Durvalumab after concurrent chemotherapy and high-dose radiotherapy for locally advanced non-small cell lung cancer

Figures & data

Table 1. Baseline characteristics of 39 patients with stage III NSCLC

Characteristic	Value
Sex (male)	25 (64%)
Age (y), median (range)	66.5 (48.8–85.1)
Performance status
ECOG 0	9 (23%)
ECOG 1	30 (77%)
Smoking history (yes)	33 (85%)
Histology
Non-squamous	28 (72%)
Squamous	11 (28%)
Stage
IIIA	27 (69%)
IIIB	12 (32%)
PDL1 expression TPS
>1%	18 (46%)
<1%	11 (28%)
Unknown	10 (26%)
Driver mutation status (only EGFR or ALK alterations)
Yes	3 (8%)
No	26 (66%)
Unknown	10 (26%)

NSCLC, non-small cell lung cancer; ECOG, Eastern Cooperative Oncology Group [score]; PDL1, programmed death ligand 1; TPS, tumor proportion score; EGFR, epidermal growth factor receptor; ALK, anaplastic lymphoma kinase.

Table 2. Treatment of 39 patients with stage III NSCLC

Treatment parameter	Value
Radiation dosimetrics, mean ± SD
Dose (Gy)	69.9 ± 3.1
GTV (cc)	118.2 ± 95.8
Lung V5 (%)	45.7 ± 15.1
Lung V20 (%)	21 ± 9.4
MLD (Gy)	12.2 ± 4.6
Heart V5 (%)	20.7 ± 2.7
Heart V20 (%)	4.2 ± 6
MHD (Gy)	5 ± 5.5
Type of chemotherapy:	n (%)
Cisplatin doublet	25(64%)
Carboplatin doublet	13(33%)
No chemotherapy	1(3%)
Response to chemoradiotherapy
Complete response	7 (18%)
Partial response	30 (77%)
Stable disease	2 (5%)
Durvalumab therapy
Months to initiation, median (range)	2.2 (0.6–5.3)
Number of cycles, median (range)	21 (1–26)
Duration of therapy, months, median (range)	10.4 (0.5–15.6)
Completed a full year	17(44%)
Reason for durvalumab discontinuation
Disease progression	12 (31%)
Immune-related toxicity	7 (18%)
Patient preference	2 (5%)
Death from other causes	2 (5%)

Values are presented as n(%), unless otherwise stated.

GTV, gross tumor volume, V5, lung volume receiving at least 5 Gy;

V20, lung volume receiving at least 20 Gy, MLD, mean lung dose;

MHD, mean heart dose.

Table 3. Univariate analysis of patient and treatment parameters and survival outcomes

Characteristic	N (%) Unless otherwise specified	PFS				OS
		HR	P-value	CI LL	CI UL	HR	P-value	CI LL	CI UL
Age, y, median (range)	66.5 (48.8–85.1)	1.01	0.78	0.96	1.06	1.05	0.18	0.98	1.13
Sex
Male	25 (64%)	1.00				1.00
Female	14 (36%)	1.45	0.40	0.61	3.45	1.37	0.59	0.43	4.34
Performance status
ECOG 0	9 (23%)	1.00				1.00
ECOG 1	30 (77%)	1.81	0.29	0.61	5.38	1.89	0.41	0.41	8.71
Smoking history
No	6 (15%)	1.00				1.00
Yes	33 (85%)	0.94	0.92	0.32	2.82	0.99	0.99	0.21	4.53
Histology
Non-squamous	28 (72%)	1.00				1.00
Squamous	11 (28%)	1.78	0.20	0.73	4.33	2.11	0.21	0.66	6.77
Stage
IIIA	27 (69%)	1.00				1.00
IIIB	12 (32%)	1.99	0.13	0.82	4.82	1.36	0.62	0.41	4.54
Primary side
Right lung	25 (64%)	1.00				1.00
Left lung	11(28%)	0.74	0.54	0.29	1.92	0.65	0.51	0.17	2.40
Midline	3(8%)
PDL1 expression
>1%	18 (46%)	1.00
<1%	11 (28%)	1.08	0.88	0.38	3.06	2.33	0.30	0.47	11.55
Unknown	10 (26%)
Driver mutation status (only EGFR or ALK alterations)
No	26 (66%)	1.00				1.00
Yes	3 (8%)	1.25	0.77	0.28	5.56	1.49	0.71	0.18	12.45
Unknown	10 (26%)
Type of chemotherapy
Cisplatin doublet	25(64%)	1.00				1.00
Carboplatin doublet	13(33%)	0.79	0.63	0.31	2.04	1.63	0.41	0.52	5.14
No chemotherapy	1(3%)
Durvalumab therapy
Months to initiation, median (range)	2.2 (0.6–5.3)	0.68	0.11	0.43	1.09	1.00	0.99	0.52	5.14
Number of cycles, median (range)	21 (1–26)	0.86	<0.001	0.81	0.91	0.83	<0.001	0.76	0.91
Immune-related G3+ toxicity occurrence
No	29 (74%)	1.00				1.00
Yes	10 (26%)	1.45	0.45	0.56	3.75	2.38	0.18	0.67	8.48

Figure 1. Kaplan–Meier graphs of PFS (a) and OS (b) and a competing risks graph of LRF (c) with 95% confidence intervals. The competing risk for LRF is death

Table 4. Reported adverse events in 39 patients with stage III NSCLC during durvalumab therapy

Adverse event	Value
Fatigue	30 (77%)
Dyspnea	28 (72%)
Endocrine changes	18 (46%)
Hepatitis	14 (36%)
Diarrhea	5 (13%)
Nausea	4 (10%)
Patients with any grade 3–5 adverse event	14 (36%)
Immune related
Pneumonitis	6 (15%)
Hepatitis	2 (5%)
Arthralgia	1 (3%)
Pericarditis	1 (3%)
Immune-related mortality – 1(3%) grade 5 pneumonitis
Nonimmune related
Pneumonia 2 – grade 3 Anemia 1 – grade 3 Acute myocardial infarction 1 – grade 5 Massive hemoptysis 1 – grade 5

Table 5. Patterns of failure

Failure patterns	N	%
Alive without progression	18	46.2
Dead without progression	4	10.3
Site of first progression
Intrathoracic	8	20.5
In-field	4	10.3
Out-of-field	4	10.3
Extrathoracic	9	23.1
Brain	5	12.8
Liver	2	5.1
Lymph nodes	2	5.1
Bones	2	5.1
Combined	3	7.7
Total out-of-field failures	13	33.4
Total in-field failures (including later progression)	6	15.4