Timing of adjuvant chemotherapy initiation does not impact pancreatic cancer outcomes

Patients with pancreatic cancer who initiated chemotherapy more than 12 weeks following resection appeared to experience similar survival as patients who initiated chemotherapy earlier, according to the results of a retrospective study.

“Surgical resection followed by adjuvant therapy currently is considered to be the standard of care,” Katelin A. Mirkin, MD, resident in the department of surgery, Pennsylvania State University College of Medicine, and colleagues wrote. “However, to the best of our knowledge, little is known regarding the relationship between the timing of chemotherapy initiation and survival. The early initiation of chemotherapy has been associated with survival benefit in other cancer types, including colorectal and breast cancer.”

Adjuvant chemotherapy is typically initiated between 6 and 12 weeks following surgical resection. Although previous research has suggested that initiation within 20 days of surgery improves outcomes compared with later initiation, other research has shown no adverse effect of delaying chemotherapy initiation by as long as 12 weeks following surgery.

Because initiation within 20 days following surgery is not always feasible, Mirkin and colleagues sought to evaluate how survival benefit is impacted by delaying chemotherapy initiation by more than 12 weeks following surgery.

Researchers used the National Cancer Data Base to identify patients who had clinical American Joint Committee on Cancer stage I to stage III resected pancreatic carcinoma. Patients were grouped into three cohorts based on treatment: surgery alone (n = 6,706; median age, 69.06 years; 48.6% men), adjuvant chemotherapy within 12 weeks of surgery (n = 3,723; median age, 65.48 years; 51.1% men), and adjuvant chemotherapy after 12 weeks (n = 669; median age, 66.43 years; 50.7% men). The overall median time to imitation was 51 days in the earlier-treatment group and 104 days in the later-treatment group.

The earlier- and later-treatment cohorts appeared comparable with regard to clinical stage, surgical specifics — regional/positive nodes, margins and resection type — and pathologic stage, which indicated that advanced disease did not correlate with later initiation, according to the researchers. However, patients who initiated chemotherapy later tended to be older (66.4 years vs. 65.5 years; P = .027) and have more comorbidities (Charlson-Deyo comorbiditiy condition score of 2, 8.8% vs. 6.4%).

Median OS among patients who underwent surgery alone was 14.4 months. Compared with that group, survival was improved among patients who received adjuvant chemotherapy after 12 weeks (22 months; multivariate HR = 0.65; 95% CI, 0.62-0.68) or within 12 weeks (20.8 months; multivariate HR = 0.65; 95% CI, 0.59-0.72).

Overall, survival did not significantly differ between the early- and late-treatment cohorts. Further, analyses stratified by pathologic disease stage showed earlier initiation of chemotherapy did not improve survival outcomes for any stage of disease.

Additional subgroup analyses showed that the benefit of adjuvant chemotherapy persisted even when treatment was administered beyond the 12-week stratification point. For example, patients who received adjuvant chemotherapy within 4 weeks following surgery experienced a similar survival benefit (HR = 0.8; 95% CI, 0.73-0.88) as patients who initiated chemotherapy 20 to 24 weeks following surgery (HR = 0.75; 95% CI, 0.61-0.93).

Researchers acknowledged that chemotherapy may have been delayed in some patients due to postoperative complications or patient preference, but they were not able to account for these factors. Also, the data do not include information on the chemotherapy regimen used.

“The results confirmed prior findings that surgical resection with adjuvant chemotherapy offers the best chance for long-term survival,” Mirkin and colleagues wrote. “The data suggest that the initiation of adjuvant chemotherapy [after] 12 weeks provides a similar survival benefit in patients with resected pancreatic cancer compared with those with an earlier initiation. Thus, delayed chemotherapy should be offered when appropriate.” – by Nick Andrews