Axel Hauschild, MD, PhD, discusses the role of adjuvant and neoadjuvant therapy in melanoma, highlighting the utility of perioperative approaches.

Dr Hauschild on the Role of Adjuvant/Neoadjuvant Therapy in Melanoma Management

Axel Hauschild, MD, PhD, head, Skin Cancer Trial Center, University Hospital Schleswig-Holstein, discusses the role of adjuvant and neoadjuvant therapy in melanoma management, as well as highlights the benefits and limitations of perioperative treatment approaches in this disease setting.

The utility of adjuvant and neoadjuvant treatment in patients with melanoma has evolved over the past 5 to 10 years, Hauschild begins. Adjuvant treatments, including PD-1 antibodies as well as BRAF and MEK inhibitors, have yielded notable improvements in relapse-free survival for patients, he states. However, recent data with neoadjuvant ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with resectable stage III disease and lymph node metastases are equally compelling, Hauschild reports. Neoadjuvant treatment can result in complete responses (CRs) confirmed by histopathology, potentially eliminating the need for adjuvant therapy, he explains. Accordingly, these patients are spared its associated toxicities, although neoadjuvant therapy also carries its own adverse effects, Hauschild adds. 

The use of a neoadjuvant, adjuvant, or perioperative approaches is often dependent on physician preference, cost considerations, and patient factors, Hauschild continues. He considers perioperative treatment to be a beneficial approach, as it involves a similar number of cycles and toxicity profile as adjuvant therapy without additional costs. For example, perioperative pembrolizumab (Keytruda) is administered for 1 year, with 3 cycles given before surgery and the remaining cycles administered post-surgery. This schema is appealing for its practicality and potential effectiveness, Hauschild states. Nevertheless, a neoadjuvant only regimen should be considered for patients achieving pathologically confirmed CRs, he reiterates.

Both neoadjuvant and adjuvant treatment modalities are likely to play integral roles in future melanoma management, Hauschild emphasizes. Randomized phase 3 clinical trials leading to the approval of more neoadjuvant or adjuvant approaches are highly anticipated in Germany, as in many other countries. Therefore, the continued exploration and validation of these therapies through rigorous clinical trials are crucial for their integration into standard practice and essential for proper reimbursement, Hauschild concludes.

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Dr Hauschild on Ongoing Research With Adjuvant Immunotherapy in CSCC

Axel Hauschild, MD, PhD, head, Skin Cancer Trial Center, University Hospital Schleswig-Holstein, discusses ongoing research that may further define the use of adjuvant immunotherapy for patients with cutaneous squamous cell carcinoma (CSCC), as well as current indications for immunotherapy in patients with basal cell carcinoma.

Several global treatment guidelines do not currently include recommendations for adjuvant therapy in CSCC, Hauschild says. Since chemotherapy is not a feasible treatment option for these patients, 2 clinical trials are exploring the use of adjuvant immunotherapy in this population, Hauschild explains. The phase 3 C-POST trial (NCT03969004) is evaluating adjuvant cemiplimab-rwlc (Libtayo) vs placebo in patients with high-risk CSCC who have received surgery and radiation therapy. The phase 3 KEYNOTE-630 trial (NCT03833167) is investigating adjuvant pembrolizumab (Keytruda) compared with placebo in patients with high-risk, locally advanced disease. In the context of these trials, “high risk” refers to patients with CSCC at high risk for relapse after surgery, Hauschild notes. Although findings from these trials have yet to be reported, by the end of 2024, these data will be mature enough to potentially impact guideline changes for the adjuvant treatment of patients with CSCC, Hauschild emphasizes.

In the United States and Europe, cemiplimab is indicated for the second-line treatment of patients with locally advanced or metastatic basal cell carcinoma who have exhibited best responses of stable disease or progressive disease on a hedgehog inhibitor (HHIs), including sonidegib (Odomzo) or vismodegib (Erivedge). Patients may also receive second-line cemiplimab if they are intolerant to or ineligible for HHIs, which is a common occurrence, according to Hauschild.

Notably, the overall response rate (ORR) with second-line cemiplimab in patients with basal cell carcinoma is approximately 32%, which is much lower than the approximate ORR of 50% observed with this agent in the frontline treatment of patients with other cutaneous malignancies, Hauschild says. This disparity between ORRs is expected, as pretreated patients tend to respond less favorably to second-line therapy vs patients who receive the same agent in the first line, Hauschild explains. Further research is needed to determine the efficacy of frontline cemiplimab in patients with basal cell carcinoma, Hauschild concludes.

Axel Hauschild, MD, PhD, discusses research with adjuvant immunotherapy in CSCC and immunotherapy indications in basal cell carcinoma.

Axel Hauschild, MD, of University Hospital, Schleswig-Holstein, Germany, discusses the phase III, randomized, BREAK-3 trial that compared the BRAF inhibitor dabrafenib to dacarbazine for patients with 

Hauschild notes that the BREAK-3 trial was similar in design to the BRIM3 trial that investigated the BRAF inhibitor vemurafenib in advanced melanoma. The two trials both enrolled only patients with confirmed 

-mutations; however, they used different tests to detect the 

 mutation. The BRIM3 trial used the now FDA approved cobas 4800 BRAF v600 test and the BREAK-3 trial confirmed the mutation using an allele-specific PCR assay, developed by a GSK collaborator. The 

 mutation occurs in approximately 90% of all 

 mutations — an abnormality that occurs in 40-50% of all melanoma patients.

In the trial, 250 patients with previously untreated, unresectable, stage III or IV 

-mutated melanoma were randomized 3:1 to receive either dabrafenib or dacarbazine. The median progression-free survival for the dabrafenib arm was 5.1 months compared to 2.7 months in the dacarbazine arm.

Dr. Axel Hauschild, from University Hospital, Schleswig-Holstein, Germany, Discusses the BREAK-3 Trial That Investigated the BRAF Inhibitor Dabrafenib.


Axel Hauschild, MD

Articles

Dr Hauschild on the Role of Adjuvant/Neoadjuvant Therapy in Melanoma Management

Dr Hauschild on Ongoing Research With Adjuvant Immunotherapy in CSCC

Dr. Hauschild Discusses the Dabrafenib BREAK-3 Trial