Complete response to durvalumab consolidation in a patient with unresectable stage III PD-L1–negative NSCLC

Presentation and investigation
A 60-year-old nonsmoking female presented with mild cough in 2023. Apart from hypertension and a history of lung cancer in her father, she was phys­ically fit with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0.

PET-CT in November 2023 showed a large mass of 6.7 cm in the right up­per lobe of the lung, closely encroaching the chest wall and pleura, with multiple mediastinal lymph nodes (LNs) in sta­tions 2R and 4R, 7R, 10R, and11R, and a small right supraclavicular node, consistent with N3 disease.¹ (Figure 1A) Several small LNs were also noted in the left neck and axilla; these were speculat­ed to be reactive, likely related to recent Streptococcus pneumoniae vaccina­tion. Brain MRI was negative.

CT-guided biopsy revealed adeno­carcinoma. Genetic testing (LCMAP) detected HER2 exon 20 insertion muta­tion, with no EGFR mutation identified. SP263 assay demonstrated PD-L1 ex­pression of 0 percent. Her tumour mark­ers were elevated, including CA-125 (200 U/mL), CEA (21.1 ng/mL), and CA 19-9 (187 U/mL). The patient was diag­nosed with stage IIIC (T3N3) non-small-cell lung cancer (NSCLC) based on the 8th edition of American Joint Committee on Cancer (AJCC) staging manual.¹

Treatment, response and tolerability
After a multidisciplinary meeting, the PACIFIC regimen (ie, chemoradio­therapy [CRT] followed by durvalumab consolidation) was recommended as first-line treatment, with HER2-targeted therapy reserved for metastatic disease.

From 11 December 2023 to 19 January 2024, the patient received six weekly cycles of platinum-based che­motherapy with paclitaxel and carbo­platin, concurrently with radiotherapy (60 Gy), to cover the primary tumour and regional LNs.

Concurrent CRT (cCRT) was well tolerated. CT of the thorax on in Feb­ruary 2024 showed tumour shrinkage from 6.7 to 3.3 cm, with good response in all regional LNs. Levels of all tumour markers had also normalized (CA-125, 13 U/mL; CEA, 1.8 ng/mL; CA 19-9, 15 U/mL).

On 20 February 2024, 1 month after completing cCRT, intravenous durvalumab at 10 mg/kg Q2W was initi­ated per protocol as consolidation ther­apy for up to 12 months.

The patient experienced two types of immune-related adverse events (irAEs). She initially developed transient thyroid­itis in March 2024, which progressed to hypothyroidism after 2 months. Low-dose thyroxine replacement was initi­ated in May 2024. In November 2024, after 8 months of durvalumab consoli­dation, CT showed new ground-glass densities in the left upper and lower lobes (outside the radiation field), sus­pected to be interstitial lung disease (ILD). The patient was asymptomatic (grade 1), but durvalumab was withheld for 1 month. As she remained clinical­ly stable and asymptomatic, with no progression on follow-up CT scan of thorax, durvalumab was restarted, and 12-month consolidation was completed in February 2025.

The patient achieved complete re­sponse, with clearance of the primary tumour and all LNs. Restaging PET-CT in March 2025 showed no active dis­ease, although there was a tiny lesion at the primary tumour site, which was most likely radiation-induced inflamma­tion rather than tumour, as it showed progressive improvement over time. (Figure 1B) Her ECOG PS remained 0 with a good quality of life throughout treatment.

As of November 2025, the patient remained clinically well, with normal levels of biomarkers and no active dis­ease. Follow-up brain MRI was nega­tive, and PET-CT demonstrated further improvement of the small inflammatory lesion, with decreased size and tracer uptake. Thyroxine replacement contin­ued. At the time of writing, the patient’s progression-free survival (PFS) and overall survival (OS) were ≥21 months and ongoing.

