Maintenance bevacizumab–pemetrexed improves PFS of nonsquamous NSCLC patients
medwireNews: Two studies presented at the 2019 ASCO Annual Meeting show a significant progression-free survival (PFS), but not overall survival (OS), benefit with the addition of pemetrexed to bevacizumab in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC).
Discussant Maurice Pérol (Léon Bérard Cancer Center, Lyon, France) therefore told the audience in Chicago, Illinois, USA, that “pemetrexed is still the preferred maintenance option after a pemetrexed-containing induction regimen, and we do not have any clear evidence to date to use combination maintenance for our patients.”
The Japanese phase III COMPASS trial included 594 treatment-naïve stage IIIB or IV NSCLC patients who were either wild-type for EGFR or harbored uncommon EGFR mutations, and had not progressed after four cycles of induction treatment with carboplatin, pemetrexed, and bevacizumab. They were randomly assigned to receive maintenance bevacizumab 15 mg/kg every 3 weeks, either alone or alongside pemetrexed 500 mg/m2, also given every 3 weeks.
After a median follow-up of 59.9 months, there was no significant difference between the combination and bevacizumab alone groups in the primary endpoint of OS, with comparable median durations of 23.3 and 19.6 months and 2-year rates of 47.8% and 39.5%, respectively.
However, PFS was significantly improved with the combination, at a median of 5.7 months compared with 4.0 months for bevacizumab alone, giving a hazard ratio (HR) for progression or death of 0.67; the corresponding 6-month PFS rates were 47.0% and 31.9%.
Takashi Seto (National Kyushu Cancer Center, Fukuoka), who presented the results on behalf of the COMPASS investigators, speculated that the lack of significance in the OS results could be because the expected median times for the combination and bevacizumab groups were much lower, at a respective 16.5 and 13.0 months, than the observed values.
He noted that subgroup analysis showed a significant OS benefit with bevacizumab–pemetrexed versus bevacizumab alone among patients aged younger than 70 years and those with wild-type EGFR status, but the discussant pointed out that these analyses were univariate and not adjusted for multiplicity.
The phase III ECOG-ACRIN 5508 trial also included previously untreated patients with advanced nonsquamous disease and no progression after four cycles of carboplatin, paclitaxel, and bevacizumab induction. Participants were randomly allocated to receive maintenance therapy every 3 weeks with either bevacizumab 15 mg/kg (n=287), pemetrexed 500 mg/m2 (n=294), or the combination (n=293), and were followed up for a median of 60 months.
Median OS did not differ significantly with either the combination or pemetrexed relative to bevacizumab, at 16.4 and 15.9 months versus 14.4 months.
But again, the addition of pemetrexed to bevacizumab resulted in a significantly longer median PFS versus bevacizumab, at 7.5 and 4.2 months and an HR of 0.67. And there was only a trend towards PFS improvement with pemetrexed alone relative to bevacizumab, with corresponding median times of 5.1 and 4.2 months.
Presenting author Suresh Ramalingam, from the Winship Cancer Institute of Emory University in Atlanta, Georgia, USA, therefore concluded that “monotherapy with either pemetrexed or bevacizumab [is] efficacious as maintenance therapy” in this patient population.
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