SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – Colorectal cancer originating on the right side carries a higher risk of recurrence or death after adjuvant oxaliplatin-based chemotherapy, suggests a new analysis of data from the SCOT (Short Course Oncology Therapy) trial. But patients with right-sided disease fare about the same whether given the usual 6 months of chemotherapy or half that.

“It’s becoming clear that right-sided tumors are different from left-sided tumors,” commented first author Mark P. Saunders, MD, PhD , a consultant oncologist at the Christie NHS Foundation Trust, Manchester, England. A large meta-analysis showed that early right-sided tumors were associated with poorer overall survival (JAMA Oncol. 2016 Oct 27. doi: 10.1001/jamaoncol.2016.4227 ), but it remains unclear at what point(s) in the course of disease and its treatment sidedness is exerting its influence.

In SCOT , a multinational phase 3 noninferiority trial, patients with resected high-risk stage II or stage III colorectal cancer were randomized to 3 months versus 6 months of adjuvant chemotherapy (CAPOX [capecitabine and oxaliplatin] or FOLFOX [folinic acid, fluorouracil, and oxaliplatin] according to patient and physician choice). Main results showed that the short-duration chemotherapy was not inferior to the standard-duration chemotherapy in terms of disease-free survival (J Clin Oncol. 2017;35:suppl; abstract 3502 ).

In the new analysis, the investigators assessed the impact of tumor sidedness among 3,219 patients having that information. Results reported at the 2018 GI Cancers Symposium showed that those with right-sided tumors (up to but not including the splenic flexure) had a 40% higher risk of disease-free survival events. However, there was no significant difference by side according to duration of chemotherapy.

“This is the first trial to show that unselected patients with right-sided tumors have worse disease-free survival, compared to those with left-sided tumors,” Dr. Saunders summarized. This finding suggests that greater recurrence risk is driving the poorer overall survival of the former.

“Tumor sidedness did not impact on the 3 months versus 6 months comparison in SCOT,” he further noted. “I suppose it would have fitted a very nice story that the rights did worse, and therefore, 6 months was better [for this group]. We didn’t show that in this trial here, so I don’t think we can say that at all. We still have to say that the outcome of the SCOT trial was that 3 months is noninferior to 6 months.”

Findings in context

“This study was interesting, but I feel that we still need more data coming from the main study,” session chair Michael J. Hall, MD, MS , a medical oncologist at the Fox Chase Cancer Center, Philadelphia, said in an interview. “It’s important to let us know that adjuvant chemotherapy appears to be beneficial, regardless of side, but there are still some other important questions.”

More detail on the difference by side according to chemotherapy duration and according to regimen (because recent data suggest CAPOX may have an edge over FOLFOX) could help tailor treatment, he proposed. For example, it is possible that patients with right-sided tumors will fare better if given 6 months of the CAPOX regimen.

“We need to know the interactions, which therapy is going to be better for which tumor location,” Dr. Hall concluded. “Dr. Saunders didn’t quite have those data to tell us that. But I think when the data completely mature, it will be super-duper interesting.”

Study details

The majority of the 3,219 patients studied, 63%, had tumors originating on the left side (splenic flexure or distally), according to data reported at the symposium, sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

Compared with patients who had left-sided tumors, those with right-sided tumors (including any in the transverse colon) were older (median, 66 vs. 64 years; P less than .001), less often male (53% vs. 66%; P less than .001), more often had T4 stage (41% vs. 24%; P less than .001), and less often had stage II disease (17% vs. 21%; P =.001).

Patients with right-sided tumors had poorer 3-year disease-free survival (73% vs. 80%; hazard ratio, 1.401; P less than .0001), reported Dr. Saunders. This association weakened slightly after adjustment for T stage and N stage (HR, 1.215; P = .009).

However, benefit of 3 months versus 6 months of chemotherapy was similar whether patients had right-sided tumors (HR, 1.049) or left-sided tumors (HR, 0.910), with no statistically significant heterogeneity between these groups (P =.327).

A large translational substudy, Trans SCOT, is looking at various biomarkers such as microsatellite instability and mutations, and may shed more light on the mechanisms driving the different outcomes for right- and left-sided colorectal cancer, according to Dr. Saunders.

However, even when starting with more than 3,000 patients, drilling down by tumor sidedness and then further by characteristics such as molecular features (or regimen, overall stage, or T and N components) may result in underpowered analyses, he cautioned.

Dr. Saunders disclosed that he received honoraria from and has a consulting or advisory role with Amgen, Merck, Roche, and Servier.

SOURCE: Saunders MP et al. 2018 Gastrointestinal Cancers Symposium, Abstract 558 .


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