Metastatic TNBC patients treated with PBCT tended to have a higher response rate, without a significant improvement of PFS or OS, compared with other subtypes. Toxicity was acceptable. Longer observation and further analysis are warranted.

Figure 1. Evidence of rapid tumor regrowth following bevacizumab cessation, within 1 month, with accelerated kinetics in patient 2 (A) before first BV treatment, (B) during first BV treatment, before surgery, (C) 1 month after colon and liver surgery and (D) during second BV treatment, after surgery.

659MOAvelumab (A) as the basis of neoadjuvant chemotherapy (NAC) regimen in platinum eligible and ineligible patients (pts) with non-metastatic muscle invasive bladder cancer (NM-MIBC)

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4517 Background: Nearly half of the patients (pts) diagnosed with non-metastatic muscle invasive bladder cancer are unfit for cisplatin therapy and no alternative options of neoadjuvant treatment exist. Avelumab (A), a monoclonal antibody directed against PD-L1, showed efficacy in advanced urothelial cancer. We report preliminary data assessing preoperative avelumab associated with paclitaxel and gemcitabine or avelumab alone in the cisplatin ineligible cohort. The results of the cisplatin eligible cohort were reported at ESMO 2021. Methods: AURA is a prospective, multicenter, randomized, phase II trial for pts with cT2-4aN0-2M0 bladder carcinoma. Pts were enrolled in two separated cohorts based on eligibility for cisplatin chemotherapy. Cisplatin ineligible pts received 4 cycles of paclitaxel-gemcitabine (PG) plus A every 2 weeks or 4 cycles of A every 2 weeks (1:1). Primary endpoint was pCR rate (ypT0/isN0) with the objective, in each arm, to show pCR rate > 5% (90% power reached in case of pCR rate > 25%). Two-step design was used with planned interim analysis after 12 evaluable pts per arm. Secondary endpoints were pathologic downstaging rate ( < ypT2N0) and safety. Results: A total of 56 cisplatin-ineligible pts were evaluable. For PG + A arm (n = 28): median age was 72 years (41-80), 93% male. For A alone arm (n = 28): median age was 75 years (49-89), 93% male. One patient did not undergo surgery due to progression in the A arm but was included in intention to treat analysis. Five pts did not receive the 4 cycles of treatment; reasons included toxicity (n = 3) for PG + A arm and patient/physician decision (n = 2) for A arm. pCR was achieved in 5 pts (18%; 95%CI 6%-37%) treated with PG + A and 10 pts (36%; 95%CI 19%-56%) treated with A. Downstaging to < ypT2N0 was achieved in 6 pts (21%; 95%CI 8%-41%) and 11 pts (39%; 95%CI 22%-59%), respectively. Median time from treatment initiation to surgery was 82 days (55-144) for PG + A arm and 67 days (38-89) for A arm. Most common irAEs of any grade were asthenia (15%), skin toxicity and myalgia/arthralgia (each 5%). There were 2 pts in the PG + A arm with grade 3 irAEs (hepatitis and pneumonitis) that caused A discontinuation for 1 patient. No treatment-related deaths were reported. Conclusions: Neoadjuvant single agent avelumab resulted in high pCR and was safely administered without compromising surgical resection. Our results suggest that the addition of taxane-gemcitabine regimen to avelumab may reduce avelumab efficacy with low pCR rate. Survival analysis and correlative studies are underway. Clinical trial information: NCT03674424.

Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world. Vinorelbine is an active vinca-alkaloid with a broad spectrum of anti-tumour activity. In particular, it has high activity in NSCLC, where a synergy with cisplatin has been demonstrated. Recently, oral vinorelbine has shown a similar activity and efficacy as compared to the intravenous formulation, giving to the patient an easier way of administration and increasing his comfort. Although surgery remains the best chance of cure for patients with resectable NSCLC, it is now accepted that postoperative cisplatin-based adjuvant chemotherapy significantly improves survival in patients with NSCLC. The combination of cisplatin and vinorelbine is the most active among all the adopted schedules. Patients presenting with locally advanced disease at diagnosis benefit from concomitant chemotherapy with cisplatin-vinorelbine regimen in combination with thoracic radiotherapy. Platinum-based combinations have become the standard of care for treating NSCLC. Vinorelbine–cisplatin combination is one of the proposed doublets for treating advanced, metastatic, NSCLC. Because of its favorable toxicity profile, vinorelbine has become a major compound as a treatment for elderly patients with advanced NSCLC.

Introduction Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies. Methods and analysis Oncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety. Ethics and dissemination The study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals. Trial registration number ClinicalTrials.gov (NCT03674424).

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