Among the trials reviewed in 2016: 1) A study of grade 2 gliomas in young patients found that progression-free survival and overall survival were longer for those who received radiation therapy plus chemotherapy compared to radiation therapy alone. 2) A prostate cancer study found that among men with localized prostate cancer, survival was similar for those undergoing surveillance with PET-CT scans compared to planned neck dissection, but surveillance resulted in fewer operations and was more cost-effective. 3) A soft-tissue sarcoma study found that overall survival was improved for patients receiving eribulin compared to an active control, suggesting eribulin could be a new treatment option for advanced soft-tissue sarcoma.

1. Dr. Vibhay Pareek
Dr. Rajendra Bhalavat
Dr. Manish Chandra
Radiation Oncology
Important Trials of 2016:
A Year in Review

2. Radiation and PCV in Low grade Glioma

4. • Grade 2 Gliomas in young patients: RT + PCV vs RT Alone
• 251 eligible patients
• Median follow up 11.9 years
• Radiation dose 54Gy in 28fr (1.8Gy)
• Chemotherapy:
• 6 cycles of procarbazine (60mg/m2) orally on days 8 through 21
• CCNU (110 mg/m2) orally day 1 of each cycle
• Vincristine (1.4 mg/m2) i.v on days 8 and 29 of each cycle
• Cycle length 8 weeks
• MMSE evaluation and follow up

6. • PFS: 10.4 vs 4 years in RT + Chemo vs RT Alone
• Rate of PFS at 5 yrs: 61% vs 44%
• At 10 yrs: 51% vs 21%
• IDH1 R132H – longer PFS
• Overall survival: 13.3 vs 7.8 years
• At 5 years: 72 vs 63%
• At 10 years: 60 vs 40%
• Toxicities greater with RT + Chemotherapy arm
In a cohort of patients with grade 2 glioma who were younger than 40
years of age and had undergone subtotal tumor resection or who were 40
years of age or older, progression-free survival and overall survival were
longer among those who received combination chemotherapy in addition
to radiation therapy than among those who received radiation therapy
alone.

7. PROTECT Trial

9. • 1999 – 2009
• 82,429 – 2664 diagnosed with localized prostate cancer
• 1643 patient:
• 545 – active monitoring
• 553 – surgery
• 545 – radiotherapy
Follow up median period: 10 years
Primary end point: Prostate cancer mortality

12. Sarcoma: Role of Chemotherapy

14. • Phase 2 study
• Activity and tolerability of eribulin in advanced or metastatic STS
• In this phase 3 study, aimed to compare overall survival in patients with
advanced or metastatic soft-tissue sarcoma who received eribulin with
that in patients who received dacarbazine (an active control)
• Patients aged 18 years or older with intermediate-grade or high-grade
advanced liposarcoma or leiomyosarcoma who had received at least two
previous systemic regimens for advanced disease (including an
anthracycline)
• The primary endpoint was overall survival in the intention-to-treat
population

15. • Overal survival in Eribulin arm better (13.5 vs 11.5 months)
• Grade 3 or higher toxicities were more in eribulin arm
• Overall survival was improved in patients assigned to eribulin compared
with those assigned to an active control, suggesting that eribulin could be
a treatment option for advanced soft-tissue sarcoma

16. Trabectedin demonstrates superior disease control versus conventional dacarbazine in
patients who have advanced liposarcoma and leiomyosarcoma after they experience failure
of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant
end point, this study supports the activity of trabectedin for patients with these malignancies

17. This study of olaratumab with doxorubicin in patients with advanced soft-tissue sarcoma met
its predefined primary endpoint for progression-free survival and achieved a highly
significant improvement of 11·8 months in median overall survival, suggesting a potential
shift in the treatment of soft-tissue sarcoma.

18. PET Neck Trial

20. • 564 patients – 282 each in planned surgery and surveillance group
• N2a – 17%; 61% - N2b; 84% - Oropharyngeal disease
• Median follow up – 36 months
• PET CT guidance – fewer neck dissections than planned (54 vs 221)
• Similar rates of surgical complications
• 2 yr OS: 84.9 vs 81.5% - Surveillance vs planned Surgery
• Hazard ratio related to death slightly favoured PET CT guided surveillance
• QoL similar in both groups
• Savings of 1492 pounds in PET CT surveillance group
Survival was similar among patients who underwent PET-CT–guided
surveillance and those who underwent planned neck dissection, but
surveillance resulted in considerably fewer operations and it was more
cost-effective.

21. Role of Radiosurgery in Brain Metastases

22. Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS
combined with WBRT, resulted in less cognitive deterioration at 3 months. In the
absence of a difference in overall survival, these findings suggest that for patients with
1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred
strategy.

23. The year of Nivolumab ……….

25. • Nivolumab vs Methotrexate, Docetaxel or Cetuximab
• Primary end point – overall survival
• Additional end points – PFS, objective response, safety, QoL
• Median overall survival – 7.5 vs 5.1 months
• 1 year survival rates were 19% higher with Nivolumab
• PFS at 6 months – 19.7 vs 9.9%
• Response rate – 13.3 vs 5.8%
• Toxicities – 13.1 vs 35.1%
• Physical, role and social functioning scores were better
Among patients with platinum-refractory, recurrent squamous-cell
carcinoma of the head and neck, treatment with nivolumab resulted
in longer overall survival than treatment with standard, single-agent
therapy

26. …… however in Metastatic NSCLC

27. Nivolumab did not show superior PFS compared to IC PT-DC as first-line
therapy in stage IV/recurrent NSCLC patients with ≥5% PD-L1 tumor
expression.
The safety profile of nivolumab was favorable to IC PT-DC and consistent
with previous studies.
Nivolumab plus ipilimumab and nivolumab plus chemotherapy are being
evaluated in a phase 3 trial in previously untreated NSCLC (CheckMate
227).

