Therapeutic Advancements Have Facilitated Surgery Optimization, ASCO Officials Report

The American Society of Clinical Oncology (ASCO) has named “refinement of the surgical treatment of cancer” as the 2020 Advance of the Year within the field of oncology clinic research. This announcement was made in “Clinical Cancer Advances 2020: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology,” which was published in the Journal of Clinical Oncology.

“Therapeutic enhancements that contributed to improvements in surgical practice and timing, wrote ASCO’s President, Howard A. “Skip” Burris III, MD, FACP, FASCO, have specifically contributed to “less invasive approaches for advanced melanoma, reduced the need for surgery in renal cell carcinoma, and increased the number of patients with pancreatic cancer who can undergo surgery.”

Since 2006, there have been more than 150 new therapies or indications approved by the US Food and Drug Administration (FDA) in the cancer space, which likely contributed to the dramatic decline in cancer death rates in the last 30 years. In fact, according to ASCO’s calculations, 2 out of 3 people with cancer now live at least 5 years after their initial cancer diagnosis.

In the case of melanoma, researchers found that administering immunotherapy in the neoadjuvant setting allowed for less invasive surgery. Neoadjuvant treatment with dabrafenib and trametinib in patients who had stage IIIC disease characterized by a BRAF V600 mutation “made it easier to surgically remove the tumor and surrounding tissue” in nearly half of the 35 patients studied, and almost half of the study participants had a complete response to the combination (ClinicalTrials.gov Identifier: NCT01972347). And, reducing the neoadjuvant dosing of ipilimumab plus nivolumab in stage III melanoma in OpACIN-neo allowed high-risk patients to experience benefit from a combination immunotherapy approach, while incurring fewer adverse effects compared with those seen with normal dosing protocols (ClinicalTrials.gov Identifier: NCT02977052).

The availability of targeted therapies in metastatic renal cell carcinoma (mRCC) provided options outside of immediate surgery, and the use of these medications in the upfront setting expanded the cohort of patients with pancreatic cancer who would be eligible to consider surgery as a treatment option.

For both of the developments flagged by ASCO as being practice changing in kidney cancer, sunitinib was the main drug under investigation — and it was found to be no worse than surgery (ie, comparable to cytoreductive nephrectomy followed by sunitinib) in mRCC in the CARMENA trial (ClinicalTrials.gov Identifier: NCT00930033). In the SURTIME trial of 99 patients, treatment for mRCC with sunitinib prior to cytoreductive nephrectomy (CN) led to progression-free survival rates (PFRs) that were similar to those seen in patients who underwent immediate CN followed by postsurgical sunitinib (ClinicalTrials.gov Identifier: NCT01099423). The benefit of sunitinib in the adjuvant setting in RCC, however, was less clear: data on sunitinib as an adjunctive therapy were mixed, and in patients with a high risk of disease recurrence, treatment with the drug in this setting was linked to a worse health-related quality of life (HRQoL) compared with placebo.

Survival gains in RCC were also seen in the KEYNOTE-426 trial (ClinicalTrials.gov Identifier: NCT02853331), which studied pembrolizumab plus axitinib, and the JAVELIN Renal 101 trial (ClinicalTrials.gov Identifier: NCT02684006), which studied avelumab plus axitinib.

For pancreatic malignancies that have metastasized, progress has allowed oncologists to make better treatment decisions for patients who have tumors that were previously thought to be unresectable. The ASCO panel cited examples from 2 single-arm trials based on FOLFIRINOX (ClinicalTrials.gov Identifier: NCT01591733 and ClinicalTrials.gov Identifier: NCT01821729). One trial was in borderline-resectable pancreatic ductal adenocarcinoma and the other combined losartan with neoadjuvant FOLFIRINOX in patients with locally advanced pancreatic cancer.

The authors went on to commend the identification and collection of molecular biomarkers as another key area of recent progress. They cited the POLO trial in metastatic pancreatic cancer (ClinicalTrials.gov Identifier: NCT02184195) as a success in patients with germline BRCA mutations, as there was a statistically significantly improvement in PFS for patients in the olaparib arm. The existence of a methylated MGMT gene promoter in glioblastoma appeared to make tumors more sensitive to treatment with temozolomide (ClinicalTrials.gov Identifier: NCT01149109), and patients with mutations in BRAF V600 in metastatic colorectal cancer did worse with study treatment compared with those patients who had wild-type BRAF, according to investigators from the BEACON trial (ClinicalTrials.gov Identifier: NCT02928224).

