PAN-EX supports neoadjuvant chemotherapy in high-risk rectal cancer

By Shreeya Nanda

Patients with high-risk, locally advanced rectal cancer could benefit from neoadjuvant chemotherapy before undergoing chemoradiotherapy, suggest the results of a pooled analysis.

The PAN-EX study, published in the Annals of Oncology, used individual patient data from the phase II EXPERT and EXPERT-C trials, which investigated the role of neoadjuvant chemotherapy followed by chemoradiotherapy in this patient population.

Among 269 patients in the intention-to-treat (ITT) population, 91.1% and 88.1% completed neoadjuvant chemotherapy and subsequent chemoradiotherapy, respectively.

During a median follow-up of 71.9 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates in the ITT population were a respective 66.4% and 73.3%.

And the team found that the magnetic resonance imaging tumour regression grade (mrTRG) after neoadjuvant chemotherapy and chemoradiotherapy correlated with survival outcomes.

Specifically, PFS was significantly better for patients who achieved complete or good (mrTRG1/2) and intermediate (mrTRG3) tumour regression after neoadjuvant chemotherapy than those with poor tumour regression (mrTRG4/5), with hazard ratios (HRs) of 0.18 and 0.47, respectively. However, OS was significantly improved only for mrTRG1/2 patients relative to those categorised as mrTRG4/5, with an HR of 0.23.

Similarly, survival outcomes after chemoradiotherapy were significantly better only for patients who achieved mrTRG1/2, with an HR of 0.37 for PFS and of 0.44 for OS compared with mrTRG4/5 patients.

These findings suggest that individuals who achieve intermediate tumour regression after neoadjuvant chemotherapy may be more likely to benefit from the use of sequential chemoradiotherapy than those who achieve complete or good or poor tumour regression, "who may have only a marginal incremental survival advantage", say the researchers.

However, the team urges caution in the interpretation of their findings owing to "the relatively small samples size and the design of PAN-EX (i.e., all patients received [chemoradiotherapy])".

David Cunningham, from The Royal Marsden NHS Foundation Trust Hospital in Sutton, UK, and fellow investigators conclude that this analysis confirms that administration of neoadjuvant chemotherapy before chemoradiotherapy could be a potential strategy for rectal cancer patients with high-risk, locally advanced disease.

But the lack of a standard chemoradiotherapy control group limits the wider applicability of their results and randomised phase III trials are needed to provide a definitive conclusion on the role of neoadjuvant chemoradiotherapy in this population, they add.

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