Dr Mehra on the Implications of Long-Term Data From the E3311 Trial in HPV+ Oropharynx Cancer

Ranee Mehra, MD, professor, medicine, medical oncology; director, Head and Neck Medical Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland Medical System, discusses the implications of the long-term follow-up data from the phase 2 E3311 trial (NCT01898494) investigating transoral surgery followed by adjuvant therapy in patients with human papillomavirus (HPV)–associated oropharynx cancer, as well as future research directions that these findings may prompt.

At a median follow-up of 52.4 months, the 54-month progression-free survival and overall survival rates in the entire population (n = 359) were 90.6% (90% CI, 87.2%-93.1%) and 95.3% (90% CI, 93.0%-96.9%), respectively. Among patients with a smoking history of 10 or fewer pack years (n = 252), these respective rates were 89.9% (90% CI, 85.9%-92.9%) and 95.5% (90% CI, 92.7%-97.2%). Among patients with a smoking history of more than 10 pack years (n = 104), these respective rates were 91.7% (90% CI, 83.9%-95.9%) and 94.6% (90% CI, 89.1%-97.4%; 

Findings from this trial confirm the importance of determining optimal treatment approaches for all patients with HPV-positive oropharynx cancer, Mehra says. One important finding from this trial was that smoking history was not prognostic among patients who underwent surgery followed by risk-adapted adjuvant therapy, Mehra emphasizes, adding that future research may further clarify this finding in this patient population. Other research avenues to evaluate the effects of surgery and adjuvant therapy in patients with oropharynx cancer may include larger, randomized studies that draw on the expertise of oncology professionals across disciplines, Mehra explains.

The E3311 trial was a multidisciplinary effort that included medical oncologists, surgeons, and radiation oncologists, spotlighting the importance of high-level collaboration when treating patients with head and neck cancer, according to Mehra. Importantly, this was also one of the first trials to use a surgical credentialing system to standardize the quality of surgery used in the study, Mehra concludes.

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Ranee Mehra, MD, discusses long-term follow-up data from the phase 2 E3311 trial in patients with HPV-associated oropharynx cancer.

Dr Mehra on the Implications of the E3311 Trial in HPV+ Oropharynx Cancer

Ranee Mehra, MD, discusses long-term results for primary transoral surgery followed by reduced postoperative radiation in HPV-associated oropharynx cancer.

Ranee Mehra, MD, professor of medicine; director, Head and Neck Medical Oncology; head, Solid Tumor Section; and interim associate director, Clinical Research, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, discusses long-term results from the phase 2 E3311 trial (NCT01898494) exploring primary transoral surgery and postoperative radiation deintensification strategies for patients with human papillomavirus (HPV)–associated oropharynx cancer.

During the study, patients with HPV-associated oropharynx cancer underwent transoral resection with neck dissection, and postoperative treatment was based on risk. Patients with low-risk disease underwent observation (arm A); those with high-risk disease received intensity-modulated radiation therapy (IMRT) at 66 Gy in 33 fractions in combination with cisplatin (arm D). Notably, patients with intermediate-risk disease were randomly assigned to receive IMRT at 50 Gy in 25 fractions (arm B) or 60 Gy in 30 fractions (arm C).

Findings presented at the 2024 ASCO Annual Meeting showed that at a median follow-up of 52.4 months, progression-free survival (PFS) and overall survival (OS) data remained favorable across all treatment groups, Mehra explains. The 54-month PFS rates were 93.2% for arm A, 94.9% for arm B, 90.2% for arm C, and 85.5% for arm D. The respective 54-month OS rates were 97.1%, 97.9%, 95.1%, and 92.5%.

Notably, smoking history did not influence outcomes across treatment cohorts, Mehra says. However, in arm A, 14.8% of patients with N1 disease (n = 27) experienced recurrence, whereas no patients with N0 disease in this arm (n = 11) had disease recurrence. Mehra explains that the recurrence observed in patients with low-risk, N1 disease warrant further exploration.

Mehra adds that in arm D, patients with high-risk oropharynx cancer—defined as either extra nodal-extension or positive surgical margins—experienced favorable outcomes relative to historical controls when treated with radiation and cisplatin. However, despite intensified therapy, patients in this arm had numerically lower 5-year OS and PFS rates compared with other groups, suggesting the need for more aggressive treatment approaches for those with higher-risk disease.

Dr Mehra on Transoral Surgery and Risk-Based Radiation in HPV+ Oropharynx Cancer

Ranee Mehra, MD, chief of Head and Neck Oncology at Fox Chase Cancer Center, discusses challenges in head and neck cancer.

Symptom management is key in head and neck cancer, said Mehra. A small growth in a tumor can result in significant changes in speech or swallowing function.

The patient population of head and neck cancer is unique in that they really can be very symptomatic from advanced locoregional disease, said Mehra.

As new combinations of therapies are developed, it is important to keep in mind that there is a need for palliative care for these patients through treatment, she added.

Dr. Ranee Mehra on the Importance of Symptom Management in Head and Neck Cancer

Ranee Mehra, MD, Medical Oncology, head and neck care team, lung cancer care team, Fox Chase Cancer Center, discusses the use of DNA repair enzymes, such as ERCC1, as predictive markers for resistance and survival in head and neck cancer patients.

Mehra explains that in a retrospective tumor sample analysis of patient that had received induction regimens follow by radiation or concurrent chemo radiation there was a clear trend towards improved response and survival outcomes for the patients with a lower expression of DNA repair enzymes.

This retrospective analysis will help establish further hypotheses. The role of DNA repair enzymes needs further investigation but does suggest a possible connection between low levels of the marker and resistance to platinum based or radiation therapy.

Dr. Ranee Mehra from Fox Chase Cancer Center Discusses DNA Repair Enzymes

Ranee Mehra, MD

Articles

Dr Mehra on the Implications of the E3311 Trial in HPV+ Oropharynx Cancer

Dr Mehra on Transoral Surgery and Risk-Based Radiation in HPV+ Oropharynx Cancer

Dr. Ranee Mehra on the Importance of Symptom Management in Head and Neck Cancer

Dr. Mehra Discusses DNA Repair Enzymes