Local consolidative therapy in non-small cell lung cancer (NSCLC) was found to extend survival in select patients (ClinicalTrials.gov Identifier: NCT01725165), open surgery in cervical cancer was found to be more effective than minimally invasive approaches for some (ClinicalTrials.gov Identifier: NCT00614211), and stereotactic radiation for metastases was found to prolong overall survival (ClinicalTrials.giv Identifier: NCT01446744).

The report also summarized a variety of other important strides made in cancer treatment outside of surgery within the last year.

The authors highlighted that in HPV-positive squamous cell carcinoma, cisplatin plus radiotherapy became the standard of care. They also noted the use of pembrolizumab in head and neck squamous cell carcinoma across 2 trials — KEYNOTE-040 (ClinicalTrials.gov Identifier: NCT02252042) and KEYNOTE-048 (ClinicalTrials.gov Identifier: NCT02358031)

A study in for extensive-stage small cell lung cancer (SCLC), IMpower 133 (ClinicalTrials.gov Identifier: NCT02763579) led to the FDA approval of atezolizumab in combination with frontline chemotherapy in March 2019. Meanwhile, the addition of checkpoint inhibitors in NSCLC prolonged overall survival in select patient cohorts, such as observed in the PACIFIC trial (ClinicalTrials.gov Identifier: NCT02125461) and in the KEYNOTE-407 trial (ClinicalTrials.gov Identifier: NCT02775435).

Results of the KATHERINE trial (ClinicalTrials.gov Identifier: NCT01772472), IMPassion130 trial (ClinicalTrials.gov Identifier: NCT02425891), and the MONALEESA-7 trial (ClinicalTrials.gov Identifier: NCT02278120) across various cohorts of patients with breast cancer were revealed to be pivotal in regard to recurrence, progression, and survival, respectively.

In prostate cancer, the addition of enzalutamide in the ENZAMET trial boosted survival for some men (ClinicalTrials.gov Identifier: NCT02446405). Lomustine added to temozolomide appeared to help survival in select cases of glioblastoma (ClinicalTrials.gov Identifier: NCT01149109).

A variety of therapies across drug classes were trialed for their efficacy in hepatocellular carcinoma (HCC): KEYNOTE-224 (ClinicalTrials.gov Identifier: NCT02702414), CELESTIAL (ClinicalTrials.gov Identifier: NCT01908426), and REACH-2 (ClinicalTrials.gov Identifier: NCT02435433).

Children and young patients with cancer were of specific interest across a few important trials, the authors noted. These included a trial in T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma trial (ClinicalTrials.gov Identifier: NCT00408005), a liver cancer trial (ClinicalTrials.gov Identifier: NCT00980460) and a glioma trial (ClinicalTrials.gov Identifier: NCT01089101).

Important and/or pivotal trials highlighted in ASCO’s annual report also included the AUGMENT trial in non-Hodgkin lymphoma (ClinicalTrials.gov Identifier: NCT01938001) and a trial in follicular and marginal-zone lymphoma (ClinicalTrials.gov Identifier: NCT01938001), as well as SOLO-1 in advanced ovarian cancer (ClinicalTrials.gov Identifier: NCT01844986).

In locally advanced metastatic bladder cancer, trials testing novel targeted therapies included a study looking at erdafitinib (ClinicalTrials.gov Identifier: NCT02365597) and another trial that examined the use of antibody-drug conjugate enfortumab vedotin following the failure of chemotherapeutic and checkpoint inhibition agents (ClinicalTrials.gov Identifier: NCT03219333).

The were also some additional, more subtle treatment trends noted in the report that all centered around a common theme: harm reduction in oncology. The authors from ASCO noted that studies examining combination regimens in cancer have demonstrated that improved survival does not always have to be coupled with toxicity increases — and that the improved adoption of vaccines for human papillomavirus (HPV) has helped reduce the risk of cervical cancer in the real world. It was also noted that investigators can likely put to rest a theory that vitamin D prevents cancer as researched have determined that vitamin D supplementation has no influence on cancer incidence or mortality.

The authors concluded their report with the suggestion that further refinements in the practice of treating cancer should include better ways to predict patient response and resistance to therapies prior to administration. They also noted the needed improvement in efforts to deliver cancer care to populations with the highest burden of unmet need, including patients who are obese, are older and potentially more frail, those who have rare cancers with few treatment options, or pediatric patients. There is also a need for better screening of premalignant lesions, the identification of better predictive and prognostic biomarkers, and the increased use of systemic therapies as a method of limiting the scope of surgical interventions that would be required.

Reference
Markham MJ, Wachter K, Agarwal N, et al. Clinical cancer advances 2020: Annual report on progress against cancer from the American Society of Clinical Oncology [published online February 4, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.03141

This article originally appeared on Cancer Therapy Advisor