A Prospective Phase II Trial of Deintensified Chemoradiation Therapy for Low Risk HPV Associated Oropharyngeal Squamous Cell Carcinoma

Transcription

1

2 A Prospective Phase II Trial of Deintensified Chemoradiation Therapy for Low Risk HPV Associated Oropharyngeal Squamous Cell Carcinoma B. S. Chera 1, R. J. Amdur 2, J. E. Tepper 3, B. Qaqish 4, R. Green 5, N. N. Hayes 5, J. Weiss 6, J. Grilley-Olson 5, A. Zanation 5, T. Hackman 7, W. Funkhouser 5, N. C. Sheets 8, M. Weissler 5, and W. M. Mendenhall 9 1 UNC School of Medicine, Chapel Hill, NC, 2 University of Florida Hospitals, Gainesville, FL, 3 University of North Carolina Hospitals, Chapel Hill, NC, United States, 4 University of North Carolina, Chapel Hill, NC, 5 University of North Carolina School of Medicine, Chapel Hill, NC, 6 University of North Carolina, Chapel Hill, Chapel Hill, NC, 7 University of North Carolina at Chapel Hill, Chapel Hill, NC, 8 Rex/UNC, Raliegh, NC, 9 University of Florida, Gainesville, FLa

3 Background Standard Chemoradiotherapy for Oropharyngeal Cancer Radiation: o 70 2 Gy/day, 35 days Chemotherapy: o Concurrent Cisplatin (100 mg/m2 X 3 doses) Surgery: o Only if PET/CT positive 12 weeks post-treatment HPV Many are cured but most live with side effects

4 Eligibility o T0-3, N0 to N2c, M0 Methods o Oropharyngeal or Unknown primary o Squamous cell carcinoma, HPV and/or p16 + o Minimal smoking history De-intensified Chemoradiotherapy o 60 Gy at 2 Gy/day, daily, 6 weeks (IMRT) o Cisplatin 30mg/m2, 6 weekly doses Planned biopsy and limited neck dissection Radiotherapy è 10 Gy reduction Chemotherapy è 40% reduction

5 Results Complete Pathological Response Total (N=43) 37/43 (86%) (all microscopic foci) Primary (2 were T0) Neck (4 were N0) 40/41 (98%) 33/39 (84%) All patients alive with no evidence of cancer recurrence o Median f/u 21 months (4-41 months) o 38 (86%) have at least 1 year of follow-up

6 Results PRO-CTCAE Severity = Very Severe 3 = Severe 2 = Moderate 1 = Mild 0= None 0 Pre-treatment (n=44) 6-8 weeks post chemoradiotherapy (n=42) Timepoint 6 mo post tx start (n=36) 12 mo post tx start (n=33) Appetite Tasting Swallowing Dry mouth

7 Conclusions Complete pathological response rate with 60 Gy of radiation with weekly low dose cisplatin is very high in favorable risk oropharyngeal squamous cell carcinoma Early patient reported outcomes are encouraging NRG Oncology is evaluating UNC regimen in a Phase II randomized study (HN002)

8

9 Accelerated partial breast irradiation (APBI) using sole interstitial multicatheter brachytherapy versus whole breast irradiation with boost after breast conserving surgery for low risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomized phase 3 non-inferiority trial V. Strnad 1, C. Polgar 2, O. Ott 1, G. Hildebrandt 3, D. Kauer-Dorner 4, H. Knauerhase 3, T. Major 2, J. Lyczek 5, J. L. Guinot 6, P. Niehoff 7, C. Gutierrez Miguelez 8, and W. Uter 9 1 University Hospital Erlangen, Erlangen, Germany, 2 National Institute of Oncology, Budapest, Hungary, 3 University Hospital, Rostock, Germany, 4 University Hospital AKH, Wien, Austria, 5 Podkarpacki Regional Cancer Center, Brzozow, Poland, 6 Valencian Institute of Oncology, Valencia, Spain, 7 University Hospital, Kiel, Germany, 8 Catalan Institute of Oncology, Barcelona, Spain, 9 University-Erlangen-Nuremberg, Erlangen, Germany

10 Background April July 2009, ~1200 patients; 6.6 year median follow- up

11 Method Breast conserving surgery, low risk breast cancer 1. Patients aged 40 years and older 2. Small tumors (max 3. cm diameter), no metastases 3. Clear resection margins Stratification Accelerated Partial Breast Irradiation with Multicatheter Brachytherapy only 4.5 days Whole Breast Irradiation 6.5 weeks

12 Primary Endpoint Primary objective: 5-y. local recurrence rate WBI group 0 92% (95% CI: %) n.s. VS. APBI group 1 44% (95% CI: %) (p=0 42) Non-inferiority concerning the 5-year rate of local recurrence has been confirmed.

