Your criticism of the study I mentioned is reasonable, but in the domain of cancer treatment, a hazard ratio for death (a hard endpoint) of 0.67 is good and, in that sense, if you require much stronger evidence and even better trials you may deprive patients of a useful drug in the meantime. The FDA wants to strike a balance between getting an effective drug to patients as soon as possible and not letting pass ineffective treatments. So, as with most things in life, the kind of evidence I cited is often considered "good enough" even though imperfect.
The evidence for the impact of point mutations can be found in several domains, but the simplest observations comes from hereditary syndromes like Li-Fraumeni. A single change in a nucleotide of the TP53 gene and cancer risk increases to almost 100% in affected individuals. This has been repeatedly observed in many different famliies and also in different syndromes (say, retinoblastoma and RB1 gene). Anyway, the evidence for what is called the "somatic mutation theory" is overwhelming and, despite thoughtful criticism, it is probably accepted as the most plausible theory of carcinogenesis (for the moment!). That's why projects like "Cancer Genome Atlas" get massive funding.
So, yes, point mutations are extremely important. Aneuploidy is also important, but in contrast with a well-described mutation, like the BRAF V600E in melanoma, it does not present an immediate, specific target. As I said, people are working on aneuploidy and maybe something new will come from that, but I don't think it's a "low-hanging fruit".
PS Note that somatic mutations do not exclude aneuploidy and vice versa...