Neoadjuvant therapy shows promise in improving outcomes in colorectal cancer

Collating the findings of several clinical trials, experts have recently shown the potential of neoadjuvant therapies in improving certain outcomes among patients with colorectal cancer at the 1st Congress of the International Society for the Study of Pleura and Peritoneum (ISSPP 2019) in Singapore.

Dr Chee Cheng Ean, senior consultant for medical oncology at the National University Cancer Institute, Singapore (NCIS), presented updates on recent trials on colorectal cancer.

Total neoadjuvant therapy feasible, safe

Being highlighted was a phase III study in Poland that sought to determine whether preoperative short-course radiotherapy and consolidation chemotherapy (CCT) were better than chemoradiation in patients with clinical (c)T4 or fixed cT3 rectal adenocarcinoma.

Results showed nonsignificant difference in overall survival (OS) between the two treatment arms (HR, 0.90, 95 percent CI, 0.70–1.15; p=0.38), but the difference in early OS favouring short-course/CCT previously reported was seen (9 percent at 3 years, 95 percent CI, 0.5–17 percent). This, however, did not persist at 8 years, with an OS of 49 percent in both arms. [Ann Oncol 2019;doi:10.1093/annonc/mdz18]

“Total neoadjuvant therapy [in rectal cancer] is feasible and safe,” said Chee, adding that its adoption as standard clinical practice will be determined by its toxicity profile, patients’ quality of life and shorter overall treatment time.

Neoadjuvant therapies for colon cancer

For colon cancer, Chee discussed on findings from FOxTROT, an international randomized controlled trial that evaluated the efficacy and safety of neoadjuvant chemotherapy (NAC) in colon cancer and included a total of 1,052 patients (median age 65 years) from 85 centres in UK, Denmark, and Sweden.

FOxTROT sought to answer the following question: Does NAC improve cure rates in colon cancer?

Results revealed that although NAC did not meet the primary outcome of a significant reduction in recurrence at 2 years (13.6 percent in the NAC group vs 17.2 percent in the control group; hazard ratio [HR], 0.75, 95 percent confidence interval [CI], 0.55–1.04; p=0.08), it was well tolerated and safe, with no increase in perioperative morbidity. [J Clin Oncol 2019;37:3504-3504]

In addition, a trend toward fewer serious postoperative complications compared with controls was observed (eg, 4.7 percent vs 7.4 percent rate of anastomotic leak or intra-abdominal abscess; 4.3 percent vs 7.1 percent rate of complications requiring further surgery, and 12 percent vs 14 percent rate of complications prolonging postoperative stay).

There was evidence of histological regression in more than half of the patients (59 percent) after NAC, which resulted in significant histological downstaging and a halving of the incomplete resection rate. An improvement in 2-year failure rate (HR, 0.77) was also seen, albeit statistically nonsignificant (p=0.11).

“NAC for early-stage colon cancer appears safe, but improved tumour regression and downstaging did not translate to [a] reduction in recurrence,” Chee said.

In another study (phase II NICHE) involving patients with early-stage colon cancer, short-term neoadjuvant ipilimumab plus nivolumab led to major pathological responses in 100 percent of dMMR tumours without compromising surgery. [ESMO 2018, abstract LBA37_PR]

“Short course neoadjuvant immunotherapy appears promising for dMMR tumours but warrants independent validation,” Chee said.

How about immunotherapy for gastric cancer?

Dr Yong Wei Peng, associate director and senior consultant from the Department of Haematology-Oncology at the NCIS, also shared some insights from the KEYNOTE-062 study on the use of first-line pembrolizumab in patients with programmed death-ligand 1 (PD-L1) combined positive score ≥1 (CPS ≥1) advanced gastric or gastro-oesophageal junction (G/GEJ) adenocarcinoma.

In patients with gastric cancer, first-line pembrolizumab was on a par with chemotherapy in terms of overall survival (OS), and it demonstrated significantly improved OS in those with CPS ≥10. [ESMO 2019, abstract LBA44]

However, pembrolizumab plus chemotherapy neither showed superior OS or progression-free survival in patients with CPS ≥1 nor OS in those with CPS ≥10 compared with chemotherapy alone. Additionally, health-related quality of life was comparable between pembrolizumab and chemotherapy in the first-line treatment of advanced G/GEJ adenocarcinoma. [ESMO 2019, abstract LBA45]

“Pembrolizumab with or without chemotherapy is not yet ready for prime time in first-line gastric cancer,” Yong said.

This was concurred upon by Dr Matthew Ng, senior consultant at the National Cancer Centre Singapore, who presented findings of another study by Shitara and colleagues, which focused this time on the use of pembrolizumab vs paclitaxel as second-line treatment for patients with G/GEJ cancer.

Compared with paclitaxel, second-line pembrolizumab did not significantly improve OS in patients with PD-L1 CPS ≥1 advanced G/GEJ cancer. However, pembrolizumab demonstrated a better safety profile than paclitaxel. [Lancet 2018;392:123-133]