13 Secondary Endpoint 5-y. disease-free survival 5-y. overall survival 94 4% (WBI) versus 95 03% (APBI) (p=0 79) 95 5% (WBI) versus 97 3% (APBI) (p=0 11)

14 Conclusion Adjuvant APBI using multicatheter brachytherapy after breast conserving surgery for early breast cancer is not inferior to adjuvant WBI with tumour bed boost (50 Gy + 10 Gy). This is the first phase III study proving non-inferiority of APBI in comparison to whole breast irradiation for selected early stage breast cancer patients. Based on our results, APBI using multicatheter brachytherapy o o can be considered as a valid alternative treatment option after breast conserving surgery, and can be offered for all low risk breast cancer patients in clinical routine

15

16 A Prospective Clinical Trial Combining Radiation Therapy with Systemic Immunotherapy in Metastatic Melanoma S. M. Hiniker, S. A. Reddy, H. T. Maecker, S. M. Swetter, L. Shura, and S. J. Knox Stanford University, Stanford, CA

17 Background Ipilimumab in the Treatment of Melanoma Ipilimumab blocks the CTLA-4 co-inhibitory receptor Ipilimumab response rate of 5-16% in trials of metastatic melanoma, with durable responses but rare complete responses New methods of potentiating ipilimumab-induced immune responses are needed 1. Weber J, et al. Clin Cancer Res. 2009;; 2. Hodi FS, et al. N Engl J Med. 2010;; 3. Wolchok JD et al. Lancet Oncol. 2010;; 4. Postow MA, et al. N Engl J Med. 2015

18 Background Radiation May Potentiate Immunotherapy Radiation may enhance tumor immunogenicity o Upregulation of MHC class I o Release of tumor antigens and neoantigens o Release of damage-associated molecular patterns (e.g. HMGB1) o Activation of dendritic cells and enhanced cross-presentation of tumor antigens Case reports and a retrospective study have described abscopal effects of radiation in combination with ipilimumab Prospective study of 22 patients treated with radiation and ipilimumab showed an overall response rate of 18% with no significant added toxicity 1. Postow MA, et al. N Engl J Med 2012;; 2. Hiniker SM, et al. N Engl J Med 2012;; 3. Golden EB, et al. Cancer Immunol Res 2013;; 4. Barker CA, et al Cancer Immunol Res 2013;; 5. Twyman-Saint Victor C, et al. Nature. 2015

19 Method 22 patients (median age 62, range 18-65) with stage IV melanoma enrolled on prospective phase II clinical trial Patients had 1-2 irradiated sites, and at least 1 nonirradiated measurable site to assess for abscopal response Ipilimumab given 3mg/kg every 3 weeks for total of 4 doses Radiation was started within 5 days after the start of ipilimumab o Dose/fractionation at discretion of treating physician Primary objective was safety;; secondary assessments were tumor response and biomarker exploration

20 Results Best Response of Non-Irradiated Lesions Change in tumor size (%) Best Response * 200% 150% 100% 50% 0% -50% -100% Patients * non-irradiated lesions only

21 Results Response Rate and Duration of Response 11/22 patients had clinical benefit from therapy, including complete response (CR), partial response (PR), or stable disease (SD) o 3 (14%) patients have achieved ongoing CR at median of 55 weeks follow-up o 3 (14%) had initial PR for median 40 weeks o 5 (23%) had initial SD for median 39 weeks

22 Results Trial Patient with Complete Response Irradiated Abscopal Pre-Treatment 6 Months Post-Treatment

23 Conclusions Radiation can be safely combined with ipilimumab with no additional toxicity A subset of patients can achieve significant clinical benefit from combination therapy Immune response studies suggest that elevated CD8 activated T cells correlate with response and may have potential for use as biomarker Future studies combining radiation with anti-pd-1 agents may further enhance therapeutic benefit

24 Q & A

25 Questions? Contact ASTRO s Press Office in San Antonio, Oct press@astro.org Slides, photos, and a link to the recording will be available following the briefing in ASTRO s online press room: