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The PACIFIC trial showed that administration of maintenance Durvalumab in patients with stage III non small cell lung cancer (NSCLC) after chemo-radiotherapy (CRT) resulted in an increased overall survival: 42.9 versus 33,4 months at 5 years. However, in Europe, drug reimbursement is provided only in patients with PD-L1 expression higher than 1%. Recent studies have shown a significant up-regulation of PD-L1 and CD8+ expression on tumor cells after chemotherapy, both radiotherapy and chemotherapy being able to induce an increase in PD-L1 expression due to their ability to induce DNA damage. The main purpose of this multicenter retrospective study is to evaluate the variation in PD-L1 expression before and after chemo-radiation treatment in patients with unresecable stage III NSCLC. Secondary objective are: Impact of the re-determination of PD-L1 expression on the therapeutic process approach (possibility of administering maintenance Durvalumab), acute complications of the rebiopsy.

Thirty-one patients with unresecable stage III NSCLC, PDL1 negative at onset, who underwent CRT and subsequently re-biopsied to re-determinate PDL1 status were enrolled by 20 Italian center. Pre- and post CRT histological samples were centralized in a single laboratory for the review of PD-L1 expression. The percentage of patients undergoing Durvalumab after CRT, the percentage of non-diagnostic procedures, the acute complications of re-biopsy were investigated

The results of this study are still preliminary and complete analysis was archived in 7 patients. Median age was 68.2 months. All patients received radiotherapy treatment for a total dose of 60 Gy concomitant with cisplatin-based chemotherapy. The average time between the end of the CRT treatment and the start of Durvalumab was 54.6 months. Of all the patients analyzed, 2 currently showed a PDL1 expression switch with weak positivization (1% and 2% respectively) and this gave the opportunity to start Durvalumab maintenance treatment, while in the other cases the negative result was confirmed at the re-biopsy. Of the 2 patients with PDL1 positivization one developed disease progression and second-line chemotherapy was administered, while the second had a partial response and is continuing maintenance treatment. The re-biopsy procedure was well tolerated, however one patient experienced severe hypoxia requiring hospitalization, with recovery after two weeks

Although the data analysis is still ongoing, the present study is the first work in the literature evaluating the re-determination of PDL1 after CRT. The positivization of PDL1 after CRT is not a frequent event and could be burdened with severe rare side effects, however it guarantees an important therapeutic chance that can influence the overall survival of these patients. So, despite the results it is appropriate to discuss and identify in multidisciplinary board the patients who may be susceptible to re-biopsy