Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Neoadjvuant cemiplimab has achieved pathological complete response (pCR) in around half of patients with resectable cutaneous squamous cell carcinoma (CSS) participating in a phase II trial.
The findings of the multicentre, nonrandomised study of the PD-1 inhibitor were presented at the ESMO Congress 2022 in Paris, France, and simultaneously published in The New England Journal of Medicine.
The 79 adults were aged a median 73 years and 85% were men. All patients were eligible for primary surgery for stage II (6.3%), III (48.1%) or IV disease without distant metastases (45.6%), most commonly in the head and neck (91%), and had not been treated with radiotherapy, report Neil Gross, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.
After a 12-week course of cemiplimab 350 mg given every 3 weeks the patients underwent surgery with curative intent.
At this time, independent review of surgical specimens indicated pCR in 51% of patients. A further 13% of patients achieved a pathological major response, defined as viable tumour cells in up to 10% of the surgical specimen, whereas 25% did not meet either response criteria and 11% did not undergo surgery on day 75–100 of the study.
The objective response rate (ORR), as assessed by the study investigators, was 68%, with complete and partial responses in 6% and 62%, respectively, and stable disease in 20%, giving a disease control rate of 89%. Ten percent of patients had progressive disease and one patient did not undergo imaging.
Neil Gross and co-authors comment that “the discordance between the percentage of patients with a complete response on imaging (6%) and the percentage of patients with a pathological complete response (51%) may show the inherent technical limitation of contemporary cross-sectional imaging, underscoring the importance of tissue confirmation and highlighting the need for alternative methods of response assessment.”
Of the 11% of patients who did not undergo surgery, five had a partial response on imaging, of whom three declined surgery, one was lost to follow-up and one died. Of the remaining patients who did not undergo surgery, two had progressive, inoperable disease, one patient had progression and did not attend follow-up, and one patient died.
The investigators report that the median duration of cemiplimab exposure was 12 weeks and 78.5% of patients received all four doses, with disease progression based on imaging (n=8) or clinical evaluation (n=3) the most common reasons for discontinuation.
Treatment-related adverse events (TRAEs) of any grade occurred in 72% of patients, most commonly any-grade fatigue (28%), maculopapular rash (14%) and diarrhoea (11%). Immune-related AEs occurred in 15% including grade 3 events in 4%.
Of the four fatal events, only exacerbation of congestive heart failure in a 93-year-old woman with other comorbidities was considered “possibly related to treatment”, Neil Gross and co-authors comment.
Biomarker analysis of 56 patients with baseline PD-L1 tumour proportion scores showed that while pathological responses occurred regardless of PD-L1 expression, the pCR was higher among patients with a score of at least 1% than those with a lower score (54 vs 20%), as was the ORR (76 vs 47%).
Fifty patients were assessed for tumour mutational burden (TMB); patients with a TMB above the median 58.5 mutations/megabase were more likely than those below this threshold to achieve a pCR (56 vs 20%) or an ORR (80 vs 56%).
However, the researchers note that there was a “wide range” of TMB values in patients with and without pCR and therefore “no correlations can be made between efficacy and [TMB]”.
They emphasize that neither PD-L1 tumour expression nor TMB are “adequate biomarkers to guide decisions regarding neoadjuvant therapy with cemiplimab.”
Neil Gross et al conclude that, taken together, their findings “suggest that neoadjuvant cemiplimab has high therapeutic activity in patients with resectable cutaneous squamous-cell carcinoma.”
They continue: “The potential for function-preserving surgery, together with the high frequency of a pathological complete response, supports the use of neoadjuvant therapy with cemiplimab in this patient population.”
References
7890 - Gross N, Miller DM, Khushanlani N, et al. Neoadjuvant cemiplimab in patients with stage II-IV (M0) cutaneous squamous cell carcinoma: Primary analysis of a phase II study. Ann Oncol 2022; 33 (suppl_7): S356–S409. Doi: 10.1016/annonc/annonc1059
Gross ND, Miller DM, Khushalani NI, et al. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N Engl J Med; Advance online publication 12 September 2022. DOI:10.1056/NEJMoa2209813
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