28. In patients with advanced NSCLC and PD-L1 expression on at least
50% of tumor cells, pembrolizumab was associated with significantly
longer progression-free and overall survival and with fewer adverse
events than was platinum-based chemotherapy.

29. Osimertinib had significantly greater efficacy than platinum therapy plus
pemetrexed in patients with T790M-positive advanced non–small-cell
lung cancer (including those with CNS metastases) in whom disease had
progressed during first-line EGFR-TKI therapy.

30. JASPAC 01 trial for resected Pancreatic Cancer

31. • Overall survival improved by 21 months
• 5 year overall survival: 44.1 vs 24.1%
• Decreased toxicities in S – 1 arm compared to gemcitabine arm

32. • Median survival was 28 months vs 25.5 months for GEM/CAP vs
GEM alone
• Toxicities were more in the GEM/CAP arm
• Adjuvant GEM/CAP for pancreatic cancer had statistically
significant improvement in survival compared to GEM
monotherapy

33. Newer agents in Renal Cell Carcinoma

34. • Median Follow up was 19 months
• Median overall survival: 21.4 vs 16.5 months
• Improved progression free survival and objective response with
cabozantinib
• Grade 3 or 4 toxicities were equal in both groups
• Median overall survival with nivolumab was 25 months vs 19.6 with
everolimus
• Grade 3 or 4 toxicities, progression free survival and objective
response better with nivolumab
• Among patients with previously treated advanced renal-cell carcinoma, overall
survival was longer and fewer grade 3 or 4 adverse events occurred with
nivolumab than with everolimus.
• Treatment with cabozantinib increased overall survival, delayed disease
progression, and improved the objective response compared with everolimus.
Based on these results, cabozantinib should be considered as a new standard-of-
care treatment option for previously treated patients with advanced renal cell
carcinoma. Patients should be monitored for adverse events that might require
dose modifications.

35. Cabozantinib demonstrated a significant clinical benefit in PFS and ORR over
standard-of-care sunitinib as first-line therapy in patients with intermediate-
or poor-risk mRCC.

36. Antiemetics for Chemotherapy induced emesis

37. • The proportion of patients with no chemotherapy-induced nausea was significantly
greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74%
vs. 45%, P=0.002)
• The period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the
overall 120-hour period (37% vs. 22%, P=0.002).
• The complete-response rate was also significantly increased with olanzapine during the
three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus
41% (P<0.001), respectively.
• Although there were no grade 5 toxic effects, some patients receiving olanzapine had
increased sedation (severe in 5%) on day 2.
Olanzapine, as compared with placebo, significantly improved nausea
prevention, as well as the complete-response rate, among previously untreated
patients who were receiving highly emetogenic chemotherapy.

38. MINDACT Trial

39. • Among women with early-stage breast cancer who were at high
clinical risk and low genomic risk for recurrence, the receipt of no
chemotherapy on the basis of the 70-gene signature led to a 5-year
rate of survival without distant metastasis that was 1.5 percentage
points lower than the rate with chemotherapy.
• Given these findings, approximately 46% of women with breast
cancer who are at high clinical risk might not require chemotherapy.
• The MINDACT study assessed the utility of Mammaprint in deciding
whether or not to use chemotherapy in patients with early breast cancer
• found that when clinical risks (C-R) and genomic risks (G-R) are
discordant, women could avoid taking chemotherapy if their G-R is low
despite high C-R
• This trial also showed that if the C-R is low, there is no added
advantage of chemotherapy just because the G-R is high.

40. Extending Aromatase-Inhibitor Adjuvant Therapy
to 10 Years – Do we really need it?

42. • 1918 women
• Median follow up 6.3 years
• 165 – disease recurrence or CBC (67 – Letroz; 98 with placebo) and 200
deaths (100 in each group)
• 5 yr DFS – 95% vs 91%
• 5 yr OS – 93% vs 94%
• Bone related toxicities more with letrozole
• No difference in quality of life
The extension of treatment with an adjuvant aromatase inhibitor to
10 years resulted in significantly higher rates of disease-free
survival and a lower incidence of contralateral breast cancer than
those with placebo, but the rate of overall survival was not higher
with the aromatase inhibitor than with placebo.

43. Miscellaneous Trials

44. • MAG-A3 in NSCLC
• Nivolumab in stage IV/ recurrent NSCLC
• IMA901 with sunitinib in mRCC – IMPRINT Trial
• Iplimumab with chemotherapy drugs in extensive stage small cell lung
cancer
Failures of Immunotherapies in 2016

45. Among women with ERBB2-positive metastatic breast cancer
receiving taxanes, the use of a proposed trastuzumab biosimilar
compared with trastuzumab resulted in an equivalent overall
response rate at 24 weeks.
Further study is needed to assess safety and long-term clinical
outcome

46. Among patients with platinum-sensitive, recurrent ovarian cancer, the
median duration of progression-free survival was significantly longer
among those receiving niraparib than among those receiving placebo,
regardless of the presence or absence of gBRCA mutations or HRD
status, with moderate bone marrow toxicity.

47. • RADIANT-4 trial – Everolimus in neuroendocrine tumors
• TERRAIN and STRIVE trial – Enzalutamide vs Bicalutamide
• GOG 262 – Dose dense Palcitaxel in ovarian cancer
• Iplimumab in Stage III Melanoma
• Atezolizumab in Urothelial cancers
Others ….. With questionable significance

48. Thank You ……