Kidney Cancer - Online Expert Cancer Consultation - Navya Care

1. Dear , Thank you for reaching out to Tata Memorial Centre (TMC) and nationally acclaimed experts of the National Cancer Grid (NCG). Navya is pleased to offer this online expert cancer consultation service for assessing your treatment options. We converted your case reports into a structured summary to be reviewed a radiation oncologist in the Uro Oncology Disease Management Group at Tata Memorial Centre, an internationally renowned expert radiation oncologist, faculty at UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, and an expert medical oncologist from the National Cancer Grid, a consortium of 206 cancer centers with the mandate to standardize cancer care nationally. We asked the following question(s) on your behalf: 1.Given the intermediate-risk group (as mentioned in the structured summary), what is recommended at this time: immunotherapy or an alternate treatment? 2.Is radiation therapy recommended at this time? 3.Are additional diagnostic tests recommended at this time? The TMC NCG Navya opinion is summarized as follows: 1.Immunotherapy with either one of the options is recommended at this time: a.Immunotherapy with Pembrolizumab and targeted therapy with Axitinib. OR b.Immunotherapy with Ipilimumab and Nivolumab. 2.Given the intermediate risk, debulking nephrectomy (i.e. surgical removal of kidney) is not indicated/recommended at this time. 3.Additionally, diagnostic test with MRI scan of lumbar spine is recommended at this time. 4.Given symptomatic (i.e there are significant symptoms due to the presence of cancer cells/lesion(s)/ tumor(s)) for bone pain, radiation therapy to the painful bony sites to ease/relieve symptoms is recommended. 5.Further, continuing the ongoing bisphosphonate therapy with Denosumab or with Zoledronic acid is recommended. We hope that the expert opinion is helpful in determining the course of your treatment. Please discuss this opinion with your treating oncologist(s). This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 1 authority over the care of any individuals.

2. Navya Evidence and Experience Engine is used to assess treatment options derived from clinical trials that pertain to your specific medical history and tumor characteristics as well as analysis of tumor board decisions of patients similar to you treated at internationally renowned tertiary care expert centers. Navya, who provides online cancer consultation, is pleased to provide the following information on treatment recommendation(s) per the Navya Evidence Engine, which includes the globally accepted guidelines for the treatment of cancers by National Comprehensive Cancer Network (NCCN); and the Navya Experience Engine based on the collective experience of experts at Tata Memorial Center and the National Cancer Grid. 1.Immunotherapy with either of the options are recommended at this time: a.Immunotherapy with Pembrolizumab IV 200 mg once every 3 weeks (Rini 2019) or 400 mg once every 6 weeks along with targeted therapy with Axitinib 5 mg twice daily and until disease progression or dose limiting toxicity. OR b.Immunotherapy with Nivolumab IV 3 mg/kg once every 3 weeks along with Immunotherapy with Ipilimumab IV 1mg/kg once every 3 weeks for up to 4 combination doses, followed by monotherapy with Nivolumab IV 240 mg once every 2 weeks (Motzer 2019) or 480 mg once every 4 weeks until disease progression or dose limiting toxicity. 2.If immunotherapy is not accessible/affordable, targeted therapy with Tyrosine Kinase Inhibitors with either of the following regimens may be considered: a.Sorafenib 400 mg/m2 twice daily until disease progression or dose limiting toxicity . OR b.Sunitinib 50 mg/m2 once daily for four weeks, every six weeks until disease progression or dose limiting toxicity. OR c.Pazopanib 800 mg daily until disease progression or dose limiting toxicity. 3.After completing recommended immunotherapy and/or targeted therapy, assessment of response (i.e. whether the tumor(s)/lesion(s) in the body have decreased/not increased/increased) with CT scans with oral and iv contrast of the chest/abdomen/pelvis or PET CT scan of the whole body is recommended. 4.Radiation therapy to the painful bony sites to ease/relieve symptoms with either one of the options is recommended: a.Single fraction i.e. radiation therapy at a dosage of 8 Gy for one fraction. Single fraction radiation should be repeated in future, as and when needed (i.e. when there is pain in the bones i.e. pain due to presence of cancer cells /lesions in the bones). OR This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 2 authority over the care of any individuals.

