Dr Sun on Managing TEAEs of Tisotumab Vedotin in Recurrent/Metastatic HSNCC

Lova L. Sun, MD, MSCE, assistant professor, medicine (hematology-oncology), Department of Medicine, the Hospital of the University of Pennsylvania, discusses safety findings observed from part C of the phase 2 innovaTV 207 trial (NCT03485209), which evaluated the efficacy and safety of tisotumab vedotin-tftv (Tivdak) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who received prior treatment with platinum-based chemotherapy and/or an immune checkpoint inhibitor. She also explains the importance of managing adverse effects (AEs) in patients being treated with antibody-drug conjugates (ADCs).

Sun emphasizes that managing toxicity is a pivotal aspect of treating patients with an ADC, since these agents have both a cytotoxic payload and a targeting mechanism.

Updated data from innovaTV 207 presented at the 

 showed that the safety profile of tisotumab vedotin remained consistent with findings from previous studies evaluating the agent as monotherapy. Any-grade treatment-emergent AEs (TEAEs) occurred in 95.0% of patients with HNSCC treated with tisotumab vedotin (n = 40). The rate of grade 3 or higher TEAEs was 67.5%. Serious TEAEs occurred in 47.5% of patients, and TEAEs led to death in 2.5% of patients. Twenty percent of patients discontinued treatment due to TEAEs. AEs of special interest leading to treatment discontinuation included ocular events (7.5%), peripheral neuropathy (5.0%), and bleeding events (2.5%).

The most common any-grade TEAEs included peripheral sensory neuropathy (40.0%), constipation (32.5%), conjunctivitis (30.0%), fatigue (30.0%), and decreased appetite (30.0%).

Notably, any-grade ocular TEAEs, including conjunctivitis, were reported in 52.5% of patients. Other any-grade ocular TEAEs consisted of dry eye (17.5%), eye discharge (10.0%), increased lacrimation (10.0%), and ocular hyperemia (10.0%).

Sun notes that collaborating with other clinicians, such as ophthalmologists, can help the mitigation and management of these TEAEs through preventive measures, such as steroid eyedrops. Mitigating and managing TEAEs associated with tisotumab vedotin can help patients remain on treatment and continue to derive benefit, Sun concludes.

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Lova Sun, MD, MSCE, discussions safety implications observed from part C of the phase 2 innovaTV 207 trial. 

Dr Sun on Tisotumab Vedotin in Recurrent or Metastatic HNSCC

Lova L. Sun, MD, MSCE, assistant professor of medicine (hematology-oncology), Department of Medicine, the Hospital of the University of Pennsylvania, discusses data from part C of the phase 2 innovaTV 207 trial (NCT03485209), which evaluated the efficacy and safety of tisotumab vedotin-tftv (Tivdak) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who received prior treatment with platinum-based chemotherapy and/or an immune checkpoint inhibitor.

Tisotumab vedotin was administered intravenously at 1.7 mg/kg once every two weeks in the HNSCC cohort. Findings presented at the 2024 ASCO Annual Meeting showed that among all patients treated in cohort C (n = 40), the confirmed objective response rate (ORR) was 32.5% (95% CI, 18.6%-49.1%), with a median duration of response (DOR) of 5.6 months (95% CI, 3.0–not reached [NR]). One patient (2.5%) experienced a complete response (CR), and the partial response (PR) rate was 30.0%. The rates of stable disease (SD) and progressive disease (PD) were 32.5% and 25.0%, respectively, and the disease control rate (DCR) was 42.5% (95% CI, 27.0%-59.1%). Notably, among these 25 patients being treated in the second- or third-line settings, 40% experienced a reduction in target lesion diameters of at least 30%.

Among a subgroup of 25 patients who were being treated in the second or third line (n = 25), the confirmed ORR was 40.0% (95% CI, 21.1%-61.3%) with a median DOR of 5.6 months (95% CI, 3.0-NR). The respective CR, PR, SD, and PD rates in this subgroup were 0%, 40.0%, 24.0%, and 28.0%. The DCR was 52.0% (95% CI, 31.3%-72.2%).

Responses were observed in patients irrespective of prior taxane exposure, Sun says, adding that deeper responses were more common in taxane-naive patients, which was expected given the MMAE payload mechanism of tisotumab vedotin.

The innovaTV 207 trial is ongoing, and it continues to enroll patients with recurrent or metastatic HNSCC being treated in the first-line setting (part F) and the second- or third-line settings (part E).

Lova L. Sun, MD, MSCE discusses tisotumab vedotin (in patients with recurrent or metastatic (r/m) head and neck squamous cell carcinoma.

Lova L. Sun, MD, MSCE, assistant professor of medicine, the Hospital of the University of Pennsylvania, Penn Medicine, discusses the association between duration of immunotherapy and overall survival (OS) in patients with advanced non–small-cell lung cancer (NSCLC).

A real-world study utilized data from the electronic health record–derived Flatiron Health database to further assess practice patterns surrounding the discontinuation of immune checkpoint inhibitor therapy at 2 years, and to evaluate if there was an OS benefit associated with indefinite vs fixed duration immunotherapy.

Data presented in a posted at the 2023 ASCO Annual Meeting showed that there was no statistically significant difference in OS between patients who stopped immunotherapy at 2 years vs those who continued treatment beyond 2 years, Sun begins. In patients treated with fixed-duration therapy (n = 113), the 3- and 4-year OS probabilities were 0.89 and 0.79, respectively. In the indefinite therapy group (n = 593), the 3- and 4-year OS probabilities were 0.91 and 0.81, respectively.

Another major finding of this study was that only 1 in 5 patients who were progression free discontinued treatment at 2 years. This suggests that the vast majority of patients in the United States are continuing treatment beyond 2 years in the absence of progression, Sun explains, noting that indefinite treatment could have implications on financial and medical toxicities.

Sun explains that this research was not designed to provide a definitive answer on whether patients should stop immunotherapy at 2 years. Rather, the real-world study aimed to question if stopping immunotherapy at 2 years may be a safe and a reasonable approach in the absence of randomized clinical trial data, Sun continues. Proposed randomized clinical trials could evaluate fixed-duration vs indefinite immunotherapy in a prospective setting, she expands. However, these trials would likely to take a significant amount of time to accrue patients and produce results, Sun concludes.

Lova L. Sun, MD, MSCE, discusses the association between duration of immunotherapy and overall survival in patients with advanced non–small-cell lung cancer.


Lova L. Sun, MD, MSCE

Articles

Dr Sun on Managing TEAEs of Tisotumab Vedotin in Recurrent/Metastatic HSNCC

Dr Sun on Tisotumab Vedotin in Recurrent or Metastatic HNSCC

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