Katrina S. Pedersen, MD, MS
Katrina S. Pedersen, MD, MS, Assistant Professor of Medicine at Washington University School of Medicine, St. Louis, said while the results of the phase II -SEQUENCE trial1 are encouraging and the drugs are available to translate into the clinic without delay, phase III validation would be needed first. In the study, Spanish investigators showed superior outcomes in patients with metastatic pancreatic cancer who underwent a novel treatment strategy of nab-paclitaxel plus gemcitabine sequenced with modified FOLFOX (fluorouracil, leucovorin, oxaliplatin) vs standard therapy.
“The investigators of the SEQUENCE trial noted that some patients with metastatic pancreatic cancer become refractory to nab--paclitaxel/gemcitabine quite quickly. Thus, they proposed that these outcomes may be improved by switching, basically cycle by cycle, between the standard nab-paclitaxel/gemcitabine regimen and FOLFOX, throughout treatment,” she explained.
The study met its primary endpoint, with 55% of patients on the sequencing arm alive at 12 months, compared with 35% who received continuous nab-paclitaxel/gemcitabine. Median overall survival was improved by 3.5 months, and the risk of disease progression was reduced by almost 50%.
Clinical Implications
When asked whether the findings of this study were practice-changing, Dr. Pedersen said maybe. “The agents are already available, so anyone could technically apply these data in their clinic. However, this was a small phase II study, and we know phase III study success in pancreatic cancer is never guaranteed. We have been disappointed over and over, times 40,” she commented.
In addition, there could be value implications in incorporating this novel strategy. Dr. Pedersen estimated that switching from nab-paclitaxel/gemcitabine to FOLFOX may mitigate costs over time “if alternation leads to better disease control with fewer hospitalizations and fewer severe adverse events,” she suggested.
Dr. Pedersen questioned, however, whether nab-paclitaxel/gemcitabine alternating with FOLFIRINOX (fluorouracil, leucovorin, irinotecan, oxaliplatin) would produce even more benefit than alternating with FOLFOX. As she pointed out, FOLFIRINOX would have been the standard of care for patients with a good performance status who were young enough for it.
“The key takeaway is this is a very interesting study, but phase III validation is needed,” Dr. Pedersen concluded. “There will have to be some thoughtful decisions made in the phase III setting about the appropriate trial endpoints. What would convince everyone it is clinically beneficial to use four of the five approved drugs, all in the front line [compared to standard sequential therapy]?”
DISCLOSURE: Dr. Pedersen reported financial relationships with Array -BioPharma, Bayer, BeiGene, Nouscom, UpToDate, Novartis, Pfizer, Clinical Care Options, Taiho, GlaxoSmithKline, and WebMD.
REFERENCE
1. Carrato A, Pazo-Cid R, Macarulla T, et al: Sequential nab-paclitaxel/gemcitabine followed by modified FOLFOX for first-line metastatic pancreatic cancer: The SEQUENCE trial. 2022 ASCO Annual Meeting. Abstract 4022. Presented June 5, 2022.
