The 41-year-old called into the show on Monday along with her Sex Tape costar Jason Segel to talk about their new film.
When host Jackie O mentioned that the duo's onscreen daughter in the flick reminded her a little bit of Drew Barrymore's character in ET, Cameron said: "Aw, yeah! She does, now that you mention it. And she's as bright and lively as Drew is, as well. She's a sweet little girl."
While the Aussie radio hosts should have probably left it there, Kyle took it upon himself to add: "Let's hope she misses out on the Drew Barrymore drug years, because those were a great thing to watch, but not so good to be in, I'd imagine."
Cue awkward silence.
Jackie attempted to break the tension, quipping: "What doesn't kill you makes you stronger." But it was too little too late.
"I'm sure, Kyle, you've never been through a drug phase, have you? Or alcoholism or anything like that? Pretty clean... always did it right? Congratulations," the actress responded before announcing they had to "go now" and hanging up the phone.
Following the interview Jackie slammed Kyle for his slightly, er, careless comment. "Good one, Kyle," she said. "You ruined that interview... you brought up Drew Barrymore, her best friend's drug addiction in the past. She's her best friend!"
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