Head and Neck Cancers Update 2019: Treatment Strategies and Outcomes

Head and Neck Cancers Update 2019 Prakash Neupane MD

Head and Neck 2019 De-escalation Escalation Metastatic disease Salivary gland

De-ESCALaTE HPV- Mehanna et al AJCC – staging, 7th Edition manual: T3N0–T4N0, and T1N1–T4N3) that was classified as low risk as per the Ang classification: • Positive on p16 IHC • A non-smoker or have a lifetime self-reported smoking history of less than 10 pack-years. T3NO or T1 N1 were included

De-ESCALaTE HPV- Mehanna et al • Treatment- Standard daily radiation • Cisplatin 100 mg?m2 days 1,22 and 43 or Cetuximab 400 mg/m2 loading dose followed by 7 weekly treatment of 250mg/m2 • Assessment at 12 weeks from end of RT. • Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group)

De-ESCALaTE HPV- Mehanna et al

De-ESCALaTE HPV- Mehanna et al Conclusion- • Cetuximab was not less toxic overall when compared to cisplatin • Statistically and clinically significant detriment in tumor control and survival with cetuximab use.

RTOG 1016 • Eligibility criteria included histologically confirmed HPV-positive oropharyngeal carcinoma • American Joint Committee on Cancer 7th edition clinical categories T1–T2, N2a–N3 M0 or T3–T4, N0–N3 M0; (T1-T2 had to be N3) T1N1-2 excluded but T3N0 was included. • Performance status 0-1

RTOG 1016 Treatment- Cisplatin 100mg/m2 on days 1,22 (No day 43). Total 200 mg/m2 in 2 cycles. Cetuximab 400 loading dose followed by 250 mg/m2 weekly concurrently for 7 more doses. Radiation- 2Gy 6 per week for 6 weeks total 70Gy (not 5 days per week)

RTOG 1016

RTOG 1016 Cetuximab and radiation therapy was inferior on overall survival and progression free survival when compared to cisplatin and radiation therapy. Cisplatin and radiation therapy remains the standard of care for this population.

What did we learn? Two large randomized trials in two different continent came to same conclusion- Cisplatin and concurrent radiation therapy remains the standard of care for HPV positive, non smoker patients who are eligible for cisplatin chemotherapy. .

Escalation • Cisplatin and Gemcitabine induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma primary analysis of phase III RCT. • Induction chemotherapy followed by concurrent chemoradiotherapy vs concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma – long term result of phase III multicenter randomized controlled clinical trial Presented By Jun Ma at 2019 ASCO Annual Meeting Presented By Ming-Yuan Chen at 2019 ASCO Annual Meeting

 The most often cited trial in the US : Al- Sarraf et al. INT-0099 Presented By A. Colevas at 2019 ASCO Annual Meeting

Gemcitabine plus Cisplatin (GC) versus Cisplatin plus 5- Fluorouracil (PF) Zhang et al. SYSU. Lancet 2016 Presented By A. Colevas at 2019 ASCO Annual Meeting

Slide 1 Presented By Jun Ma at 2019 ASCO Annual Meeting

CCRT compliance: mean relative dose intensity Presented By Jun Ma at 2019 ASCO Annual Meeting

Primary endpoint: Recurrence-free survival Presented By Jun Ma at 2019 ASCO Annual Meeting

Secondary endpoint: Overall survival Presented By Jun Ma at 2019 ASCO Annual Meeting

Presented By Jun Ma at 2019 ASCO Annual Meeting

Take home message Presented By Jun Ma at 2019 ASCO Annual Meeting

Escalation - 2

Slide 3 Presented By Ming-Yuan Chen at 2019 ASCO Annual Meeting

Recurrent and Metastatic disease “incurable”

Protocol-Specified Final Results of the KEYNOTE-048 Trial of Pembrolizumab as First-Line Therapy for Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) Presented By Danny Rischin at 2019 ASCO Annual Meeting

KEYNOTE-048 Study Design (NCT02358031) Presented By Danny Rischin at 2019 ASCO Annual Meeting

Study End Points: Pembrolizumab vs EXTREME and Pembrolizumab + Chemotherapy vs EXTREME Presented By Danny Rischin at 2019 ASCO Annual Meeting

OS, P+C vs E, CPS ≥20 Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

OS, P+C vs E, CPS ≥1 Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

PFS, P+C vs E, CPS ≥20 and ≥1 Presented By Danny Rischin at 2019 ASCO Annual Meeting

OS, P+C vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

OS, P vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

PFS, P vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

Response Summary, P vs E, Total Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

OS, P vs E, CPS ≥20 Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

OS, P vs E, CPS ≥1 Population Presented By Danny Rischin at 2019 ASCO Annual Meeting

Summary of Overall Survival Presented By Danny Rischin at 2019 ASCO Annual Meeting

FDA approval – June 10th 2019 Pembrolizumab was approved for use in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose tumors express PD‑L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA‑approved test. The FDA also expanded the intended use for the PD-L1 IHC 22C3 pharmDx kit to include use as a companion diagnostic device for selecting patients with HNSCC for treatment with pembrolizumab as a single agent.

Salivary Duct Carcinoma

Slide 4 Presented By Jochen Lorch at 2019 ASCO Annual Meeting

Salivary Gland Cancer: Scope of the problem Presented By Jochen Lorch at 2019 ASCO Annual Meeting

Alliance A091404 Presented By Jochen Lorch at 2019 ASCO Annual Meeting

Slide 10 Presented By Jochen Lorch at 2019 ASCO Annual Meeting

Ado-trastuzumab emtansine in patients with HER2 amplified salivary gland cancers: Results from a phase 2 basket trial Presented By Bob Li at 2019 ASCO Annual Meeting

Slide 3 Presented By Bob Li at 2019 ASCO Annual Meeting

Head and Neck Cancers Update 2019: Treatment Strategies and Outcomes