Refinement of surgical treatment has been declared the clinical cancer advance of the year by the American Society of Clinical Oncology (ASCO) in its annual report.
Recent success with more effective cancer therapies has changed the role of cancer surgery, sometimes reducing the need for it, in particular in the treatment of melanoma as well as pancreatic and kidney cancers, the report notes.
"Surgery has played a fundamental role in cancer treatment," said Howard Burris, MD, ASCO president. He noted that historically, it was the only treatment available for many cancers.
"The explosion in systemic therapies since then has resulted in significant changes to when and how surgery is performed to treat cancer," he said.
ASCO's annual report on progress against cancer, issued for the 15th consecutive year, was published online February 4 in the Journal of Clinical Oncology.
It lists numerous clinical advances in the treatment of cancer that were made from October 2018 to September 2019, but highlights the following studies as "some of this year's most impressive research successes." These studies show how systemic therapies have reduced the amount of surgery needed, or have even eliminated the need for it in some instances, while allowing patients to become eligible for surgery if needed.
Neoadjuvant Therapies in Melanoma
Two clinical trials show how the use of targeted and immunotherapy agents has allowed for successful and less invasive surgery for patients with locally advanced melanoma.
In the NeoCombi trial (Lancet Oncol. 2019;20:961-971), the combination of neoadjuvant therapy with the targeted agents dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) was investigated in patients with stage IIIC melanoma with the BRAF V600 mutation. Of the 35 trial participants, 86% had responded by the time of resection, and nearly half (46%) achieved a complete response. The two-drug combination made it easier for the tumor and surrounding tissue to be surgically excised in 46% of the patients. Toxicities were generally similar to those that have previously been reported among patients who received these therapies for metastatic disease.
The OpACIN-neo trial involved the use of two immunotherapies, ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (Opdivo, Bristol-Myers Squibb), in patients with resectable stage III melanoma. Several dosing schedules were evaluated (Lancet Oncol. 2019;Jul 20:948-960). Among patients who received ipilimumab 1 mg/kg and nivolumab 3 mg/kg every 3 weeks for two cycles, the radiologic objective response rate was 57%, and the pathologic response rate was 77%. In addition, fewer grade 3/4 adverse events were reported during the first 12 weeks as compared with standard dosing (ipilimumab 3 mg/kg plus nivolumab 1 mg/kg every 3 weeks for four cycles). These data suggest that reducing the dose of ipilimumab and nivolumab in this setting could make treatment more tolerable while maintaining efficacy, although long-term outcomes are needed before this approach can be recommended as the standard of care, the report notes.
Elimination of "Surgery First" Approach in Kidney Cancer
Surgery has traditionally been the primary treatment for many solid tumor cancers, including renal cell carcinoma (RCC), but results from two recently published trials suggest that some patients can skip surgery.
Results of the CARMENA trial showed that therapy with sunitinib (Sutent, Pfizer) alone was comparable to cytoreductive nephrectomy followed by sunitinib in 450 patients with metastatic RCC (N Engl J Med. 2018;379:417-427). The median overall survival for patients who received only sunitinib was 18.4 months, compared with 13.9 months for patients who underwent surgery and received sunitinib. Median overall survival with sunitinib was also longer for patients who had been classified as having a poor or intermediate chance of survival (23.4 months vs 19.0 months and 13.3 v 10.2 months, respectively). Adverse events of grade 3 or higher were slightly higher for the sunitinib-only arm (42.7% vs 32%).
In the SURTIME trial, results showed that a surgery-first approach did not improve the progression-free survival rate as compared to giving sunitinib up front prior to cytoreduction (JAMA Oncol. 2019;5:164-170). In a cohort of 99 patients with primary clear cell metastatic RCC, progression-free survival was comparable for the two cohorts (42% vs 43%) at 28 weeks. However, median overall survival favored the patients who received sunitinib up front and for whom surgery was delayed, at 32.4 months vs 15.0 for immediate surgery.
Surgery Made Possible for Pancreatic Cancer
In pancreatic cancer, surgical resection offers the best chance for survival, but many patients are only diagnosed after the disease has advanced to the point that the patient is ineligible for resection. Two preliminary studies suggest that up-front systemic therapy may allow some patients to go on to have surgery, although confirmation is needed from randomized trials, the report notes.
In a single-arm phase 2 study, neoadjuvant FOLFIRINOX plus radiotherapy was evaluated in 48 patients with borderline resectable pancreatic ductal adenocarcinoma (JAMA Oncol. 2018;4:963-969). Patients were restaged following treatment. Those with resolution of vascular involvement received a short course of proton radiotherapy with capecitabine. Standard radiotherapy with fluorouracil or capecitabine was given to those with persistent vascular involvement. Median progression-free survival for the entire cohort was 14.7 months, and overall survival was 37.7 months. Of the 31 patients who underwent surgery, 67% achieved negative margins; progression-free survival was significantly improved in this group (48.6 months). Median overall survival had not been reached, but overall survival at 2 years was 72% for the surgical group vs 56% for all patients.
A second single-arm phase 2 study evaluated patients with locally advanced pancreatic cancer who received FOLFIRINOX and losartan, a renin-angiotensin-aldosterone system mediator (JAMA Oncol. 2019;5:1020-1027). Those with radiographically resectable tumors also received short-course proton radiotherapy and capecitabine; patients with persistent vascular involvement received standard long-course radiotherapy with fluorouracil or capecitabine. The results showed that 61% of the cohort underwent surgery that resulted in negative surgical margins. Median progression-free survival was 17.5 months, and overall survival was 31.4 months for the entire group, compared to 21.3 months and 33 months for those who underwent resection.
J Clin Oncol. Published online February 4, 2020. Full text
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