Treatment of Trodelvy (sacituzumab govitecan-hziy) led to durable antitumor activity with predominant gastrointestinal toxicities in patients with metastatic or locally recurrent head and neck squamous cell carcinoma (HNSCC) who received between one and three prior lines of therapy, according to findings from a phase 2 trial that were presented at the 2023 ESMO Congress.
Within the phase 2 TROPiCS-03 trial, the median patient age was 62 years. Most patients were men (77%), White (77%), current or former smokers (74%) and human papillomavirus negative (51%). Most patients had metastatic disease (86%) and experienced stable disease or progressive disease (86%) as their best response to their last line of prior therapy.
Patients in the trial received one (33%), two (35%) or more than two (33%) prior lines of therapy in the incurable setting and all had received prior chemotherapy and immunotherapy.
Only 51% of patients received prior targeted therapy. Primary sites of disease included the nasopharynx (2%), oropharynx (44%), larynx (26%), nasal (5%) and oral (19%) cavities.
The median duration of treatment was 2.5 months and the median number of cycles received was four. The most common reason for treatment discontinuation was progressive disease.
With 43 patients and at a median follow-up of 7.8 months, the investigator-assessed objective response rate (ORR; percentage of patients within a study that had a complete or partial response to treatment) was 16%.
The best objective responses included confirmed partial response (16%), stable disease (49%) and progressive disease (21%). The clinical benefit rate (CBR) was 28%, and the median duration of response (DOR; period when tumor responds to treatment without progressing) was 4.2 months. At six months, 43% of patients remained in response. The median progression-free survival (PFS; period during and after treatment when a patient lives with the disease but it does not worsen) was 4.1 months.
“(Trodelvy) demonstrated single-agent antitumor activity in heavily pretreated patients with metastatic or locally advanced recurrent HNSCC,” lead study author Dr. Loren Scott Michel, associate attending physician and head and neck oncologist at Memorial Sloan Kettering Cancer Center in New York, said in a presentation of the data. “These preliminary results warrant further investigation of (Trodelvy) for the treatment of (patients with) HNSCC.”
Patients with advanced HNSCC may derive benefit from PD-(L)1 inhibitors but most will develop disease progression.
Trodelvy is a Trop-2-directed antibody-drug conjugate currently indicated for patients with metastatic triple-negative breast cancer who have received at least one prior line of therapy, patients with hormone receptor–positive, HER2-negative metastatic breast cancer and patients with pretreated metastatic urothelial cancer.
Given the high expression of Trop-2 in HNSCC, investigators sought to evaluate Trodelvy in patients with locally recurrent and metastatic disease.
TROPiCS-03 is an ongoing, open-label, multicohort, phase 2 study evaluating Trodelvy in patients with metastatic or locally advanced recurrent solid tumors.
To be eligible for enrollment, patients had to have histologically confirmed metastatic or locally recurrent HNSCC, disease progression after prior platinum-based chemotherapy and anti-PD-(L)1 therapy, measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1.
Additional efficacy findings revealed that 51% of patients with post-baseline tumor assessment experienced any level of tumor reduction and 16% of patients experienced more than a 30% reduction in tumor size.
All patients were evaluable for safety. Any-grade treatment-emergent side effects related to study treatment occurred in all patients. Overall grade 3 or higher treatment-emergent side effects and those related to study treatment occurred in 58% and 44% of patients, respectively.
Serious treatment-emergent side effects and those related to study treatment occurred in 30% and 12% of patients, respectively. Twenty-one percent of patients experienced treatment-emergent side effects that led to dose reduction.
Three deaths occurred due to treatment-emergent side effects, one of which was related to study treatment.
The most common treatment-emergent side effects that occurred in at least 15% of patients were diarrhea (grade 1/2, 45%; grade ≥3, 2%), nausea (40%; 7%), neutropenia (low white blood cell count) (14%; 33%), fatigue (42%; 2%), alopecia (37%; 0%), vomiting (31%; 2%), anemia (21%; 9%), shortness of breath (19%; 7%), decreased appetite (21%; 2%), leukopenia (low white blood cell count) (10%; 9%) and hyponatremia (low sodium levels in blood) (14%; 2%).
“The safety profile of (Trodelvy) was manageable and consistent with its known safety profile, and treatment-emergent (side) effects leading to treatment discontinuation were low, at 5%,” Michel concluded.
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