This article is more than 5 years old. Information may no longer be current.
‘Port-alisib’ and ‘reach-out-to-me-mab’: A novel combination extends OS in a range of cancer types
Important new data from the ASCO Annual Meeting
Before you Google this combination to figure out how you missed the presentation at the ASCO Annual Meeting, please read on. I do not want you to waste your time!
This year’s ASCO was pretty remarkable. I cannot remember a recent meeting that included so much practice-changing data.
Reports from ASCO have been full of new advances, Twitter has had a constant stream of new data transmitted in real time from oral sessions, and the popular media have become very engaged. Even The Washington Post published a piece on the last day of the meeting titled “Eight things doctors are buzzing about.”
Not surprisingly, the article cites combination checkpoint inhibitors, chimeric antigen receptor T cells and concerns about financial toxicity among these.
Landmark studies
There is no doubt that landmark studies have been presented this year.
The common theme has been the continued ascendency of targeted treatments that extend DFS and OS in many tumor types. It would take more than the word limit of this editorial to list them all, but some are particularly noteworthy.
Larotrectinib (LOXO-101, Loxo Oncology) — a selective pan-tropomyosin receptor kinase (TRK) inhibitor — demonstrated efficacy across a range of 17 pediatric and adult TRK–fusion cancers (see article). Researchers reported a 76% overall response rate among 55 patients, who ranged in age from 0.3 to 75 years.
Although these were mostly rare cancers — rates of TRK fusion in common cancers are only between 0.2% and 3% — these results bring the concept of “tumor-agnostic” therapeutics a step closer to the clinic. As long as surgery remains the primary treatment modality for most cancers, it is hard to envision the decline of organ-based oncology practice, but this is a significant, early step down that path.
Combination checkpoint inhibition continues to show sometimes stunning activity in what have generally been thought to be hopeless situations.
I was particularly struck by the results of the CheckMate 204 and ABC studies, which combined ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (Opdivo, Bristol-Myers Squibb) for the treatment of central nervous system metastases from melanoma (see article). Both studies showed overall response rates in excess of 40% with meaningful prolongation of PFS.
The list of similarly remarkable results includes olaparib (Lynparza, AstraZeneca) in BRCA–mutated breast cancer, and the use of abiraterone acetate (Zytiga; Janssen) in metastatic prostate cancer (see article). Again, these studies are set to change the standard of care.
Price of progress
Attention to the cost of these and many other new agents seemed less focused than in previous years.
Although at least one session addressed financial toxicity of cancer treatment, overall the value proposition took more of a back seat.
I was struck by the multitude of banners and billboards advertising many of these drugs at the airport, lining the highways to Chicago and in the city. I also was surprised — and a little disappointed — to see the corporate stands in the exhibit hall seemed larger and flashier than they have for many years. This is a personal impression only — I have no data to support this — but it brings back memories of some of the excesses of the late 1990s and early 2000s.
It is no surprise that, as oncologists, many of us get the biggest “buzz” from seeing improvements in outcome from new targeted agents. This fulfils our need for validation of the scientific principles at the heart of oncology practice, as well as genuine desire to improve the lives of our patients. We all understand the need for value-based practice, but the allure of new treatments with promising results sometimes obscures objectivity and we run the risk of ignoring the very marginal benefits some of these drugs bring.
With that in mind, a comment Harold J. Bernstein, MD, PhD, FASCO, made at the press conference ahead of the plenary session is highly relevant (see perspective).
Discussing the results of a study by Ethan M. Basch, MD, MSc, FASCO, and colleagues, HemOnc Today quoted Bernstein as saying: “If a drug had a survival advantage of this magnitude, it would be retail priced at hundreds of thousands of dollars.”
Monika K. Krzyzanowska, MD, MPH, discussant of this abstract during the plenary session, pointed out that the FDA approved seven drugs for advanced solid tumors in 2016, only one of which provided a survival advantage greater than that reported in the study by Basch and colleagues.
This is remarkable because the “novel” intervention was not a drug, but an application of an online reporting tool for patients with cancer, which improved median OS by 5 months compared with a control group.
The study, now published in JAMA, included 766 patients with metastatic solid cancers. Researchers randomly assigned them to a patient-reported outcomes (PRO) intervention — who self-reported symptoms, selected from the NCI’s Common Terminology Criteria for Adverse Events, via an online portal — or to usual care.
Change in health-related quality of life at 6 months — the study’s primary endpoint — improved from 18% in the control arm to 34% in the PRO arm. With median follow up now at 7 years, the median OS was 31.2 months in the PRO group compared with 26 months in the control group.
Patient-reported outcomes
The Basch study is not the first to demonstrate the utility of remote PRO monitoring for improving quality of life in patients with cancer. My colleague, Kathi Mooney, PhD, RN, FAAN, and her team at University of Utah have reported on automated home monitoring of symptoms to improve patient quality of life and safety.
The improvement in OS in the Basch study is truly remarkable. The researchers hypothesize that this improvement may reflect early responsiveness to patients’ symptoms — nurses responded to alerts of new symptoms 77% of the time — providing real-time interventions, including supportive medications, dose modifications of chemotherapy and referrals to other providers.
In addition, patients in the PRO group stayed on chemotherapy for longer than those assigned usual care — another potential explanation for the better outcome. Whatever the reasons, if these data are confirmed in subsequent studies, they represent a practice-changing finding.
I can only speculate on how ASCO attendees viewed these data in the context of the other practice-changing findings this year.
I am pretty confident many of us left the meeting thinking about which new drugs we will be introducing into our practice, but I wonder how many of us left with definite plans to introduce a patient portal for symptom reporting — one of the most high-value interventions that improves OS at relatively low cost.
The point eloquently made by Bernstein — and much less elegantly in my title for this editorial — is that we seem to be more excited by high-tech than low-tech interventions. The results of this study suggest that checking in on our patients may be as, or more, effective in improving outcomes than checkpoint inhibitors!
References:
Basch EM, et al. JAMA. 2017;doi:10.101/jama.2017.7156.
Mooney K, et al. Cancer Med. 2017;doi:10.1002/cam4.1002.
The following were presented at ASCO Annual Meeting; June 2-6, 2017; Chicago:
Hyman DM, et al. Abstract LBA2501.
Tawbi HA-H, et al. Abstract 9507.
Long G, et al. Abstract 9508.
Robson ME, et al. Abstract LBA4.
For more information:
John Sweetenham, MD, FRCP, FACP, is HemOnc Today’s Chief Medical Editor for Hematology. He also is senior director of clinical affairs and executive medical director of Huntsman Cancer Institute at University of Utah. He can be reached at john.sweetenham@hci.utah.edu.
Disclosure: Sweetenham reports no relevant financial disclosures.