Discussion
According to the 2025 European Society for Medical Oncology (ESMO) guidelines, 1 year of durvalumab consol­idation is recommended for patients with unresectable, EGFR–wild-type, stage III NSCLC who have not experienced disease progression after cCRT (level of evidence, I; grade of recommendation, A), including our patient. This high level of recommendation is based on the PA­CIFIC trial, which established durvalum­ab consolidation following cCRT as a standard of care.²

In the phase III PACIFIC trial, 713 pa­tients with unresectable stage III NSCLC were randomized 2:1 to receive either durvalumab (10 mg/kg intravenously) or placebo Q2W for up to 12 months. The study drug was administered 1–42 days after the patients received cCRT.³

Exploratory survival analyses of PA­CIFIC demonstrated robust and sus­tained OS and durable PFS benefits with durvalumab. At 5 years, durvalum­ab consolidation improved both OS (42.9 vs 33.4 percent) and PFS (33.1 vs 19.0 percent) vs placebo in the intention-to-treat population.⁴

Durvalumab consolidation in patients with PD-L1 <1 percent?
An important question was wheth­er to use durvalumab consolidation for our PD-L1–negative patient. Notably, durvalumab is the only immunotherapy recommended for post-cCRT consol­idation in patients with unresectable stage III NSCLC, including those with PD-L1 expression <1 percent. Both the 2024 American Society of Clinical On­cology (ASCO) Guideline Rapid Recom­mendation Update and the 2025 Asian Thoracic Oncology Research Group ex­pert consensus statement consistently recommend durvalumab consolidation after cCRT in patients with unresect­able, EGFR- and ALK-negative, stage III NSCLC regardless of PD-L1 expression levels.^5,6

In a real-world setting, the 5-year PACIFIC-R study (n=1,153) showed encouraging PFS and OS results with post-CRT durvalumab consolidation across subgroups, irrespective of PD-L1 expression levels.⁷ (Figure 2) This is consistent with the experience of our PD-L1–negative patient, who achieved a complete response to durvalumab after cCRT, with PFS and OS of ≥21 months.

Prespecified subgroup analyses of the PACIFIC trial also demonstrat­ed durvalumab’s PFS benefit across PD-L1 expression levels.⁴ (Figure 3) Although there was no OS benefit in patients with PD-L1 expression <1 per­cent, the results may be limited by the relatively small number of patients in this subgroup (n=148) and by overper­formance in the placebo arm, possibly driven by imbalances in prognostic baseline factors.⁴

In my clinical practice, PD-L1 test­ing is performed at diagnosis. The PA­CIFIC regimen may still be used even if tissue is inadequate for testing, since its PFS benefit is independent of PD-L1 expression. Of note, eligibility for the PACIFIC regimen requires that the patient shows no disease progression following CRT.

PACIFIC regimen or HER2-targeted therapy as 1L Tx?
Another question was whether to use the PACIFIC regimen or HER2‑targeted therapy as first-line treatment for our patient, who also harboured an uncommon HER2 exon 20 mutation present in approximately 2–3 percent of NSCLC cases.⁸ Since she had stage III (nonmetastatic) disease, and was relatively young and fit, a more radi­cal treatment with cCRT and immu­notherapy was suggested to improve the chances of survival and achieve a complete response. HER2-targeted therapy was reserved for metastatic disease.

Management of irAEs
As shown in our case, thyroid dis­orders (11.4 percent) and pneumonitis (10.7 percent) were common irAEs. Individual irAEs have different onset windows and can occur at any time.⁹ Regular and continuous monitoring with CT scans, chest X-rays, and blood tests is necessary to detect IrAE.

Overall, the safety profile of durvalumab is manageable.³ Patients should be educated to recognize and report possible AEs promptly.¹⁰ When detected early, most patients with irAEs recover with appropriate treat­ment. Delayed recognition of irAEs at grades 3–4 may necessitate discontin­uation of durvalumab.

Conclusion
In conclusion, both PACIFIC-R and PACIFIC demonstrated encouraging outcomes with durvalumab consolida­tion after CRT in patients with PD-L1 ex­pression <1 percent, supporting the use of durvalumab consolidation in a broad population of patients with unresectable stage III NSCLC who did not have dis­ease progression after CRT.^3,7

Patients with PD-L1 expression <1 percent should not be excluded from durvalumab consolidation, since individual outcomes can still be excel­lent. This is exemplified by our PD-L1– negative case, who initially had a partial response to cCRT and ultimately achieved a complete response with durvalumab consolidation.

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