Conference Coverage

Neoadjuvant mFOLFIRINOX improves DFS, OS effect uncertain



Adding neoadjuvant chemotherapy to standard treatment of locally advanced rectal cancer more than doubled the pathologic complete response rate and significantly improved 3-year disease-free survival (DFS) in a multicenter, phase 3 trial.

The pathologic complete response rate was 12.1% in the standard therapy arm and 27.8% with the addition of neoadjuvant chemotherapy – modified FOLFIRINOX (oxaliplatin, irinotecan, folinic acid, and 5-fluorouracil). The 3-year DFS rates were 68.5% and 75.7%, respectively.

It’s not clear if the response and DFS benefits of modified FOLFIRINOX will translate to improved overall survival (OS). Nevertheless, neoadjuvant therapy with modified FOLFIRINOX “should now be considered as a new option” for T3-T4 rectal cancer, said investigator Christophe Borg, MD, PhD, of the University of Besancon (France).

Dr. Borg presented this research at the European Society for Medical Oncology Virtual Congress 2020.

Study discussant David Sebag-Montefiore, MBBS, of the University of Leeds (England), was more cautious about these findings. Although the results were “clear” in this trial, “we have not seen any overall survival data,” Dr. Sebag-Montefiore stressed.

Study details

In explaining the trial, dubbed PRODIGE 23, Dr. Borg noted that local recurrence is minimal with modern standard treatment – chemoradiation followed by total mesorectal excision (TME) – but distant metastases occur in up to 30% of patients and remain a significant problem despite years of research. Adjuvant chemotherapy after surgery might help, but it “is still not proven” to reduce the risk, so compliance is poor, Dr. Borg said.

He and his colleagues conducted the PRODIGE 23 trial to see if neoadjuvant chemotherapy could reduce the risk of metastases.

The study enrolled 461 patients, 18-75 years old, with cT3-4 rectal cancer. Patients were randomized to receive:

  • Standard therapy, consisting of chemoradiation (50.4 gy/5 weeks plus capecitabine), followed 7 weeks later by TME, then 6 months of adjuvant chemotherapy with FOLFOX (folinic acid, fluorouracil, and oxaliplatin) or XELOX (capecitabine and oxaliplatin, also known as CAPOX).
  • Six cycles of modified FOLFIRINOX, followed by chemoradiation (50.4 gy/5 weeks plus capecitabine), TME, and FOLFOX/XELOX adjuvant therapy for 3 months instead of 6 months.

Overall, 119 patients in the standard therapy arm and 130 in the neoadjuvant arm completed their assigned protocol.


The median follow-up was 46.5 months. The 3-year DFS, the primary endpoint, was significantly higher in the neoadjuvant arm than in the standard therapy arm (75.7% vs. 68.5%; hazard ratio = 0.69; P = .034). This correlated with a significant improvement in 3-year metastasis-free survival (78.8% vs. 71.7%; HR = 0.64; P < .02).

The rate of palliative surgery was significantly higher in the standard therapy arm (3.7% vs. 0%; P = .007), but there were no significant differences in other surgical outcomes.

A difference in 60-day postoperative mortality favored neoadjuvant therapy (0% vs. 2.8%, P = .03).

Grade 3 or 4 adverse events during adjuvant therapy were less common when subjects had neoadjuvant chemotherapy (44.4% vs. 74.1%, P < .001).

Quality of life outcomes were similar between the treatment arms, except that men in the neoadjuvant arm were significantly less likely to suffer from impotence (P = .03).

Dr. Sebag-Montefiore said these findings are “very important,” but PRODIGE 23 is not “a practice-defining or practice-changing study,” especially without OS data.

He noted that the RAPIDO trial had similar outcomes with a different neoadjuvant regimen.

RAPIDO had a standard treatment arm with capecitabine-based chemoradiotherapy followed by TME and optional CAPOX/FOLFOX, and the experimental arm consisted of short-course radiotherapy followed by CAPOX/FOLFOX then TME. The experimental arm had superior 3-year disease-related treatment failure (30.4% vs. 23.7%, P = .019) but no better OS (89.1% vs. 88.8%, P = .59).

PRODIGE 23 was funded by the French National Cancer Institute and the French National League Against Cancer. Dr. Borg disclosed relationships with Roche, Servier, Pierre Fabre, and Merck Sharp & Dohme. Dr. Sebag-Montefiore didn’t have any disclosures.

[email protected]

SOURCE: Borg C et al. ESMO 2020. Abstract LBA21.

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