3. b.30 Gy in 10 fractions OR c.20 Gy in 5 fractions 5.Given bone metastases, bisphosphonate therapy with Zoledronic acid 4 mg or Denosumab 120 mg every four to six weeks is recommended. If your treatment plan involves complex details such as a choice of immunotherapy vs targeted therapy or enrollment in a clinical trial or bone marrow transplant, etc., please write to us at reports@navya.care We will prioritize a response based on clinical urgency as it pertains to your receiving on time care. Questions on managing ongoing side effects of cancer treatments such as pain, mouth sores, fever, infection, bleeding, etc. are only suited for in person examination with your local treating oncologist(s)/physician(s). These questions are not amenable to an online expert review. Navya is focused on assessing your cancer treatment options. If you are a financially underprivileged patient or receiving treatment under the General Category of any hospital, please reach out to us after you complete your current therapies (surgery or chemotherapy or radiation, etc.) We will assess your treatment response and continue to provide your next treatment plans at no cost. Please do not hesitate to write to us or call us with any questions. Sincerely, Gitika Srivastava This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 3 authority over the care of any individuals.

4. CASE SUMMARY Expert Opinion ID Current Diagnosis Metastatic Renal Cell Carcinoma Age 63 Years Old Gender Male Alcohol Yes [On socio weekends only, quit recently] Hypertension (High BP) Yes Chlorthalidone, Nebivolol, Indapamide] [On Telmisartan, Complaint(s) Cough, SOB and weight loss for the past 2-3 month [April 2020] Covid- 19 Negative [May 2020] Bronchoscopy Normal [April 30th 2020] Cytology BAL fluid- No e/o malignancy [April 30th 2020] Thyroid Panel Normal [April 21st 2020] Hepatitis Panel Negative [April 24th 2020] FDG- PET CT 7.7*7.6.6*6.7 cm Rt kidney lesion (SUV- 9.1) - suggestive of primary mitotic pathology. Multiple, b/l lung miliary nodules - s/o diffuse pulmonary mets; Multiple, prevascular, subaortic, subcarinal and b/l hilar mediastinal LNs (SUV- 9.9)- lymphatic mets; Bulky b/l adrenal glands- s/o mets. Multiple FDG avid osseous lesions involving the b/l humeri, b/l scapulae, b/l clavicles, sternum, b/l ribs, vertebrae, sacrum,b/l pelvic bones and b/l femora- mets [May 22nd 2020] This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 4 authority over the care of any individuals.

5. Met : Bone Yes Met : Lung Yes Met : CEA Adrenal Gland Yes 0.67 [May 2nd 2020] CA19.9 13.60 [May 2nd 2020] PSA 3.21[May 2nd 2020]​ Transbronchial Biopsy Focal e/o ?reactive atypia in lining epithelium. Suboptimal biopsy [May 7th 2020] Diagnosis Made By Biopsy- Right Kidney mass [May 28th 2020] Malignant Disease Carcinoma Diagnosis Made By Slide/Block Review- Right Kidney mass [June 1st 2020] Malignant Disease Renal Cell Carcinoma- Clear Cell Type IHC- Positive PAX-8, (Strong,diffuse),CK-7, CK-20 (focal) CA IX, CD10 IHC- Negative c-kit LDH 1610 [May 2020] Risk Stratification Intermediate (per MSKCC prognostic model) Note Started on injection Denosumab 120mg once a month Clinical TNM Stage Stage IV - Any T Any N M1 Bone Marrow (Hematologic) Function Adequate [May 23rd 2020] This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 5 authority over the care of any individuals.

6. Hb 13.4 Plt 348 DLC Neutrophils- 6.4 Kidney (Renal) Function Adequate [May 23rd 2020] Serum Uric Acid 7.40 Creatinine 1.26 Liver (Hepatic) Function Adequate [May 23rd 2020] ALT 46.00 Heart (Cardiac) Function Not Available Functional Status- ECOG Score 1 Karnofsky performance status 80% General Condition C/o pain and stiffness radiating from lower back to the lower extremities, cough when talking continuously, Wt loss (5 kgs in two months). However, he is able to care for self, can bathe, can clothe, can walk and carry all independent activities without any assistance. Resource Constraint No This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 6 authority over the care of any individuals.

