Trials to learn!

Question 1

EMILIA trial?

Answer 1

2013 Phase III; compared T-DM1 with lapatinib plus capecitabine in women with HER-2 positive advanced (metastatic) breast cancer in women previously treated with trastuzumab. Found that T-DM1 prolonged OS, with less toxicity.

Question 2

KATHERINE trial?

Answer 2

2018; Phase III; looked at trastuzumab emtansine vs trastuzumab in HER-2 positive early breast cancer who had residual invasive disease after chemotherapy and trastuzumab. T-DM1 lowered risk of recurrence or death by 50%.

Question 3

Study that showed gefitinib worked?

Answer 3

2010, Maemondo. Firstline gefitinib vs chemotherapy in patients preselected for EGFR mutations improved PFS.

Question 4

COMET trial?

Answer 4

Ongoing; patients with low grade DCIS are randomised to either operative (BCS) or active surveillance.

Question 5

1 million study?

Answer 5

2012; outcomes of FOB testing. Found that 2% were positive and that 71% of cancers detected were early!

Question 6

Two county study?

Answer 6

Breast cancer; Sweden, 1985. Found that there would be 30% mortality reduction. Later revised to roughly 2% after follow up.

Question 7

Forrest report?

Answer 7

1986; after Swedish two county - looked at QALYs of introducing breast screening. Did not consider morbidity re overdiagnosis and was later amended to reflect this.

Question 8

Cochrane review for breast screening?

Answer 8

2011; suggested that overdiagnosis was 30% and that mortality reduction was actually 15%, not the feted 30% of Two-county

Question 9

Marmot review?

Answer 9

For breast cancer; 2017. Found 20% mortality reduction, 1 death prevented for every 250 invites. 1/4 diagnosed are OVERDIAGNOSED. Means for every 1,000 screened, 5 lives saved and 17 overdiagnosed

Question 10

Trials of olaparib and chemotherapy?

Answer 10

Phase II, Plummer, 2006. With TMZ in metastatic melanoma. Had high myelosuppression so dropped down. Single agent dose from Phase I stupidly taken forward (RP2D). Not continued to Phase III; partially because other treatments changed for melanoma and single agent PARP more commonly used.

Question 11

SOLO1? And SOLO2?

Answer 11

Olaparib maintenance MONOtherapy vs placebo in BRCA-mutant, firstline Pt-sensitive advanced ovarian cancer vs placebo. 2018. Lowered risk of progression. SOLO2 looked at same patient demographics but in relapsed disease. Both improved PFS.

Question 12

PRIMA study?

Answer 12

Niraparib vs placebo in ovarian cancer, advanced, Phase III, post response to platinum, maintenance. Do not need BRCA mutation! Ongoing

Question 13

Study that led to olaparib licensing for monotherapy?

Answer 13

Phase II, randomised, Ledermann, 2012, olaparib vs placebo for relapsed platinum sensitive high grade serous ovarian cancer. Improved PFS!

Question 14

Other PARP study with chemotherapy?

Answer 14

Thaker et al, 2017, in cervical cancer, Phase I of velaparib with paclitaxel and cisplatin in persistent/recurrent cervical cancer

Question 15

Iniparib trials?

Answer 15

Poorly designed Phase II trials in breast cancer; first PARP to make to phase III. 2011 study in TNBC, published in NEJM. Iniparib and platinum chemotherapy vs placebo and chemotherapy. Improved OS. Trial flawed because placebo patients could move over. Expanded Phase III trial showed no statistically significant improvement.

Question 16

HERA trial?

Answer 16

2005; was for trastuzumab 1 year vs 2 years vs observation in HER-2 positive early breast cancer after all primary therapy. Trastuzumab significantly improved DFS, but 1 year was equal to 2. Continued follow up showed that these effects were durable after 11 years.

Question 17

BOLERO-2?

Answer 17

Trial of exemestane and everolimus (mTOR inhibitor) for metastatic breast cancer after relapse on an aromatase inhibitor) versus exemestane and a placebo in post menopausal, hormone receptor positive women. 2012. Found that improved PFS.

Question 18

Trial for bevacizumab in CRC?

Answer 18

2004 Hurwitz; showed how in metastatic CRC adding bevacizumab to 5-FU, leucovorin and irinotecan vs placebo in Phase III improved OS.

Question 19

Trial for ramuciramab in CRC?

Answer 19

2015, Tabernero; RCT Phase III of this vs placebo in combination with second line FOLFIRI in patients with metastatic CRC after failure of bevacizumab. Targets VEGF receptor II.

Question 20

EBCTCG for BCS?

Answer 20

1985; for BCS with radiotherapy vs BCS alone; found that radiotherapy improved mortality rates and reduced local recurrence.

Question 21

Trial for timing of tamoxifen (EBCTCG)?

Answer 21

2005: showed that 5 years tamoxifen vs 2 years in the adjuvant setting led to reduced mortality rate.

Question 22

Trial for tamoxifen vs AI in post menopausal?

Answer 22

EBCTG again. 2015. Showed that had improved survival with 5 years of AI in post menopausal.

Question 23

Trial for adjuvant vs neoadjuvant chemotherapy in breast cancer?

Answer 23

EBCTCG; 2018; showed that no effect on mortality. Neo predictably lead to more BCS; but slightly higher LRR.

Question 24

Trial for ovarian ablation in breast cancer?

Answer 24

2000; EBCTCG. Showed that in early breast cancer, that had not been treated with chemotherapy, ablation (obviously in premenopausual women) increased survival

Question 25

BRIM3 study?

Answer 25

2014; vemurafenib (BRAF inhibitor) vs dacarbazine; RCT in patients with metastatic melanoma and BRAF mutations. BRAFi improved OS. Similar findings in BREAK-3 for dabrafenib

Question 26

BRAF/MEK inhibitors?

Answer 26

2014 study used BRAFi and MEK inhibitor vs BRAFi and placebo; found that survival was increased (Robert et al.)

Question 27

Trial for combining BRAF/MEK and PDL1?

Answer 27

One of the early trials was 2017, Sullivan et al, in ASCO, with metastatic melanoma with BRAF mutations, 1b trial showed manageable safety and promising antitumour activity. Subsequent Phase III trial randomising patients with the BRAF/MEk to either PDL1 or placebo is ongoing.

Question 28

Trial for combining BRAF/MEK and PDL1?

Answer 28

One of the early trials was 2017, Sullivan et al, in ASCO, with metastatic melanoma with BRAF mutations, 1b trial showed manageable safety and promising antitumour activity. Subsequent Phase III trial randomising patients with the BRAF/MEk to either PDL1 or placebo is ongoing.