Table 1 Selected trials of BRAF and MEK inhibitors

From: BRAFV600E-mutant metastatic NSCLC: disease overview and treatment landscape

Treatment

Mutation status

Patients, n

Median follow-up, mo

ORR (CR/PR), %

Median DOR, mo

Median time to response, mo

Median PFS, mo

Median OS, mo

Safety

Interruption, reduction, and permanent discontinuation, %a

Ref

BRAF Inhibitor Monotherapy

Vemurafenib

V600E (90%), V600G (5%), unknown V600 (5%)

20b (treatment-naive and previously treated)

NA

42 (0/42)

NA

NA

7.3

NE

Grade 3/4 AEs: 80%

Common any-grade AEs: decreased appetite (35%), nausea (35%), dyspnea (30%), hyperkeratosis (30%), vomiting (30%)

NA

55

Vemurafenib

V600E (98%), unspecified V600 (2%)

8 (treatment-naive)

10.7

37.5 (0/38)

NE

NE

12.9

NE

Grade 3/4 AEs: 77%

Common any-grade AEs: nausea (40%), hyperkeratosis (34%), decreased appetite (32%), arthralgia (31%)

40, 61, 10

66

54 (previously treated)

10.7

37.0 (0/37)

6.1

7.3

6.1

15.4

Vemurafenib

V600E (96%), V600K (2%), V600D (1%), V600M (1%)

101 (previously treated)

23.9

44.8 (NA/NA)c

6.4

NA

5.2

10

SAEs: 36%

Common any-grade TRAEs: asthenia (56%), decreased appetite (46%)

NA, NA, 24

11

Dabrafenib

V600E

6 (treatment-naive)

NA

67 (0/67)

NA

NA

NA

NA

Grade 3/4 AEs: 44%

Common any-grade AEs: pyrexia (36%), asthenia (30%), hyperkeratosis (30%), decreased appetite (29%), nausea (27%), cutaneous SCC (12%)

43, 18, 6

10

78 (previously treated)

10.7

33 (NA/NA)

9.6

NA

5.5

12.7

BRAF and MEK Inhibitor Combination Therapies

Dabrafenib plus trametinib

V600E

36d (treatment-naive)

15.9

64 (6/58)

10.4

NA

10.9

24.6

Grade 3/4 AEs: 69%

Common any-grade AEs: pyrexia (64%), nausea (56%), diarrhea (36%), fatigue (36%), peripheral edema (36%), vomiting (33%), dry skin (33%), decreased appetite (33%)

75, 39, 22

16

Dabrafenib plus trametinib

V600E

57e (previously treated)

11.6

63.2 (3.5/59.6)

9.0

1.4f

9.7

NE

Grade 3/4 AEs: 49%

Common any-grade AEs: pyrexia (46%), nausea (40%), vomiting (35%), diarrhea (33%), asthenia (32%), decreased appetite (30%), cutaneous SCC (4%)

61, 35, 12

15

Encorafenib plus binimetinib

(PHAROS)

V600Eg

59 (treatment-naive)

18.2h

75 (15/59)

NE

1.9

NE

NE

Grade 3/4 TRAEs: 41%

Common any-grade TRAEs: nausea (50%), diarrhea (43%), fatigue (32%), vomiting (29%)

All-causality pyrexia (22%)

44, 24, 15

18

39 (previously treated)

12.8h

46 (10/36)

16.7

1.7

9.3

NE

  1. AE adverse event, CR complete response, DOR duration of response, NA not available, NE not estimable or not reached, ORR objective response rate, OS overall survival, PFS progression-free survival, PR partial response, SAE serious AE, SCC squamous cell carcinoma, TRAE treatment-related AE.
  2. aDose interruption, dose reduction, and permanent treatment discontinuation due to AEs.
  3. bEfficacy and safety were analyzed for 19 patients. However, one patient dropped out prior to assessment of response and was included in the denominator for efficacy but as having no response.
  4. cORR was analyzed for 96 patients.
  5. dUpdated 5-year analysis reported ORR of 63.9%, median PFS of 10.8 months, and median OS of 17.3 months17.
  6. eUpdated 5-year analysis reported ORR of 68.4%, median PFS of 10.2 months, and median OS of 18.2 months17.
  7. fMedian time to response was reported as 6 weeks in the paper. Weeks to months was calculated with 1:0.23 conversion.
  8. gOne previously treated patient had both V600D and V600E mutations in their tumor.
  9. hMedian duration of follow-up for this study was for PFS.
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