoma."

PARP Inhibitor for Breast Cancer

Voiceover: In breast cancer news, an investigational PARP-1 inhibitor captured attention with results from its phase 2 trial. Combined with conventional chemotherapy, the PARP inhibitor — known as BSI-201 — improved survival by almost 4 months in women with metastatic triple-negative breast cancer compared with those receiving chemotherapy alone. Investigator Dr. Joyce O'Shaughnessy shared insights into the study she presented.

O'Shaughnessy: "Triple-negative breast cancers have a lot of this PARP enzyme. So if you inhibit it, the thought is that the chemotherapy will work a whole lot better and you might really help the patients. And that's what we found. The clinical benefit rate, which was the main endpoint of the trial, nearly tripled from about 21% up to 62%. The objective response rate did triple from 16% up to 48%. And then we looked at progression-free and overall survival, which were secondary endpoints. And there's a significant improvement, more than a doubling in progression-free survival and an improvement in overall survival from a median of 5.7 months with gemcitabine-carboplatin up to 9.2 months with the addition of the BSI-201."

Voiceover: Dr. Eric Winer, who was not involved in the study, called both the PARP inhibitor and these findings "very interesting."

Winer: “Over the past 5 years, there has been a great deal of discussion about triple-negative breast cancer and both we and our patients have been frustrated by the fact that we are left with largely chemotherapy alone and that there haven't been targeted agents. This, while still very preliminary, is one of the most exciting findings we've seen in a long time and of course it will need to be confirmed. But these are really very, very exciting results."

Follow-up for Micrometastases in Sentinel Lymph Node

Voiceover: Also in breast cancer, there were new data from a Dutch study showing that women who are found to have micrometastases in the sentinel lymph node should have follow-up treatment on additional axillary lymph nodes. This information could provide the tipping point for physicians not currently treating women for this stage of cancer.

Lead author Dr. Vivianne Tjan-Heijnen explained the results.

Tjan-Heijnen: "We observed that in patients with micrometastases who didn't receive further axillary treatment, an increased axillary recurrence rate occurred. It was 5% after 5 years and we were concerned about this incidence rate and looked at different parameters that might have influenced this result. Not only axillary treatment was important but also tumor size and histological grade. Within the group of patients with micrometastases, this rate remains too high. So we recommend that all patients with micrometastases receive further axillary treatments."

Voiceover: Commentator Dr. Julie Gralow, who serves on the ASCO Communications Committee, says that this study shows that micrometastases should not be ignored.

Gralow: "I think this is important. It helps us a bit in our struggle with the isolated tumor cell group, and I actually think it helps us with probably being a little more aggressive with the micrometastatic group. We might have gotten a little complacent and not treated it when we should have. We need to look at long-term results as opposed to just recurrences in a couple of years."

Prophylactics for Cetuximab and Panitumumab Rash

Voiceover: The severe rash that often occurs with cetuximab and panitumumab treatment is a signal that the drug is working. However, this rash is often bothersome for patients, causing some to stop therapy completely. A new study now shows that a prophylactic treatment — made up of a moisturizer, topical steroid, antibiotic, and sunscreen — can cut the incidence of this rash in half. Lead author Dr. Edith Mitchell presented the findings.

Mitchell: "The results of our study showed that prophylactically or preventively treating the patient prior to initiation of chemotherapy that included epidermal growth factor receptor inhibitors resulted in less toxicity for the patients. Less toxicity but also less systemic effects such as nausea, vomiting, and diarrhea. Also, there were fewer dose delays in the patients receiving the preemptive or prophylactic therapy."

Voiceover: Based on the findings, commentator Dr. Jennifer Obel says that she now plans to inform her own patients about this study and about the prophylactic option.

Obel: "This is a very simple and elegant study. Like we've learned from the management of the many common side effects of our chemotherapies, it's more effective to prevent them than try to treat them when they occur. At that point, our interventions may be less effective and our patients are already in distress. The panitumumab-associated skin rash can occur in over 90% of our patients. I'm a GI oncologist and I watch every day how my patients either refuse therapy, stop therapy, or receive a lower dose of the drug because of this disfiguring rash. I think this can represent a new standard of care for treatment of GI malignancy patients who are receiving these drugs."

Fertility Preservation Guidelines

Voiceover: For any physician treating cancer patients of child-bearing age, a recent survey of 613 oncologists show that many of them are not following ASCO guidelines when it comes to referring patients for fertility preservation discussions or distributing educational materials. Investigator Dr. Gwendolyn Quinn discussed the survey's findings.

Quinn: "What we found was that there were low rates of awareness of the ASCO guidelines. And while there were high rates of discussion, there were lower rates of referrals to a reproductive endocrinologist or fertility specialist. And since fertility preservation is an important quality-of-life issue for cancer patients of child-bearing age, it's important that we developed tools that help facilitate and improve this communication, this important quality-of-life issue between oncologists and cancer patients."

CLOSE

Voiceover: For full reports on these and other studies from ASCO's 2009 Annual Meeting, visit Medscape Oncology at oncology.medscape.com.

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