GORDON McVIE: My Key Takeaways from ASCO11

J. GORDON McVIE, MD, Chair of the Editorial Board of OT's UK Edition, is Senior Consultant to the European Institute of Oncology, Visiting Professor at Glasgow University, and Honorary Consultant in Medical Oncology at the Welsh Cancer Institute.CHICAGO—Melanoma, for the second consecutive year, led the billing at this year's ASCO Annual Meeting in terms of what's new. Last year it was ipilimumab in second-line treatment in melanoma; and this year was a randomized trial with ipilimumab and dacarbazine versus dacarbazine alone, with ipilimumab prolonging overall survival compared with use of single agent dacarbazine. It is interesting to wonder what's going to happen to dacarbazine in the treatment of melanoma, because the other big story around melanoma was vemurafenib, also known as PLX4032. It targets BRAF V600E, a mutation found in around half of melanoma patients, so it's a significant number of people who could benefit. The good news is that vemurafenib resulted in a 63% reduction in risk of death versus dacarbazine, as reported by Paul Chapman of Memorial Sloan Kettering Cancer Center, where they carried out a randomized Phase III trial. So now we have, in the space of two years, two drugs that really should be used upfront for the BRAF-mutated group of patients, so one would be tempted to go with the new targeted agent first. But for those patients who do not have a BRAF mutation, then obviously ipilimumab would be the drug of first choice. The questions now are: Can you combine these agents? Do you use them sequentially? Which one do you use first? Really exciting times for treatment of melanoma. Prostate Cancer Last year there was also quite a lot of excitement about prostate cancer and the move from hormone-resistant prostate cancers to “castration-resistant” because of the new drug abiraterone, a hormone agent. It is working in patients who have previously been called hormone-resistant—hence the change in terminology—and has held up over the last year, giving clear overall survival data in favor of abiraterone in patients who are castration-resistant with prostate cancer (15.8 months for those on abiraterone and prednisone vs 11.2 months for those on prednisone and placebo). So two bits of confirmatory data in well-organized, randomised Phase III trials. Ovarian Cancer: ‘BRCAness' Also last year there was quite a lot of excitement about olaparib, a PARP1 inhibitor. Now we have data on ovarian cancer patients who haven't necessarily got a BRCA1 or 2 mutation but have “BRCAness.” It looks from this data that olaparib does have considerably good activity and a not particularly damaging side effect pattern. The pathologists tell me that it's easy to diagnose histopathologically; you don't need to have a BRCA-like test. So olaparib in BRCA-like ovarian cancers is worthy of accelerated investigation, in my view. Rarer Cancers There were two or three sessions that highlighted rarer tumors: Children's cancers haven't been featured often in the highlights from ASCO, but this year there were a couple of really important highlights in my view. The first is a very nice study done by the European SIOP Neuroblastoma group, lead by Ruth Ladenstein at the University of Vienna. It looked at difficult-to-treat neuroblastoma patients—young children with neuroblastoma that has metastasized or has the wrong kind of pathology. Dr. Ladenstein and her team showed that the previously standard myeloablative cocktail, which was carboplatin, etoposide, and melphalan, is inferior to two old drugs from 40-plus years ago when I started—busulfan and melphalan. So the new standard treatment for myeloablation in children with nasty, aggressive neuroblastoma should be melphalan plus busulfan. Another Blast from the Past Another blast from the past saw high-dose methotrexate—surprisingly, for the first time in a randomized trial—against an escalating dose of methotrexate together with asparaginase for acute lymphocytic leukemia. This was a cocktail put together by Robert Capizzi at Yale some time ago, and a clear advantage was found for high-dose methotrexate in terms of time to relapse, and protection from CNS metastases, etc. Imatinib for GIST The second not so frequently reported cancer, due to its infrequent nature, is GIST (gastrointestinal stromal tumors). These only really came to be an entity thanks to the discovery that imatinib was active in this radioresistant, chemoresistant tumor. Imatinib, of course, was developed for chronic myeloid leukemia. Now we have a nice study for patients who were diagnosed early enough to have had an operation for their GIST; an adjuvant study of one year versus three years of imatinib clearly points to three years of imatinib being superior. Hematologic Malignancies In the hematological malignancies, there was one trial which I think is certainly worthy of note in relapsed/refractory multiple myeloma; testing a new antibody, elotuzumab, in combination with lenalidomide (the thalidomide analogue), and dexamethasone. It was a randomized Phase II study with a really healthy 82% response rate from a group of 98 patients. So that's good news with an antibody and lenalidomide and dexamethasone—three drugs with completely different side effect patterns, none of which could really be described as a classic cytotoxic drug. NSCLC, Breast Cancer There was not a great deal of news in the common cancers. A maintenance trial in non-small-cell lung cancer showed that pemetrexed added a couple of months when given in maintenance after front-line treatment with pemetrexed-cisplatin. But from 2+ months to 4+ months is sadly not a huge gain for patients with lung cancer. And a couple of studies in breast cancer stood out. A prevention study, with the aromatase inhibitor exemestane in 4,560 postmenopausal high-risk women, achieved a 65% reduction in the incidence of breast cancers compared with placebo. The only criticism in the corridors was, “well, there are not a lot of events yet,” and indeed the events were 11 breast cancers in the exemestane group versus 32 in the placebo group. Though these are small numbers, there is a significance because it was a very large study. We'll be watching for the follow-up data in the future. Exemestane has favourable comparisons with tamoxifen and the tamoxifen-lookalike drugs, as it does not result in the same sort of problems with thromboembolic disorder, and increased risk of uterine carcinomas. The second breast cancer story was a radiotherapy study, carried out by National Cancer Institute of Canada, into the control of the axilla—something that has fascinated senologists for a long time. This was a study of radiation therapy after local control by surgery, versus radiation to the breast and to the axilla. The patients randomized in this trial had high-risk breast cancers such as big tumors or any lymph-node positive results in the axilla. Randomization was straightforward: the usual quadrantectomy or surgical removal of tumor followed by the appropriate targeted therapy (hormonal, trastuzumab, chemo) and radiation just to the breast or breast and axilla. Unsurprisingly the study found an improvement in local regional recurrence in the locally and axillary irradiated group, but also a hint of a survival advantage as well, which was quite interesting. It supports some of the data already established by the European Organisation for Research and Treatment of Cancer (EORTC). The downside was a not huge, but significant, increase in lymphedema. So the Canadians will now be saying that this is the way we should be treating patients with advanced local disease. The last story was really another catch-up on ovarian cancer. Bevacizumab has been shown to improve progression-free survival in ovarian cancer patients in two big studies, ICON7 and GOG (Gynecologic Oncology Group). The ICON study reported an overall survival difference at this ASCO meeting. We have to wait for the GOG trial but should this support the ICON data, then it looks like—as with lung cancer and several other hematological disorders—maintenance is coming back into the picture. We'll be looking for the next set of trials investigating a variety of other antiangiogenesis drugs, not just in upfront treatment with cytotoxics of ovarian cancer, but also in maintenance. We'll be asking how long does that maintenance go on? Beyond a year, or forever? So, a good ASCO all round. Chicago is a great place to visit and to see all your old friends, but there was some good science too. The educational sessions were field-leading as always, and credit to George Sledge for leading a great meeting.

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