7. Navya is a Cambridge, MA based company with offices in Bangalore, India. Navya is founded by graduates of Harvard University, MIT Sloan School of Management, and the Stanford School of Medicine. Navya’s innovative and scalable decision making system is a technology powered solution for complex medical questions. Navya’s software solutions are efficient engines to gather and synthesize individual goals of care, evidence specific to an individual medical case, and expert opinion, for evaluating treatment alternatives. Navya’s goal is to assist in bringing clarity to the complexity of evaluating treatment alternatives. Navya’s system collects the best available information and expertise from several worldwide sources relevant to a specific previously diagnosed medical case and assesses treatment decisions. For more information, please visit www.navya.care or call +91 80-61787700 or email gitika@navya.care Navya Network, Inc does not diagnose, prescribe medication, treat, or give orders, nor does Navya have the ultimate authority over the care of any individuals. Navya does not provide medical advice nor does its products, services, systems, projects, or programs constitute the practice of medicine, nursing, or any other health care profession. Any information provided by Navya as a result of use of Navya’s products, services, systems, projects, or programs is being provided solely for educational and informational benefit and should not be considered diagnosis, treatment or a substitute for professional medical advice. Use of Navya’s products, services, systems, projects, or programs does not establish a doctor-patient relationship. Navya Care encourages that individuals or patients using Navya’s products, services, systems, projects, or programs share any reports or other information generated by the use of Navya’s products, services, systems, projects, or programs with their treating health care provider. Use of Navya’s products, services, systems, projects, or programs is voluntary and any information communicated as a result of the use of Navya’s products, services, systems, projects, or programs is not intended to be, nor implied to be, and cannot and should not be used as a substitute for professional medical advice, diagnosis or treatment. Navya’s products, services, systems, projects, or programs are limited to the provision of consultative services with respect to known or previously-identified condition and neither Navya, nor its employees, consultants or agents with whom it contracts will diagnose, treat, give orders, prescribe medications or have any authority over the care of any individuals. Navya’s products, services, systems, projects, or programs will not involve any direct face-to-face encounters or physical examinations. Accordingly, individuals using Navya’s products, services, systems, projects, or programs are encouraged to share and discuss any information provided as a result of use of Navya’s products, services, systems, projects, or programs with their treating physician. The individuals or patients using Navya’s products, services, systems, projects, or programs will be the ultimate decision maker over their own care. This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 7 authority over the care of any individuals.

8. INDIVIDUALS OR PATIENTS USING NAVYA’S PRODUCTS, SERVICES, SYSTEMS, PROJECTS, OR PROGRAMS SHOULD NEVER DELAY OR AVOID SEEKING MEDICAL ADVICE OR ATTENTION FROM THEIR REGULAR HEALTH CARE PROVIDER OR TREATING PHYSICIAN OR DOCTOR BECAUSE OF SOMETHING THEY HAVE LEARNED THROUGH THEIR USE OF NAVYA’S PRODUCTS, SERVICES, SYSTEMS, PROJECTS, OR PROGRAMS. SHOULD ANY UNEXPECTED MEDICAL EVENT OCCUR WHILE AN INDIVIDUAL OR A PATIENT IS PARTICIPATING IN THE USE OF NAVYA’S PRODUCTS, SERVICES, SYSTEMS, PROJECTS, OR PROGRAMS, THE INDIVIDUAL OR THE PATIENT SHOULD IMMEDIATELY CALL THEIR HEALTHCARE PROVIDER OR TREATING PHYSICIAN OR DOCTOR OR LOCAL EMERGENCY ASSISTANCE NUMBER OR IMMEDIATELY VISIT THEIR LOCAL EMERGENCY ROOM. NAVYA AND ITS EMPLOYEES, CONSULTANTS, PARTNERS, AND EXPERTS ARE NOT AND SHALL NOT BE CONSTRUED AS BEING YOUR DOCTORS OR PHYSICIANS OR ONCOLOGISTS OR HEALTHCARE PROVIDERS FOR ANY PURPOSE WHATSOEVER. This TMC NCG Online Expert Opinion Service, and Navya Network Inc., does not diagnose, treat, give orders, or have the ultimate Page 8 authority over the care of any individuals.