Do Oncologists Change Practice Based on Inadequate Evidence?

Dr Steensma commented that while it’s “uncommon” for a poster to be practice changing, there are certainly oral presentations that are “clunkers” and posters that are “very good.”

The danger with changing practice on the basis of the findings from a meeting abstract — even one supported by an oral presentation — is that readers may not have the full, unbiased picture of the science supporting any claims made. “You are at the mercy of the speaker deciding what you should, or should not be, seeing,” explained Dr Gyawali.

“At conferences, every drug seems to be a game changer, or a paradigm shift, or a breakthrough, or practice changing,” said Dr Knopf. “It makes sense to wait until the dust settles a little bit, and you can take a rational approach to it.”

Furthermore, the research reported at medical meetings does not always hold up when it’s time to publish the data in a journal. For example, the results of the TOPACIO trial initially showed clinical activity for niraparib plus pembrolizumab regardless of BCRA mutational status in patients with triple-negative breast cancer, but then, in the journal article, the researchers concluded that the activity of this drug combination appeared to be limited to BRCA-mutated disease.^2,3

So, then, why do some oncologists act so quickly on what they think could potentially be practice-changing study findings?

One reason, explained Dr Steensma, is the desire to balance waiting too long to implement a change if the data are convincing, with not making changes too early. “That’s really the crux of the matter,” he said. “When is there enough evidence?”

A related reason likely spurring clinicians to adopt new prescribing patterns based on early evidence is the length of time it takes to acquire more data in the form of a published journal article. In fact, Dr Gyawali asserted, oncologists changing their practices on the basis of abstracts alone is not the real problem. “The problem is that we are allowing abstracts to be presented without asking for a deadline for publication of the paper.”

Although some high-impact studies are accompanied by the simultaneous publication of a journal article, it’s not uncommon for months to pass between when findings are first presented and when they are eventually published. “Our patients have needs that can’t always wait that additional 6 [months], 9 months, a year for a paper to be published,” emphasized Dr Steensma.

For example, the KEYNOTE-042 trial results were presented during the plenary session at ASCO in June 2018, providing support for first-line use of pembrolizumab monotherapy in lung cancer — yet the journal article on this topic did not appear until April 2019, and the overall conclusions remained the same.^4,5

“If authors have data that they believe are potentially practice changing,” said Dr Prowell, “then it’s really the responsibility of those investigators, as well as the responsibility of the journal and the peer reviewers for that journal, to treat publication of those data as a priority for clinical practice.”

References

1. DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17.
2. Vinayak S, Tolaney SM, Schwartzberg LS, et al. TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial. J Clin Oncol. 36(no. 15_suppl):1011-1011.
3. Vinayak S, Tolaney SM, Schwartzberg L, et al. Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer [published online June 13, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.1029
4. Lopes G, Wu Y-L, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. J Clin Oncol. 36(18_suppl):LBA4.
5. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819-1830.