ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.

PURPOSE Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) demonstrated survival benefit versus bevacizumab, carboplatin, and paclitaxel (BCP) in chemotherapy-naïve nonsquamous non–small-cell lung cancer (NSCLC). We present safety and patient-reported outcomes (PROs) to provide additional information on the relative impact of adding atezolizumab to chemotherapy with and without bevacizumab in nonsquamous NSCLC. METHODS Patients were randomly assigned to receive atezolizumab, carboplatin, and paclitaxel (ACP), ABCP, or BCP. Coprimary end points were overall survival and investigator-assessed progression-free survival. The incidence, nature, and severity of adverse events (AEs) were assessed. PROs, a secondary end point, were evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 and EORTC QLQ-Lung Cancer 13. RESULTS Overall, 400 (ACP), 393 (ABCP), and 394 (BCP) patients were safety evaluable (ie, intention-to-treat population that received one or more doses of any study treatment). More patients had grade 3/4 treatment-related AEs during the induction versus maintenance phase (ACP, 40.5% v 8.2%; ABCP, 48.6% v 21.2%; BCP, 44.7% v 11.1%). During induction, the incidence of serious AEs (SAEs) was 28.3%, 28.5%, and 26.4% in the ACP, ABCP, and BCP arms, respectively. During maintenance, SAE incidences were 20.0%, 26.3%, and 13.0%, respectively. Completion rates of the PRO questionnaires were > 88% at baseline and remained ≥ 70% throughout most study visits. Across arms, patients on average reported no clinically meaningful worsening of global health status or physical functioning scores through cycle 13. Patients across arms rated common symptoms with chemotherapy and immunotherapy similarly. CONCLUSION ABCP seems tolerable and manageable versus ACP and BCP in first-line nonsquamous NSCLC. Treatment tolerability differed between induction and maintenance phases across treatment arms. PROs reflect a minimal treatment burden (eg, health-related quality of life, symptoms) with each regimen.

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8501 Background: Non-small cell lung cancer (NSCLC) is incurable in most patients with locally advanced stage IIIA disease. Previous results indicate that the use of neoadjuvant chemoimmunotherapy could increase the percentage of cured patients being a promising therapeutic option that has to be tested in randomized clinical trials. Methods: NADIM II (NCT03838159) is an open-label, randomized, two-arm, phase II, multi-center clinical trial. Patients with resectable clinical stage IIIA (per AJCC 7th ed) NSCLC, ECOG PS 0-1, and no known EGFR/ALK alterations were randomized to receive Nivolumab (NIVO) 360mg + Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) as neoadjuvant treatment followed by surgery, or Paclitaxel 200mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/- 3 days) followed by surgery. Patients with R0 resection confirmed by pathological evaluation initiated adjuvant administration of NIVO within the 3rd to 8th week (+7 days) from surgery and for 6 months. The primary endpoint was pathological complete response (pCR) by blinded independent pathological review (BIPR) in the intent-to-treat population (ITT). pCR was defined as 0% viable tumor cells in resected lung and lymph nodes; patients who did not undergo surgery were classified as non-responders. Major pathological response (MPR; ≤ 10% viable tumor) per BIPR, overall response rate (ORR), toxicity profile, and potential predictive biomarkers are secondary endpoints. Results: Between February 8, 2019, and November 11, 2021, 90 patients were enrolled, of whom 87 patients were valid. Neoadjuvant NIVO + chemo significantly increased the pCR rate compared to chemo in the ITT (36.2% vs 6.8%; Relative Risk (RR) 5.25 [99% CI 1.32-20.87]; P = 0.0071). NIVO + chemo also improved MPR rates vs chemo in the ITT (52 % vs 14 %), as well as ORR (74 % vs 48%). Definitive surgery occurred for 91% of pts treated with NIVO + chemo and 69% with chemo; surgery was cancelled rarely due to AEs (1 pts/experimental arm) and due to disease progression in 1 and 4 pts in the experimental and control arm respectively. Grade 3-4-related AEs were reported in 24 % vs 10% in the NIVO + chemo vs chemo arms, respectively. In the ITT experimental arm, patients with pCR had higher PD-L1 TPS (median 70%, IQR 5-90%) compared to non-responders (median 0%, IQR 0-37.5%, P = 0.0035). AUC to predict pCR was 0.734 (95% CI 0.59-0.88; P = 0.005). The pCR rate rises across increasing categories of PD-L1 TPS ( < 1% 14.3%; 1-49% 41.7%; ≥50% 61.1%; P = 0.008). Conclusions: This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. Thus, this treatment should become the standard of care in these patients. Clinical trial information: NCT03838159.