George Simmons (Adam Sandler) is a middle-aged former stand-up comedian turned movie star. Despite his millions he is sad and lonely and most of his recent film work is low-brow and dumb. He is diagnosed with acute myeloid leukemia and offered an experimental treatment that has only an eight-percent chance of therapeutic response. Believing he is about to die, he returns to his roots to do stand-up comedy.
Ira Wright (Seth Rogen) is an aspiring stand-up comedian in his twenties who shares an apartment with his two best friends, Mark and Leo (Jason Schwartzman and Jonah Hill). Mark is a lead in his own TV comedy series and makes good money. Leo is a rising comedy star and guest star or a recurring role on Mark's TV show. George meets Ira at a small comedy club and hires him as his assistant. Ira becomes one of George's only close relationships. The two travel around the country, George hires Ira as his personal assistant and joke writer and opens for him in the big comedy clubs, often meeting with real life comedians who play themselves and talk about the business of comedy.
George reconnects with his ex-fiancĂŠe, Laura (Leslie Mann) who is currently married to Clarke (Eric Bana). Georgeâ˛s physician tells him that the leukemia is in remission. George decides he wants Laura back. Laura invites George and Ira to her house in Marin County while her husband is away on business. George and Ira spend quality time with Laura and her two young daughters. George and Laura sneak off to have sex, but Clarke returns home and there is a huge argument.
The plot of the movie now concerns who Laura will choose, her current husband Clarke whom she suspects has cheated on her (he later confirms he received a happy ending at a massage parlor), or her former boyfriend George (who also cheated on her many times). Ira is not always on George's side in the love triangle, so when it doesn't go George's way in the end, he fires Ira, who then calls George out on having learned nothing from his near-death experience.
Ira returns to his old food-service job. After some time has passed, George attends Ira's stand-up act and sees that his old assistant has become a far more confident performer. The next day, George finds Ira at work and they reconnect as friends, telling each other jokes as equals.

Question: What is the chance the treatment for his disease will be effective?
Answer: 8 percent
Alternative answer: 80%.