Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.
Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer / Miles, D.; Gligorov, J.; Andre, F.; Cameron, D.; Schneeweiss, A.; Barrios, C.; Xu, B.; Wardley, A.; Kaen, D.; Andrade, L.; Semiglazov, V.; Reinisch, M.; Patel, S.; Patre, M.; Morales, L.; Patel, S. L.; Kaul, M.; Barata, T.; O'Shaughnessy, J.; Zhang, Q.; Shao, Z.; Wang, X.; Geng, C.; Yan, X.; Tong, Z.; Shen, K.; Yin, Y.; Sun, T.; Yang, J.; Feng, J.; Yan, M.; Wang, Y.; Liu, Q.; Zhang, S.; De Laurentiis, M.; Santoro, A.; Guarneri, V.; Colleoni, M.; Natoli, C.; Cortesi, L.; Placido, S.; Gianni, L.; Ferrau, F.; Livi, L.; Zambelli, A.; Del Mastro, L.; Tonini, G.; Montemurro, F.; Bianchi, G.; Pedersini, R.; Prete, S.; Allegrini, G.; Naso, G.; Vici, P.; Loirat, D.; Mailliez, A.; Priou, F.; Tredan, O.; Dalenc, F.; Perrin, C.; Timar David, M.; Dohollou, N.; Teixeira, L.; Brocard, F.; Arnaud, A.; Delaloge, S.; Spano, J. -P.; Mansi, L.; Damian, F.; Pedrini, J.; Aleixo, S.; Hegg, R.; Junior, R.; Schmidt, M.; Wenzel, C.; Grischke, E. -M.; Just, M.; Harbeck, N.; Schumacher, C.; Peters, U.; Fischer, D.; Forstbauer, H.; Liersch, R.; Warner, E.; Bouganim, N.; Doyle, C.; Price Hiller, J.; Vandenberg, T.; Pavic, M.; Robinson, A.; Roldan Urgoiti, G.; Califaretti, N.; Alacacioglu, A.; Gumus, M.; Yalcin, B.; Cicin, I.; Kose, F.; Uygun, K.; Kaplan, M.; Cubukcu, E.; Harries, M.; Doval, D.; Gupta, S.; Mohapatra, P.; Chatterjee, S.; Ghadyalpatil, N.; Singhal, M.; Nag, S.; Agarwal, A.; Wolf, I.; Gal Yam, E.; Yerushalmi, R.; Peretz, T.; Fried, G.; Ben Baruch, N.; Katz, D.; Hamilton, E.; Kayali, F.; Brufsky, A.; Telli, M.; Wright, G.; Oyola, R.; Rakowski, T.; Graff, S.; Tjulandin, S.; Aparicio, A.; Ruiz Borrego, M.; Merino, L.; Guerra Martinez, J.; Lopez, E.; Yamashita, T.; Ohtani, S.; Inoue, K.; Ito, Y.; Niikura, N.; Nakayama, T.; Sagara, Y.; Yanagita, Y.; Kamada, Y.; Kaneko, K.; Nervo, A.; Eniu, A.; Schenker, M.; Priester, P.; Melichar, B.; Zimovjanova, M.; Sormova, P.; Sufliarsky, J.; Kakalejcik, M.; Belbaraka, R.; Errihani, H.; Le Than, D.; Pham, D.; Aravantinos, G.; Papadimitriou, C.; Koumakis, G.; Papandreou, C.; Podolski, P.; Tabane, K.. - In: ANNALS OF ONCOLOGY. - ISSN 1569-8041. - 32:8(2021), pp. 994-1004. [10.1016/j.annonc.2021.05.801]
Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer
Yan X.;De Laurentiis M.;Colleoni M.;Cortesi L.;Montemurro F.;Pedersini R.;Naso G.;Gupta S.;Wright G.;
2021
Abstract
Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
