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Table 1 BRCA1-mutated HGSOC patients receiving neoadjuvant therapy consisting of mitomycin C, doxorubicin and cisplatin

From: Neoadjuvant therapy of BRCA1-driven ovarian cancer by combination of cisplatin, mitomycin C and doxorubicin

ID

Age

Stage

BRCA1 mutation

Somatic BRCA1 status before NACT

MAP cycles

(NACT)

Surgical debulking

Response by RECIST

CRS (ovary / omentum)

Somatic BRCA1 status after NACT

ACT

(cycles)

TFI, months

PFS, months

OS, months

Toxicities and grades

TP53 mutation

MAP1

64

IIIC

c.5266dupC

LOH

3

Complete + HIPEC

PR (-44 %)

CRS 3 / no tumor cells in omentum

LOH

MAP (2)

25.4+

32.2+

32.2+

Anemia 1; nephrotoxicity 1

C135W

MAP2

35

IVA (pleuritis)

c.68_69delAG

LOH

3

Complete + HIPEC

PR (-73 %)

CRS 2 / no tumor cells in omentum

na

MAP (1), AT (2)

6.9

14.4

26.9

Anemia 1

R175H

MAP3

50

IIIC

c.4034delA

LOH

4

Complete

PR (-35 %)

CRS 2 / CRS 2

LOH

MAP (3)

23.6+

31.6+

31.6+

Anemia 1

Y234H

MAP4

57

IVB (lymph nodes)

c.5266dupC

LOH

3

Complete + HIPEC

PR (-90 %)

CRS 2 / CRS 3

Retention of the wild-type allele

AT (3)

29.2+

36.6+

36.6+

Diarrhea 1; emesis 1; gastritis 1; nausea 1; leukopenia 2; nephrotoxicity 2; thrombocytopenia 4

R213X

MAP5

50

IIIC

c.5266dupC

na

3

Complete

PR (-33 %)

CRS 2 / no tumor cells in omentum

LOH

MAP (3)

22.2+

29.5+

29.5+

Anemia 1; leukopenia 1; nausea 1; thrombocytopenia 1

c.97-1G > A

MAP6

45

IVB (spleen, lymph nodes)

c.1961delA

LOH

4

Suboptimal

PR (-47 %)

CRS 2 / CRS 2

LOH

TCbP (6)

21+

30.4+

30.4+

Anemia 1; nausea 1; thrombosis

R213X

MAP7

56

IVB (pleuritis, lymph nodes)

c.5266dupC

na

3

Complete

PR (-47 %)

CRS 2 / CRS 2

LOH

MAP (1)

4.1

8.3

29.8+

Anemia 2; nephrotoxicity 3

c.314delG

MAP8

58

IIIC

c.4034delA

LOH

5

Complete

PR (-46 %)

CRS 2 / CRS 2

LOH

TCbP (4)

11.5

20.7

28.2+

Anemia 1; neutropenia 2

R248Q

MAP9

46

IIIC

c.4034delA

LOH

4

Complete

PR (-64 %)

CRS 2 / CRS 2

LOH

MAP (2)

3.1

11.2

15.8

Thrombocytopenia 2

I255S

MAP10

40

IVB (pleuritis, lymph nodes)

c.5266dupC

LOH

4

Complete

PR (-36 %)

na / no tumor cells in omentum

na

None

28.5+

37.6+

37.6+

Anemia 1; hepatotoxicity 2; thrombocytopenia 2; nephrotoxicity 3

M133R

  1. ACT Adjuvant chemotherapy, AT Doxorubicin 60 mg/m2 and paclitaxel 175 mg/m2, every 3 weeks, CRS Chemotherapy response score, HIPEC hyperthermic intraperitoneal chemotherapy, LOH Loss of heterozygosity, na Not analyzed, MAP Mitomycin C 10 mg/m2 (day 1), doxorubicin 30 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1), given every 4 weeks, NACT Neoadjuvant chemotherapy, OS Overall survival, PFS Progression-free survival, PR Partial response, TCbP Paclitaxel 175 mg/m2 plus carboplatin (6 AUC), given every 3 weeks, TFI Treatment-free interval.
  2. Notes: Tumor responses presented in the table describe the status of patients observed after the completion of the NACT, i.e. straight before the surgery. Patient MAP10 was diagnosed with ovarian cancer upon surgery, which was performed in another hospital and was limited to the excision of ovaries. She was considered eligible for the NACT study, as she had a significant tumor burden and could not be subjected to primary debulking surgery; she received no adjuvant therapy, as no residual tumor cells was seen in the surgical material. Patient MAP4 demonstrated the restoration of heterozygosity in a post-NACT tumor sample, suggesting that the tumor may no longer be platinum-sensitive [8, 9]; based on this finding, combination of paclitaxel and doxorubicin was given after the surgery; similarly, this combination was incorporated in the adjuvant treatment for patient MAP2, where the molecular analysis of post-NACT tumor tissue failed to establish somatic BRCA1 status. Patients MAP6 and MAP8 received TCbP combination after the surgery due to preference of their primary physicians.
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Hereditary Cancer in Clinical Practice

ISSN: 1897-4287