Health

Neoadjuvant Regimen Tops Standard for Locally Advanced Rectal Cancer

Adding neoadjuvant chemotherapy to preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer led to better disease-free survival (DFS) and less toxicity as compared with a standard regimen of neoadjuvant CRT and adjuvant therapy, a randomized trial showed.

DFS at 3 years improved from 69% with standard treatment to 76% with neoadjuvant chemotherapy followed by chemoradiotherapy (CRT) before surgery. Grade 3/4 adverse events (AEs) associated with adjuvant chemotherapy occurred substantially less often in patients who received neoadjuvant chemotherapy, as reported in Lancet Oncology.

“The significantly improved disease-free survival in the neoadjuvant chemotherapy group and the reduced toxicity indicate that the perioperative approach is more efficient and better tolerated than adjuvant chemotherapy is. Therefore, these results could change clinical practice,” concluded Thierry Conroy, MD, of the Cancer Institute of Lorraine in France, and colleagues.

The results, combined with those of the phase III RAPIDO trial, support the clinical view that the era of all-neoadjuvant therapy has arrived, according to the authors of an accompanying editorial. However, the impact on clinical practice may differ according to current standards at different medical centers.

“Taking both trials together, the evidence for the superiority of neoadjuvant over adjuvant chemotherapy is strong,” stated Joanna Socha, MD, and Krzysztof Bujko, MD, both of the Military Institute of Medicine in Warsaw, Poland. “Therefore, in the institutions where adjuvant chemotherapy has been the standard of care to date, the answer to the question of whether or not we are already in the era of total neoadjuvant treatment for rectal cancer is: yes, we are. However, in those institutions where adjuvant chemotherapy has not been the standard of care, the answer might be negative.”

The practice of avoiding adjuvant chemotherapy has support from a meta-analysis that failed to show a benefit in overall survival (OS) or DFS with adjuvant chemotherapy versus observation.

“Unequivocal evidence to inform practice change could be provided by future reports of phase III trials showing organ preservation in a high proportion of patients or an improvement in overall survival after total neoadjuvant treatment,” Socha and Bujko concluded.

For patients with locally advanced rectal cancer (stages T3, T4, or N+), the current standard of care consists of chemoradiotherapy followed by total mesorectal excision (TME), Conroy and colleagues noted. The approach provides good local disease control, but distant metastasis remains a problem.

Adjuvant chemotherapy after preoperative CRT remains controversial as it has not shown an improvement in OS, in part because of poor compliance with treatment, the authors continued. Phase II trials of total neoadjuvant therapy have yielded promising results, but potentially practice-changing data from phase III trials are lacking.

To address the need for phase III data, investigators at 35 French centers conducted the UNICANCER-PRODIGE 23 trial to compare total neoadjuvant therapy with standard therapy. All patients received preoperative CRT, followed by surgery (TME strongly encouraged) and adjuvant chemotherapy (3 months in the neoadjuvant arm and 6 months in the control arm). Patients randomized to the neoadjuvant arm received modified FOLFIRINOX6 prior to CRT.

The primary endpoint was 3-year DFS, and secondary endpoints included OS, metastasis-free survival (MFS), and cancer-specific survival (CSS). Data analysis comprised 461 randomized patients with newly diagnosed, biopsy-proven, locally advanced rectal cancer.

After a median follow-up of 46.5 months, the DFS hazard at 3 years was reduced by 31% in the neoadjuvant group (95% CI 0.49-0.97, P=0.034). OS at 3 years did not differ significantly (91% with neoadjuvant therapy vs 88%), nor did 3-year CSS (92% vs 89%). MFS at 3 years was significantly improved in the neoadjuvant group (79% vs 72%, P=0.017).

Significantly more grade 3/4 AEs associated with adjuvant chemotherapy occurred in the control arm (79% vs 45%, P<0.0001). Grade 3/4 neutropenia, thrombocytopenia, and lymphopenia all occurred significantly more often in the patients who received 6 months of adjuvant therapy. In general, nonhematologic AEs occurred more often in the control group, including all-grade and grade 3/4 AEs.

  • Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

The study was supported by Institut National du Cancer, Ligue Nationale Contre le Cancer, and R&D Unicancer.

Conroy disclosed no relevant relationships with industry. Co-authors disclosed multiple relevant relationships with industry and others.

Socha and Bujko disclosed no relevant relationships with industry.

Source link

Leave a Reply

Your email address will not be published. Required fields are marked *

Back to top button

Ad Block Detected

Welcome to Mediexpose, Please support our journalism by allowing ads. With support from readers like you, we can continue to deliver the best. You can support us free by simply allowing ads.